Patent application title: Materials and methods for assaying for methylation of CpG islands associated with genes in the evaluation of cancer
Inventors:
Wadiha Freije (Forest Park, IL, US)
Deborah Nusskern (Forest Park, IL, US)
Assignees:
EUCLID DIAGNOSTICS LLC
IPC8 Class: AC12Q168FI
USPC Class:
435 6
Class name: Chemistry: molecular biology and microbiology measuring or testing process involving enzymes or micro-organisms; composition or test strip therefore; processes of forming such composition or test strip involving nucleic acid
Publication date: 2008-09-04
Patent application number: 20080213791
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Patent application title: Materials and methods for assaying for methylation of CpG islands associated with genes in the evaluation of cancer
Inventors:
Wadiha Freije
Deborah Nusskern
Agents:
LEYDIG VOIT & MAYER, LTD
Assignees:
EUCLID DIAGNOSTICS LLC
Origin: CHICAGO, IL US
IPC8 Class: AC12Q168FI
USPC Class:
435 6
Abstract:
Provided are methods, reagents, and kits for evaluating cancer, such as
prostate cancer, in a subject. Disclosed methods of evaluating cancer
include methods of diagnosing cancer, methods of prognosticating cancer
and methods of assessing the efficacy of cancer treatment. The methods
include assaying a biological sample for methylation of a CpG island
associated with specified genes. Provided reagents and kits include
primers suitable for amplifying at least a portion of a target CpG
islands associated with specified genes.Claims:
1. A method of detecting the methylation status of one or more CpG islands
indicative of cancer, which method comprises:providing a biological
sample from a subject in need of cancer evaluation; andassaying the
biological sample for methylation of a CpG island associated with at
least one gene selected from the group consisting of neuregulin
cell-surface ligand (NRG1), kinesin family member 13B (KIF13B),
adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface
receptor (GFRA2), RET proto-oncogene (RET), G-protein-coupled protein
receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3),
paladin (predicted protein tyrosine phosphatase) (PALD),
methyltransferase family member 1 (HEMK1), fibroblast growth factor 4
oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1A),
ring finger protein 180 (RNF180), EGFR-co-amplified and overexpressed
(DKFZP564K0822 or ECOP), zinc finger protein 596 (ZNF596), similar to 7
transmembrane helix receptor (LOC441320), L-threonine dehydrogenase
(TDH), hypothetical protein C8orf79 (C8orf79/FLJ36980), fibroblast growth
factor receptor 20 (FGF20), EF-hand domain family member 2A
(LOC286097/EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1
(ASAH1), nodal homolog (NODAL), hypothetical protein similar to zinc
finger protein 532 (LOC399783), transcription factor LIM homeodomain
(ISL2), matrix metallopeptidase 9 (MMP9), leucine rich repeat containing
49 (LRRC49), tumor necrosis factor (ligand) superfamily member 11
(TNFSF11), ras homolog gene family member D (RHOD), Kinesin family member
C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor
protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione
peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix
metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11
(TNFSF11), ras homolog gene family member D (RHOD), and leucine rich
repeat containing 49 (LRRC49), wherein methylation of the assayed CpG
island is indicative of cancer.
2. A method of detecting the methylation status of one or more CpG islands indicative of prostate cancer, which method comprisesproviding a biological sample from a male mammal in need of prostate cancer evaluation; andassaying the biological sample for methylation of a CpG island associated with at least one gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), kinesin family member 13B (KIF13B), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), flbroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671 or RNF180), EGFR-co-amplified and overexpressed (DKFZP5640822 or ECOP), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-.beta. signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), and transcription factor LIM homeodomain (ISL2), matrix metallopeptidase 9 (MMP9), leucine rich repeat containing 49 (LRRC49), tumor necrosis factor (ligand) superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), Kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), Ras association (RalGDS/AF-6) domain family 5 (RASSF5), and HtrA serine peptidase 4 (HTRA4); andoptionally, further assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be methylated in prostate cancer and that is known not to be detectably methylated or methylated at a lower level in benign prostate hyperplasia (BPH); wherein methylation of the assayed CpG island or islands is indicative of prostate cancer.
3. The method of claim 2, wherein the method comprises:assaying the biological sample for methylation of CpG islands associated with at least three genes, at least one of the genes being selected from the group consisting of neuregulin cell-surface ligand (NRG1), kinesin family member 13B (KIF13B), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671 or RNF180), EGFR-co-amplified and overexpressed (DKFZP5640822 or ECOP), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097 or EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-.beta. signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), and transcription factor LIM homeodomain (ISL2);the CpG island associated with a gene that is known to be methylated in prostate cancer is also known to be not methylated in BPH or methylated at a level of about 10% or less in BPH; andwherein methylation of the CpG islands associated with the at least three genes is indicative of prostate cancer;
4. The method of claim 2, wherein the at least one CpG island that is known to be methylated in prostate cancer and that is known to be unmethylated or methylated at a lower level in BPH is or includes one or more CpG island associated with glutathione S-transferase P1 (GSTP1), glutathione peroxidase 3 (GPX3), glutathione S-transferase M1 (GSTM1), Cub and Sushi multiple domains1 (CSMD1), tumor necrosis factor receptor superfamily member 10C (TNFRSF10C), tumor necrosis factor receptor superfamily 10D (TNFRSF10D), secreted frizzled-related protein 1 (SFRP1), secreted frizzled-related protein 2 (SFRP2), dickkopf homolog 3 (DKK3), prostaglandin-endoperoxide synthase 2 (PTGS2), cyclin-dependent kinase inhibitor 1C (CDKN1C/p57), Ras association (RalGDS/AF-6) domain family 1 (RASSF1), G-protein coupled receptor 62 (GPR62).
5. The method of claim 4, wherein the at least one CpG island that is known to be methylated in prostate cancer and that is known to be unmethylated or methylated at a lower level in BPH is or includes one or more CpG island associated with glutathione S-transferase P1 (GSTP1).
6. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 4 genes.
7. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 5 genes.
8. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 6 genes.
9. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 7 genes.
10. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 8 genes.
11. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 9 genes.
12. The method of claim 1, wherein the assaying for methylation of a CpG island comprises amplifying a target sequence that includes at least one CpG dinucleotide in a target sequence selected from the group consisting of (a) SEQ ID NO: 1 and 2 [NRG1], SEQ ID NO: 3 and 4 [ADRB3], SEQ ID NO: 5 and 6 [GFRA2], SEQ ID NO: 7 and 8 [KIF13B], SEQ ID NO: 9 and 10 [RET], SEQ ID NO: 11 and 12 [GPR147], SEQ ID NO: 13 and 14 [NEUROG3], SEQ ID NO: 15 and 16 [PALD], SEQ ID NO: 17 and 18 [HEMK1], SEQ ID NO: 19 and 20 [FGF4], SEQ ID NO: 21 and 22 [GPR62], SEQ ID NO: 23 and 24 [HTR1A], SEQ ID NO: 25 and 26 [RNF180], SEQ ID NO: 27 and 28 [DKFZP5640822], SEQ ID NO: 29 and 30 [ZNF596], SEQ ID NO: 33 and 34 [LOC441320], SEQ ID NO: 35 and 36 [TDK], SEQ ID NO: 37 and 38 [FLJ36980], SEQ ID NO: 39 and 40 [FGF20], SEQ ID NO: 41 and 42 [EFHA2], SEQ ID NO: 43 and 44 [ASAH1], SEQ ID NO: 49 and 50 [NODAL], SEQ ID NO: 51 and 52 [LOC399783], SEQ ID NO: 53 and 54 [ISL2] and (b) fully or partially methylated derivatives of (a).
13. The method of claim 1, wherein the assaying for methylation of a CpG island comprises amplifying a target sequence that includes at least one CpG dinucleotide or a deaminated derivative thereof in a target sequence selected from the group consisting of (a) SEQ ID NOS: 119 and 220 [KIFC2], SEQ ID NOS: 121 and 122 [C20ORF23], SEQ ID NOS: 123 and 124 [GFRA1], SEQ ID NOS: 129 and 130 [DKK2], SEQ ID NOS: 135 and 136 [NTN1], SEQ ID NO: 195 [RHOD], SEQ ID NO: 196[TNFSF11], SEQ ID NO: 197 [MMP9], and SEQ ID NO: 198 [LRRC49] (b) fully or partially methylated cytosine derivatives of (a), and (c) deaminated derivatives of (b).
14. The method of claim 2, wherein the assaying for methylation of a CpG island comprises amplifying a target sequence that includes at least one CpG dinucleotide or a deaminated derivative thereof in a target sequence selected from the group consisting of (a) SEQ ID NOS: 119 and 220 [KIFC2], SEQ ID NOS: 121 and 122 [C20ORF23], SEQ ID NOS: 123 and 124 [GFRA1], SEQ ID NOS: 129 and 130 [DKK2], SEQ ID NOS: 135 and 136 [NTN1], SEQ ID NOS: 133 and 134 [RASSF5] and SEQ ID NOS: 193 and 194 [HTRA4], (b) fully or partially methylated cytosine derivatives of (a), and (c) deaminated derivatives of (b).
15. The method of claim 12, wherein the assaying for methylation comprises performing terminator-coupled linear amplification in the presence of at least one dideoxynucleotide and determining the size of the amplified fragments to thereby determine the methylation status of the cytidine residues.
16. The method of claim 15, wherein the assaying comprises performing linear amplification in the presence of only one dideoxynucleotide.
17. The method of claim 15, wherein the assaying comprises performing linear amplification in the presence of only two dideoxynucleotides.
18. The method of claim 15, wherein the at least one dideoxynucleotide is chosen from the group consisting of dideoxyadenine, dideoxcytidine, dideoxguanine, and dideoxthymidine.
19. A terminator-coupled linear amplification method of determining the methylation status of a CpG island, wherein the method comprises(a) providing a DNA sample;(b) incubating the DNA sample under deaminating conditions to thereby produce a deaminated DNA sample;(c) optionally, purifying the deaminated DNA sample;(d) amplifying a target sequence or target sequences that include one or more CpG islands or portions of one or more CpG islands to thereby produce one or more amplified target sequences;(e) optionally, purifying the one or more amplified target sequences;(f) linearly amplifying the one or more amplified target sequences of step (d) or (e) in the presence of a primer and 1 to 3 dideoxynucleotides to generate one or more fragments of different lengths, wherein each length corresponds to the distance in bases from the 5' end of the primer to the position where the dideoxynucleotide was incorporated;(g) optionally, purifying the one or more fragments; and(h) analyzing the one or more fragments to determine their lengths and thereby determine the methylation status of methylated cytosines within the one or more amplified target sequences.
20. A pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49).
21. A set of primers comprising:(i) at least one pair of primers of claim 20; and(ii) at least one pair of primers suitable for amplifying at least a portion of a CpG island associated with at least one other gene that is known to be methylated in prostate cancer but not methylated or methylated at a low level in BPH.
22. A set of primers comprising:(i) a first pair of primers of claim 20; and(ii) a second pair of primers of claim 20, wherein the second pair of primers is suitable for amplifying at least a portion of a different CpG island than the first pair of primers.
23. The set of primers of claim 22, wherein the CpG island amplified by the first pair of primers is associated with a first gene, the CpG island amplified by the second pair of primers is associated with a second gene, and the first and second genes are different genes.
24. The set of primers of claim 21, wherein the set further comprises a third pair of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), flbroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer but not methylated or methylated at a low level in BPH, wherein the third pair of primers is suitable for amplifying a different CpG island than that suited for amplification by the first or second pair of primers.
25. The set of primers of claim 24, wherein the set further comprises a fourth pair of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer but not methylated or methylated at a low level in BPH, wherein the third pair of primers is suitable for amplifying a different CpG island than that suited for amplification by the first, second, or third pair of primers.
26. The set of primers of claim 25, wherein the set further comprises a fifth pair of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), flbroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), flbroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer but not methylated or methylated at a low level in BPH, wherein the third pair of primers is suitable for amplifying a different CpG island than that suited for amplification by the first, second, third, or fourth pair of primers.
27. The set of primers of claim 26, wherein the set further comprises a sixth pair of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), flbroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer, wherein the fourth pair of primers is suitable for amplifying a different CpG island than that suited for amplification by the first, second, third, fourth or fifth pair of primers.
28. The set of primers of claim 27, wherein the set further comprises from one to four additional pairs of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer, wherein each pair of primers in the set amplifies a different CpG island.
29. The set of primers of claim 28, wherein the set further comprises one or more additional pairs of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), flbroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), flbroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer, wherein each pair of primers in the set amplifies a different CpG island.
30. A pair of primers or set of primers of claim 20, wherein the pair or set of primers have sequences selected from the group consisting of SEQ ID NOs: 55 to 118.
31. The primer or set of primers of claim 20, wherein the pair of primers or the set of primers includes two primers suitable for amplifying a CpG island associated with NRG1 or KIF13b.
32. The primer or set of primers of claim 20, wherein the pair of primers or the set of primers includes two primers suitable for amplifying a CpG island associated with TDH, ASAH1, FGF20, HEMK1, PALD NEUROG, EFHA2, KIFC2, GFRA1, DKK2, TNFSF11, NTN1, or RHOD.
33. A kit for detecting the methylation status of a CpG island indicative of cancer, the kit comprising:(i) a pair of primers or set of primers of claim 20; and(ii) instructions for using the primers to amplify at least one CpG island from a biological sample.
34. The kit of claim 33, further comprising a buffer selected from the group consisting of (a) a buffer for amplifying genomic DNA, (b) a buffer for preparing genomic DNA from a biological sample, and (c) a buffer for preparing genomic DNA from plasma or urine.
Description:
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001]This patent application is a continuation of International Patent Application No. PCT/US2006/060685, filed Nov. 8, 2006, designating the United States, which claims the benefit of U.S. Provisional Patent Application No. 60/734,577, filed Nov. 8, 2005, which are incorporated by reference herein in their entirety.
INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ELECTRONICALLY
[0002]Incorporated by reference in its entirety herein is a computer-readable nucleotide/amino acid sequence listing submitted concurrently herewith and identified as follows: One 214,875 Byte ASCII (Text) file named "702375_ST25.TXT," created on May 2, 2008.
BACKGROUND OF THE INVENTION
[0003]Phosphate linked cytosine-guanine (CpG) dinucleotides are statistically underrepresented in the genomes of higher eukaryotes, including mammals. The dinucleotide is reportedly found at only 5-10% of its predicted frequency. The majority of CpG dinucleotides that do remain in the human genome are normally located within repetitive sequences that are characterized by low gene expression levels and exhibit methylation at the cytosine residues.
[0004]CpG islands, on the other hand, represent genomic sequences that contain clusters of CpG dinucleotide. CpG islands may be associated with the promoter region or 5' end of coding sequences or may be present within introns or in genomic regions that are not known to be associated with coding sequences. They may be unmethylated or methylated in normal tissues and the methylation pattern may be used to control tissue specific expression and the expression of imprinted genes. Methylation of CpG islands within promoter regions can result in the downregulation or silencing of the associated gene. An increase in methylation of normally unmethylated islands is observed in aging tissues even as the overall methylcytosine content of the DNA is reduced. The aberrant methylation pattern is more pronounced in cancer cells with increased methylation or hypermethylation detected in various cancer tissues. CpG islands may be methylated to varying densities within the same tissue. Thus, aberrant methylation of cytosines within CpG islands can be a primary epigenetic event that acts to suppress the expression of genes involved in critical cellular processes, such as DNA damage repair, hormone response, cell-cycle control, and tumor-cell adhesion/metastasis, leading to tumor initiation, progression and metastasis (Li et al., Biochim. Biophys. Acta, 1704: 87-102 (2004)). It has been proposed that a unique profile of promoter hypermethylation exists for each human cancer in which some gene changes are shared and other gene changes are cancer-type specific (Esteller et al., Cancer Res., 61: 3225-3229 (2001)). Given that aberrant methylation represents new information not normally present in genomic DNA and that aberrant methylation is a common DNA modification and affects a large number of genomic targets, it is feasible to develop diagnostic and prognostic tests based on information obtained from multiple target CpGs. Such tests may be based on CpGs that are aberrantly hypermethylated or hypomethylated in the diseased tissues. They may also be based on changes in methylation density in CpG islands as long as the changes corrolate with the presence of cancer.
[0005]Prostate cancer, for example, which is the most common malignancy and the second leading cause of death among men in the U.S. (Li et al. (2004), supra), has been found to be associated with the methylation of CpG islands in the promoters of over 30 genes, in particular the CpG island of the glutathione S-transferase P1 (GSTP1) gene. GSTP1 methylation has been detected in over 50% of DNA recovered from urine and plasma of prostate cancer patients (Goessl et al., Ann. N.Y. Acad. Sci., 945: 51-58 (2001); Cairns et al., Clin. Cancer Res., 7: 2727-2730 (2001); Jeronimo et al., Urology, 60: 1131-1135 (2002); and Gonzalgo et al., Clin. Cancer Res., 9: 2673-2677 (2003)). However, if diagnosis of prostate cancer relied solely on the detection of the methylation of the CpG island in the GSTP1 gene, the theoretical limit of the sensitivity of such a test would only be approximately 90%. GSTP1 is also methylated in prostatic intraepithelial lesions (PIN) which may lead to a false positive diagnosis. Some CpG islands are methylated in prostate cancer and other diseases of the prostate, such as benign prostatic hyperplasia (BPH). They may even exhibit some degree of methylation in normal aging prostates. Such markers may not be suitable individually for prostate cancer diagnosis. Therefore, a panel of markers is required to achieve the sensitivity and specificity needed for a clinical test.
[0006]The prostate-specific antigen or PSA test continues to be widely used in the early detection of prostate cancer. While the PSA test has resulted in the majority of prostate cancer cases being diagnosed in asymptomatic men (Mettlin et al., Cancer, 83(8): 1679-1684 (1998a); Mettlin et al., Cancer, 82(2): 249-251 (1998b); Humphrey et al., J. Urol., 155: 816-820 (1996); and Grossfeld et al., Epidemiol. Rev., 23(1): 173-180 (2001)), the PSA test suffers from poor specificity, which can be as low as 33% when a PSA cut-off level of 2.6 ng/ml is used (Thompson et al., N. Engl. J. Med., 350: 2239-2246 (2004)), even though the sensitivity can be as high as 83%. The poor specificity of the PSA test is a direct result of increased secretion of PSA in other diseases of the prostate, such as BPH and prostatitis. Thus, an elevated PSA level indicates the need for additional screening in the form of needle biopsy. Ultimately, the results of needle biopsies lead to the diagnoses of prostate cancer.
[0007]Over 1 million needle biopsies of prostates are performed each year at a cost of about $1,500 each and much discomfort to the patient. However, less than 200,000 of these result in a diagnosis of prostate cancer. Therefore, the majority of needle biopsies are being performed needlessly.
[0008]In view of the above, there is a need for non-invasive methods of diagnosing and prognosticating cancer, such as prostate cancer, that reduce the cost and suffering associated with currently available cancer screening methods. It is an object of the invention to provide materials and methods for non-invasive diagnosis and prognosis of cancer, such as prostate cancer. This and other objects and advantages, as well as additional inventive features, will become apparent from the detailed description provided herein.
BRIEF SUMMARY OF THE INVENTION
[0009]The invention provides materials and methods for evaluating cancer. Methods of evaluating can include methods of diagnosing and prognosticating cancer as well as methods of assessing the efficacy of cancer treatment. Generally, the methods provided involve assaying for methylation of CpG islands associated with specific genes. The invention also provides pairs of isolated or purified primers that can be used in the methods of the invention, for example, to amplify and/or detect the methylation state of the CpG islands associated with specific genes. The invention also provides kits comprising one or more pairs of primers useful in the disclosed methods.
[0010]The invention provides methods of diagnosing cancer by assaying for one or more methylated CpG islands that are indicative of cancer. Generally, the method comprises providing a biological sample from a subject in need of cancer diagnosis and assaying the sample for methylation of one or more CpG islands associated with at least one gene selected from the group consisting of: neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidyl-inositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (predicted protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1A), ring finger protein 180 (LOG 285671 or RNF180), EGFR-co-amplified and overexpressed (DKFZP564K0822 or ECOP), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC286097 or EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-β signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2) Kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49).
[0011]The invention also provides a method of diagnosing prostate cancer in a male mammal by assaying for one or more methylated CpG islands that are indicative of prostate cancer. The method can include providing a biological sample from a subject in need of cancer diagnosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, ECOP, ZNF596, LOC441320, TDH, FLJ36980, EFHA2, ASAH1, NODAL, LOC399783, ISL2, MMP9, TNFSF11, RHOD or LRRC49. Kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), Ras association (RalGDS/AF-6) domain family 5 (RASSF5), and HtrA serine peptidase 4 (HTRA4). Optionally, the method of diagnosing prostate cancer can also include assaying for methylation of one or more CpG island associated with at least one gene that is known to be methylated in prostate cancer but is known not to be detectably methylated or is methylated at a lower level (e.g., about 50% or less, about 40% or less, 30% or less, about 20% or less, or about 10% or less) in BPH.
[0012]The invention also provides methods of prognosticating cancer by assaying for the methylation of one or more genes that are indicative of the grade or stage of the cancer, and/or the length of disease-free survival following treatment for cancer. Generally, the method comprises providing a biological sample from a subject in need of cancer prognosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD and LRRC49.
[0013]Further provided by the invention is a method of prognosticating prostate cancer in a male mammal by assaying for one or more methylated CpG islands that are indicative of the grade or stage of prostate cancer, and/or the length of disease-free survival following treatment of prostate cancer. The method comprises providing a biological sample from the male mammal and assaying the sample for methylation of a CpG island associated with at least one of the following genes: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, GPR62, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD or LRRC49. Optionally, the method of prognosticating prostate cancer can also include assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be methylated in prostate cancer but is known not to be detectably methylated or is methylated at a lower level (e.g., about 50% or less, about 40% or less, 30% or less, about 20% or less, or about 10% or less) in BPH. Methylation of the CpG islands associated with the genes is indicative of the grade or stage of the cancer, and/or the length of disease-free survival following treatment.
[0014]Furthermore, the invention provides methods of assessing the efficacy of treatment of cancer by assaying for the reduced methylation of CpG islands that indicates efficacy of treatment. Generally, the method comprises providing a first and a second biological sample from a subject in need of assessing the efficacy of treatment of cancer and assaying the samples for a change in methylation level of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD and LRRC49. The first biological sample is taken before the second biological sample, and the second biological sample is taken during or after a course of treatment. A decrease or absence of methylation of the assayed one or more CpG islands in the second sample (i.e., following the course of treatment) indicates that the treatment is effective. Alternatively, the maintenance or increase of methylation in the assayed CpG islands in the second sample can indicate a reduction or absence of treatment efficacy.
[0015]Also provided is a method of assessing the efficacy of treatment of prostate cancer in a male mammal by assaying biological samples, which are taken from the male mammal periodically during the course of treatment, for methylation of a CpG island and wherein a decrease or absence of methylation of the CpG islands following the course of treatment indicates that the treatment is effective. The method comprises (a) providing a first and a second biological sample from a subject undergoing a course of cancer treatment, wherein the first sample is taken at an earlier time than the second sample, and the second sample is taken during or following a course of treatment and (b) assaying the samples for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD and LRRC49. Optionally, this method can also include assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be methylated in prostate cancer but is known not to be detectably methylated or is methylated at a lower level (e.g. about 50% or less, about 40% or less, 30% or less, about 20% or less, or about 10% or less in BPH.
[0016]In preferred embodiments, the aforementioned methods of diagnosing, prognosticating and assessing the efficacy of treatment of cancer can further include assaying the biological sample for methylation of multiple CpG islands, for example, CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more genes.
[0017]Additionally, the invention provides a terminator-coupled linear amplification method of determining the methylation status of a CpG island. Generally, the method includes providing a DNA sample for terminator-coupled linear amplification and then incubating the DNA sample under deaminating conditions to thereby produce a deaminated DNA sample. Optionally, the deaminated DNA sample can be purified. The deaminated sample is used as template to amplify a target sequence or target sequences that include one or more CpG islands or portions of one or more CpG islands thereby producing one or more amplified target sequences. Optionally, the one or more amplified target sequences are purified. One or more sequences in the amplified target sequences are linearly amplified in the presence of a primer and a dideoxynucleotide to generate one or more fragments of different lengths, wherein each length corresponds to the distance in bases from the 5' end of the primer to the position where the dideoxynucleotide is incorporated. Optionally, the one or more fragments is purified. The one or more fragments are analyzed to determine their lengths. The lengths of the fragments can be used to determine the methylation status of methylated cytosines within the one or more amplified target sequences.
[0018]The invention also provides pairs of primers suitable for amplifying a CpG-island associated with genes described herein. Primers can include isolated or purified nucleic acid molecules suitable for amplifying a CpG island containing target sequence. Target sequences can include genomic sequence that has been fully methylated and fully deaminated such as those in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, and SEQ ID NO: 54.
[0019]Exemplary primer pairs include SEQ ID NOS: 55 and 56, SEQ ID NOS: 57 and 58, SEQ ID NOS: 59 and 60, SEQ ID NOS: 61 AND 62, SEQ ID NOS: 63 and 64, SEQ ID NOS: 65 and 66, SEQ ID NOS: 67 and 68, SEQ ID NOS: 69 and 70, SEQ ID NOS: 71 and 72, SEQ ID NOS: 73 and 74, SEQ ID NOS: 77 and 78, SEQ ID NOS: 79 and 80, SEQ ID NOS: 81 and 82, SEQ ID NOS: 83 and 84, SEQ ID NOS: 87 and 88, SEQ ID NOS: 89 and 90, SEQ ID NOS: 91 and 92, SEQ ID NOS: 93 and 94, SEQ ID NOS: 95 and 96, SEQ ID NOS: 97 and 98, SEQ ID NOS: 103 and 104, SEQ ID NOS: 105 and 106, SEQ ID NOS: 107 and 108, SEQ ID NOS: 109 and 110, SEQ ID NOS: 111 and 112, SEQ ID NOS: 113 and 114, SEQ ID NOS: 115 and 116, SEQ ID NOS: 117 and 118, SEQ ID NOS: 199 and 200, SEQ ID NOS: 201 and 202, SEQ ID NOS: 203 and 204, SEQ ID NOS: 205 and 206, SEQ ID NOS: 207 and 208, SEQ ID NOS: 209 and 210, SEQ ID NOS: 211 and 212, SEQ ID NOS: 213 and 214, SEQ ID NOS: 215 and 216, SEQ ID NOS: 217 and 218, SEQ ID NOS: 219 and 220, SEQ ID NOS: 221 and 222, SEQ ID NOS: 224 and 225, SEQ ID NOS: 227 and 228, SEQ ID NOS: 227 and 228, SEQ ID NOS: 230 and 231.
[0020]Also provided are kits that include one or more of the aforementioned pairs of primers.
BRIEF DESCRIPTION OF THE FIGURES
[0021]FIGS. 1A-1DD set forth the nucleotide sequences for SEQ ID NOS: 1-54. Sequences are presented in accordance with convention from left to right and top to bottom.
[0022]FIGS. 2A-2KK set forth the nucleotide sequences for SEQ ID NOS: 119-198. Sequences are presented in accordance with convention from left to right and top to bottom.
DETAILED DESCRIPTION OF THE INVENTION
[0023]The invention provides a method of diagnosing cancer by assaying for the methylation of one or more CpG islands that are indicative of cancer. Cancer can include, for example, lung, liver, pancreas, head and neck, throat, thyroid, esophagus, brain, ovarian, kidney, skin, colorectal, and hematopoeietic (e.g., lymphomas and leukemic) cancer. Generally, the method comprises providing a biological sample from a subject in need of cancer diagnosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD or LRRC49. In preferred embodiments, the method can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Methylation of the CpG islands associated with these genes is indicative of cancer.
[0024]The invention further provides a method of diagnosing prostate cancer by assaying for the methylation of one or more CpG islands that are indicative of prostate cancer in a male mammal. In one embodiment, the method comprises providing a biological sample from a male mammal in need of cancer diagnosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD and LRRC49. For example, the method of diagnosing prostate cancer includes assaying the biological sample for methylation of a CpG island associated with NRG1, KIF13B, or both. In another example, the method includes assaying for methylation of a CpG island associated with at least one gene selected from the group consisting of: TDH, ASAH1, FGF20, HEMK1, PALD NEUROG, EFHA2, KIFC2, GFRA1, DKK2, TNFSF11, NTN1, and RHOD. In preferred embodiments, the method of diagnosing prostate cancer can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Methylation of the CpG islands associated with these genes is indicative of cancer.
[0025]The foregoing method of diagnosing prostate cancer can optionally include, in combination with assaying for methylation of CpG islands associated with the foregoing genes, further assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be (i) methylated in prostate cancer and (ii) not detectably methylated or methylated at a lower level (e.g., about 50% or less, about 40% or less, about 30% or less, about 20% or less, or less than about 10%) in BPH. In this regard, when the method includes assaying for at least one CpG island that is known to be methylated in prostate cancer but is known not to be detectably methylated or methylated at a lower level in BPH, the method preferably includes assaying the biological sample for methylation of CpG islands associated with at least three different genes. Examples of CpG islands known to be methylated in prostate cancer but not detectably methylated or methylated at a lower level in BPH include CpG islands associated with glutathione S-transferase P1 (GSTP 1), glutathione peroxidase 3 (GPX3), glutathione S-transferase M1 (GSTM1), glutathione S-transferase M4 (GSTM4), Cub and Sushi multiple domains1 (CSMD1), tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), tumor necrosis factor receptor superfamily member 10C (TNFRSF10C), tumor necrosis factor receptor superfamily 10D (TNFRSF10D), secreted frizzled-related protein 1 (SFRP1), secreted frizzled-related protein 2 (SFRP2), dickkopf homolog 3 (DKK3), prostaglandin-endoperoxide synthase 2 (PTGS2), cyclin-dependent kinase inhibitor 1C (CDKN1C/p57), Ras association (RalGDS/AF-6) domain family 1 (RASSF1), and G-protein coupled receptor 62 (GPR62).
[0026]The invention also provides a method of prognosticating cancer by assaying for the methylation of one or more genes that are indicative of the grade or stage of the cancer, and/or the length of disease-free survival following treatment for cancer. Generally, the method comprises providing a biological sample from a subject in need of cancer prognosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD and LRRC49. In preferred embodiments, the method can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Methylation of the CpG islands associated with these genes is indicative of the grade or stage of the cancer, and/or the length of disease-free survival following treatment for cancer.
[0027]The invention also provides a method of prognosticating prostate cancer in a male mammal by assaying for the methylation of one or more CpG islands that are indicative of the grade or stage of the prostate cancer, and/or the length of disease-free survival following treatment for prostate cancer. In one embodiment, the method comprises assaying a biological sample from the male mammal for methylation of a CpG island associated with at least one of the following genes: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTRIA, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, or ISL2. In addition to or instead of the foregoing, the method can include assaying the biological sample for methylation of a CpG island associated with at least one of the following genes: KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD or LRRC49. For example, the method of diagnosing prostate cancer includes assaying the biological sample for methylation of a CpG island associated with NRG1, KIF13B, or both. In another example, the method includes assaying for at least one of the following genes: TDH, ASAH1, FGF20, HEMK1, PALD NEUROG, EFHA2, KIFC2, GFRA1, DKK2, TNFSF11, NTN1, or RHOD. In preferred embodiments, the method of diagnosing prostate can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Methylation of the CpG islands associated with these genes is indicative of the grade or stage of prostate cancer, and/or the length of disease-free survival following treatment for prostate cancer.
[0028]The foregoing method of prognosticating prostate cancer can optionally include, in combination with assaying for methylation of CpG islands associated with the foregoing genes, further assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be (i) methylated in prostate cancer and (ii) not detectably methylated or methylated at a lower level (e.g., about 50% or less, about 40% or less, about 30% or less, about 20% or less, or less than about 10%) in BPH. Percent methylation level in BPH refers to the percent of patients that exhibit some detectable level of methylation at that locus. In this regard, when the method includes assaying for methylation of at least one CpG island that is known to be methylated in prostate cancer but is known not to be detectably methylated or is methylated at a lower level in BPH, the method preferably includes assaying the biological sample for methylation of CpG islands associated with at least three different genes. Examples of CpG islands known to be methylated in prostate cancer but not detectably methylated or methylated at a lower level in BPH include CpG islands associated with GSTP1, GPX3, GSTM1, GSTM4, CSMD1, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, SFRP1, SFRP2, DKK3, PTGS2, CDKN1C/p57, RASSF1, and GPR62. Methylation of CpG islands associated with the genes is indicative of the grade or stage of the prostate cancer, and/or the length of disease-free survival following treatment for prostate cancer.
[0029]Obtaining information about the aggressiveness of the cancer, its grade, and its stage is helpful when choosing a course of treatment. The patterns of CpG methylation may be correlated to the pathological stage and grade of the tumor. For example, in prostate cancer, patterns of CpG methylation may be correlated to the Gleason score of the primary tumor. The molecular information derived from CpG methylation may also be correlated to the likelihood of survival and the length of disease-free survival following treatment. The above prognostic methods can enable the prediction of the course of the cancer, as well as the prediction of the best approach to treatment.
[0030]Also provided are methods of assessing the efficacy of treatment of cancer by assaying for the reduced methylation of CpG islands that indicates efficacy of treatment. Generally, the method comprises providing a first and a second biological sample from a subject in need of assessing the efficacy of treatment of cancer and assaying the samples for a change in methylation level of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD and LRRC49. Generally, the first biological sample is taken (e.g, prior to commencing treatment or during treatment) before the second biological sample, and the second biological sample is taken after a course of treatment. In preferred embodiments, the method includes assaying for a change in methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. A decrease or absence of methylation of the assayed one or more CpG islands in the second sample (i.e., following the course of treatment) indicates that the treatment is effective. Alternatively, the maintenance or increase of methylation in the assayed CpG islands in the second sample can indicate a reduction or absence of treatment efficacy.
[0031]The invention provides a method of assessing the efficacy of treatment of prostate cancer in a male mammal by assaying for the reduced methylation of CpG islands that indicate efficacy of treatment of prostate cancer. In one embodiment, the method comprises assaying biological samples, which are taken from the male mammal periodically during the course of treatment, for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, and ISL2. In addition to or instead of the foregoing, the method can include assaying the biological samples for methylation of a CpG island associated with at least one gene selected from the group consisting of: KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD and LRRC49. For example, the method of assessing the efficacy of treatment of prostate cancer includes assaying the biological sample for methylation of a CpG island associated with NRG1, KIF13B, or both. In another example, the method includes assaying for a CpG island associated with at least one gene selected from the group consisting of: TDH, ASAH1, FGF20, HEMK1, PALD NEUROG, EFHA2, KIFC2, GFRA1, DKK2, TNFSF11, NTN1, and RHOD. In preferred embodiments, the method can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Generally, the assayed biological samples in the method include a first and a second biological sample. The first biological sample can be taken, for example, prior to commencing treatment or during treatment, though in any event prior to taking the second biological sample. The second biological sample is taken during or after a course of treatment. A decrease or absence of methylation of the assayed one or more CpG islands in the second sample (i.e., following the course of treatment) as compared to the first sample indicates that the treatment is effective. Alternatively, the maintenance or increase of methylation in the assayed CpG islands in the second sample as compared to the first sample can indicate a reduction in or absence of treatment efficacy.
[0032]The foregoing method of assessing the efficacy of prostate cancer treatment can optionally include, in combination with assaying for methylation of CpG islands associated with the foregoing genes, further assaying the biological sample for reduced methylation of a CpG island associated with at least one gene that is known to be (i) methylated in prostate cancer and (ii) not detectably methylated or methylated at a lower level (e.g., about 50% or less, about 40% or less, about 30% or less, about 20% or less, or less than about 10%) in BPH. In this regard, when the method includes assaying the biological samples for methylation of at least one CpG island that is known to be methylated in prostate cancer but known not to be detectably methylated or methylated at a lower level in BPH, the method preferably includes assaying for methylation of CpG islands associated with at least three different genes. Examples of CpG islands known not to be methylated in prostate cancer but not detectably methylated or methylated at a lower level in BPH include GSTP1, GPX3, GSTM1, GSTM4, CSMD1, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, SFRP1, SFRP2, DKK3, PTGS2, CDKN1C/p57, RASSF1, and GPR62. A decrease or absence of methylation of the CpG islands associated with the assayed genes in the second sample as compared to the first sample following some or all of the course of treatment indicates that the treatment is effective. Alternatively, the maintenance or increase of methylation in the assayed CpG islands in the second sample as compared to the first sample can indicate a reduction or absence of treatment efficacy.
[0033]CpG islands (Bird, Nature 321: 209-213 (1986); and Gardiner-Garden et al., J. Molec. Biol. 196: 261-282 (1987)) comprise about 1% of vertebrate genomes and account for about 15% of the total number of CpG dinucleotides. CpG islands typically are between about 0.2 and about 2.0 kb in length. They can be located upstream of (e.g., in a promoter or enhancer region) of the coding sequence of the associated genes or they may also extend into or be found within gene-coding regions of their associated genes. A gene-coding region can include exons and introns. Use of the phrase "associated with" to describe a CpG island's relation to a gene, is intended to encompass CpG islands that are upstream of gene coding sequences as well as internal CpG islands. For example, the CpG island associated with the RET gene is internal and not expected to affect the expression of the RET gene when methylated. Some CpG islands are associated with the promoter of two genes and it can affect the expression of both genes. CpGs were labeled based on their location with respect to the nearest gene. In some cases, a CpG island may be located near the promoter of two different genes and may in this case influence the expression of both genes. In such case, the CpG island was named after one of the genes. For example, the LRRC49 CpG island is also associated with the THAP domain containing 10 (THAP10) gene. A CpG island can also be associated with a pseudogene or be located in a genomic region that includes no known genes or pseudogenes. The CpG island can still be of interest so long as its methylation status correlates with a disease status.
[0034]A CpG island can be separated by up to 25 kilobases (kb) (e.g., up to 20 kb, up to 19 kb, up to 18, kb, up to 17 kb, up to 16 kb, up to 15 kb, up to 10 kb, up to 9 kb, up to 8 kb, up to 7 kb, up to 6 kb, up to 5 kb, up to 4 kb, up to 3 kb, up to 2 kb, or up to 1 kb) from the transcription start site for the nearest gene and still be considered "associated with" the gene. Preferably, CpG islands associated with at least three genes are assayed. However, CpG islands associated with 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or even more genes can be assayed.
[0035]Methods of identifying CpG islands have been described (e.g., Takai et al., Proc. Nat'l. Assoc. Sci. USA, 99:3740-3745 (2002)). For example, genomic sequences can be analyzed to identify segments containing CpG islands that are at least 200 bp in length, have at least a 60% GC content, and contain at least 7% CpG dinucleotides. Preferred sequences are at least 250 bp in length, are at least 60% GC rich, and contain at least 7% CpG dinucleotides. Moreover, undesirable highly repetitive sequences can be screened out using a repeat masker that filters out sequences. Desirable sequences contain less than 50% repeats (i.e., a sequence of reduced complexity or a sequence that is present at multiple genomic locations) within the length of the identified CpG island. Preferably, the CpG island is no more than 45%, 40%, 35%, 30%, 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, or 11% repetitive. Most desirable sequences are no more than 10% repetitive. Examples of repetitive sequences are available, for example, at the web site for National Center for Biotechnology Information (NCBI).
[0036]Biological sample" is intended to encompass any suitable sample that enables accurate assay of CpG island methylation. Examples of suitable biological samples include, but are not limited to, whole blood, blood plasma, blood serum, urine, saliva, cells (e.g., cells obtained from blood, such as epithelial cells), and tissue. Such samples are obtained in accordance with methods known in the art. When the biological sample is whole blood, blood plasma, or urine, preferably, CpG islands associated with more than three genes are assayed.
[0037]A CpG island is "not detectably methylated" when it is not methylated or it is methylated at a level below the level of sensitivity of the assay method employed.
[0038]Noncancerous" tissue can be benign or normal. Alternatively, but not preferably, the tissue can be diseased, as long as it is not cancerous.
[0039]Methods of assaying methylation of CpG islands are known in the art and include, for example, restriction enzyme-based technology, such as one that employs digestion with a methylation-sensitive restriction endonuclease coupled with Southern blot analysis, methylation-sensitive enzymes and polymerase chain reaction (PCR), such as methylation-sensitive arbitrarily primed PCR (AP-PCR; see, e.g., Gonzalgo et al., Cancer Res., 57: 594-599 (1997)), restriction landmark genomic scanning (RLGS; see, e.g., Plass et al., Genomic 58: 254-262 (1999)), methylated CpG island amplification (MCA; see, e.g., Toyota et al., Cancer Res., 59: 2307-2312 (1999)), differential methylation hybridization (DMH; see, e.g., Huang et al., Human Mol. Genet., 8: 459-470 (1999)), and Not I-based differential methylation hybridization (see, e.g., International Patent Publication No. WO 02/086163). Other methods are described in U.S. Pat. App. Pub. No. 2003/0170684 and International Patent Publication No. WO 04/05122.
[0040]Alternatively, cytosine conversion-based technology can be used. Such technology relies on methylation status-dependent chemical modification of CpG islands (i.e., deamination of unmethylated cytosines in CpG islands) within isolated genomic DNA or fragments thereof followed by DNA sequence analysis. Such methods employ reagents like hydrazine and bisulfite. Bisulfite treatment followed by alkaline hydrolysis is described by Olek et al., Nucl. Acids Res., 24: 5064-5066 (1996); and Frommer et al., PNAS USA, 89: 1827-1831 (1992). The use of methylation-sensitive primers to assay methylation of CpG islands in isolated genomic DNA is described by Herman et al., PNAS USA, 93: 9821-9826 (1996), and in U.S. Pat. Nos. 5,786,146 and 6,265,171. Bisulfite-treated DNA can be subsequently analyzed by conventional molecular techniques, such as PCR amplification, fluorescence-based, real-time PCR (see, e.g., Eads et al., Cancer Res., 59: 2302-2306 (1999); Heid et al., Genome Res., 6: 986-994 (1996); and U.S. Pat. No. 6,331,393), sequencing, oligonucleotide hybridization detection, and methylation-sensitive single nucleotide primer extension (Ms-SNuPE; see, e.g., Gonzalgo et al., Nucl. Acids Res., 25: 2529-2531 (1997); and U.S. Pat. No. 6,251,594).
[0041]A preferred method of assaying for methylation of a CpG island includes isolating genomic DNA (and/or fragments thereof) from a biological sample, treating the DNA under deaminating conditions that convert unmethylated cytosines to uracil, using the treated DNA as a template in a PCR reaction to amplify a target sequence that includes the CpG-island of interest, thereby producing an amplified sequence. Unmethylated cytosines in the target sequence, which are converted to uracils by the deaminating treatment, are amplified as thymines in the corresponding position of the amplified sequence. Since the sequence of the forward and the reverse strand of the CpG island lose their complimentarity after the deamination reaction, the methylation status of the CpG island can be determined by assaying one or both of the original strands by utilizing primers capable of annealing to the strand of interest.
[0042]The deamination reaction may not proceed to completion, which results in false positives. For example, deamination of DNA sequences using bisulfite salt is sensitive to the purity of the DNA, length of incubation, and the secondary structure of the denatured templates. Quantitative PCR methods can be used to assay for the efficiency of deamination. However, quantitative PCR methods are limited to assaying the conversion status within the sites where the primers and probes anneal to the template.
[0043]Quantitative PCR methods are also limited to assaying for the methylation of cytosines within the sites where the primers and probes anneal to the template. The primers and the probe only anneal efficiently to the templates that are fully converted and contain methylation at the appropriate cytosine nucleotides. Thus, they fail to provide methylation information for CpG dinucleotides that are not assayed for. The CpG islands may also be analyzed using direct sequencing following the deamination treatment. However, due to the heterogeneity of the methylation pattern within a CpG island and the presence of homopolymeric stretches within the sequence, direct sequencing of CpG islands can yield a sequencing pattern that is too noisy and complex for the available sequencing software.
[0044]To overcome these disadvantages and to minimize the overall cost of analysis for a clinical test, we developed a method to analyze the amplified sequences by termination-coupled linear amplification. The DNA is linearly amplified using a forward or a reverse primer in the presence of dNTPs and one or two dideoxynucleotides such as dideoxycytidine or dideoxyguanine. The amplified sequence can, optionally, be analyzed using only thymine and/or cytosine terminators when assaying for a methylated CpG dinucleotide (or adenine and/or guanine terminators when analyzing the amplified strand opposite to the CpG dinucleotide of interest) to make extension reaction products that terminate at thymines and/or cytosines nucleotides (or at guanine and/or adenine when assaying the opposite strand). The amplification reaction results in the generation of fragments with multiple lengths, each length of which corresponds to the distance in bases between the primer used for amplification and the position within the target sequence of a nucleotide that is complementary to the dideoxynucleotide added to the amplification reaction. Such amplification can result in the generation of 10 to 20 fragments from an average CpG island-containing amplicon of 100 to 150 bp. The extension products can be separated by size on an acrylamide gel and compared to (a) a size standard and/or (b) by comparing the fragments to those generated when fully unmethylated (PCR generated template or clones in E. coli) or fully methylated (enzymatically methylated in vitro) template to thereby determine the presence of cytosine (or guanine on the opposite strand) or the presence of thymine (or adenine on the opposite strand) in the amplified CpG island-containing sequence. When bisulfite is used as the deaminating agent, the amplified sequence may contain large stretches of thymine or adenine which may result in additional fragments due to the DNA polymerase slippage during amplification. Such "stutter" patterns may be minimized by selectively analyzing segments of the CpG islands that have shorter homopolymeric sequences. Stutter fragments can also be identified by analyzing the control templates.
[0045]When a fluoresent label is used to tag the primers or the dideoxynucleotides used in the terminator-coupled linear amplification, the resulting fragments may be analyzed using automated sequencing machines and software designed for determining the size of DNA fragments. In this regard, commercially available software such as GENESCAN (Applied Biosystems, Foster City, Calif.) and GENEMAPPER (Applied Biosystems) are trained to recognize and account for stutter patterns due to DNA polymerase slippage during the amplification of microsatellite repeats. Such software may also be used to account for the stutter pattern that is observed when amplifying homopolymeric stretches of DNA, as might be seen after bisulfite conversion of CpG islands. There are a number of fluorescent dyes available for the automated analysis of DNA such as but not limited to 6-carboxyfluorescein (6-FAM), Hexachlorofluorescein (HEX), VIC dye, 5-carboxytetramethylrhodamine (TAMRA), 5-carboxy-X-rhodamine, succinimidyl ester (5-ROX), 6-carboxy-2',4,7,7'-tetrachlorofluorescein (TET). The methods and equipment to determine amplicon size have been available for over a decade and in use for genetic linkage mapping, DNA identity, and forensic. For example, Applied Biosystems has a set of 5 dyes that can be used to multiplex fragments from 4 separate amplification reaction and one standard for use in linkage mapping on the ABI sequencers. Four different CpG islands from a single individual can be linearly amplified using fluorescently tagged primers, and the products pooled before analysis. Alternatively, different CpG islands from different individuals can be linearly amplified using fluorescently tagged primers, and the products pooled before analysis.
[0046]Since methylation of a particular CpG dinucleotide is not always complete in a sample, i.e., the CpG sequence is heterogenous, the methods provided herein can be advantageously used to analyze the extent of or percent methylation of a particular CpG dinucleotide site within a sample. In a preferred method, two different fluorescent-dye terminators are used for thymine and cytosine, respectively (or adenine and guanine, respectively, when analyzing the opposite strand) in a fluorescent dideoxy sequencing reaction. The relative abundance of the two dyes in same-size extension products are indicative of the relative abundance of the two nucleotides at a particular sequence position, and can thereby indicate the percent methylation of a particular CpG dinucleotide site within a CpG island. To determine the expected relative abundance of the two dyes, control reactions with a range of known ratios of fully methylated to fully unmethlylated templates can be used. The data obtained from the control reactions can be used as a reference to estimate relative abundance of methylated and unmethylated cytosines in a sample.
[0047]The levels of methylation or patterns of methylation at given CpG islands can be assayed as appropriate. The assay can employ the use of a reference standard when appropriate to enable the determination of abnormal methylation. A reference standard can be determined based on reference samples obtained from age-matched noncancerous classes of adjacent tissues, and with normal peripheral blood lymphocytes. When, for example, efficacy of treatment is being assessed, the assay results of biological samples taken over the course of treatment can be compared without the use of a reference standard.
[0048]When the DNA obtained from a biological sample is in limited quantities and is not sufficient for the analysis of multiple markers, the methods described herein can include amplifying the DNA from the sample. Amplification can be done using PCR amplification or isothermal amplification methods, for example, those described in U.S. Pat. Nos. 5,854,033; 6,124,120; 6,143,495; 6,210,884; 6,642,034; 6,280,949; 6,632,609; and 6,642,034; and U.S. Pat. App. Pub. Nos. 2003/0032024; 2003/0143536; 2003/0235849; 2004/0063144; and 2004/0265897, which are incorporated herein by reference in their entirety. Isothermal amplification can include rolling circle or strand displacement amplification. Methods that combine PCR and isothermal amplification have also been described (U.S. Pat. Nos. 6,777,187; and 6,828,098; and U.S. Pat. App. Pub. Nos. 2004/0209298; 2005/0032104; and 2006/0068394, each of which is incorporated herein by reference in its entirety). U.S. Pat. App. Pub. No. 2005/0202490, which is incorporated herein by reference in its entirety, describes the use of such methods in combination with methylation-sensitive restriction enzymes to study the methylation pattern of DNA. DNA amplification can also include methylation-coupled whole genomic amplification to generate the DNA needed, such as described in U.S. Pat. App. Pub. No. 2006/0257905, which is incorporated by reference herein in its entirety. The methylation-coupled whole genomic amplification can be especially advantageous when DNA is recovered from minute biological samples or from bodily fluids such as urine or plasma.
[0049]Skilled artisans will appreciate that the various amplification methods described herein, e.g., the PCR amplification, isothermal amplification, and termination-coupled linear amplification method, can employ nucleotides, nucleotide analogues, nucleotide or nucleotide analogue derivatives, and/or combinations thereof.
[0050]If desired, mRNA and protein levels can be assayed, and alterations in their expression levels can be indicative of a change in the level of methylation or the patterns of methylation at given CpG islands. Such methods of assaying mRNA and protein levels are also within the skill in the art. For example, the mRNA assay methods described in U.S. Provisional Patent Application No. 60/705,964 filed on Aug. 5, 2005 and International Patent Publication No. WO 2007/019444, which are hereby incorporated by reference, can be used. Such methods are particularly useful if a degraded tissue sample is used as the biological sample. Alternatively, reverse transcription with gene-specific primers can be used to assay mRNA levels. Proteins levels can be assayed, for example, using antibody and staining techniques.
[0051]It is important to note that even though aberrant methylation of a CpG island can affect expression of the associated gene, the methods described herein are not dependent on a biological role for the hypermethylation. That is a hypermethylated CpG island can be useful in the methods of the invention regardless of its effect on gene expression. Accordingly, the only requirement is that there be a correlation between the methylated state of a CpG island and the presence of cancer.
[0052]The invention further provides target sequences and corresponding primers or probes that are useful in the above methods. The target sequences provide the context for the selection of CpG islands to assay for methylation. If a given target sequence contains more than one CpG island, all or less than all of the CpG islands, even one CpG dinucleotide, can be assayed for methylation with respect to that particular target sequence. In this regard, a target sequence can include a genomic sequence that is fully methylated and fully deaminated such as SEQ ID NO: 1 or 2 [NRG1], SEQ ID NO: 3 or 4 [ADRB3], SEQ ID NO: 5 or 6 [GFRA2], SEQ ID NO: 7 or 8 [KIF13B], SEQ ID NO: 9 or 10 [RET], SEQ ID NO: 11 or 12 [GPR147], SEQ ID NO: 13 or 14 [NEUROG3], SEQ ID NO: 15 or 16 [PALD], SEQ ID NO: 17 or 18 [HEMK1], SEQ ID NO: 19 or 20 [FGF4], SEQ ID NO: 23 or 24 [HTR1A], SEQ ID NO: 25 or 26 [RNF180], SEQ ID NO: 27 or 28 [ECOP], SEQ ID NO: 29 or 30 [ZNF596], SEQ ID NO: 33 or 34 [LOC441320], SEQ ID NO: 35 or 36 [TDH], SEQ ID NO: 37 or 38 [FLJ36980], SEQ ID NO: 39 or 40 [FGF20], SEQ ID NO: 41 or 42 [EFHA2], SEQ ID NO: 43 or 44 [ASAH1], SEQ ID NO: 45 or 46 SEQ ID NO: 49 or 50 [NODAL], SEQ ID NO: 51 or 52 [LOC399783], SEQ ID NO: 53 or 54 [ISL2]. These fully methylated and deaminated sequences are used for illustrative purposed and do not exclude the use of partially methylated and deaminated sequences in the methods of the invention. A target sequence can include a genomic sequence that is partially methylated, such as in DNA obtained from a tumor, and then deaminated such that the target differs from the sequence listed above. Persons of skill in the art will appreciate that a target sequence that includes a partially methylated and deaminated CpG island will result in a population of DNA molecules that differ at one or more positions that correspond to the cytosine residues in one or more CpG dinucleotides. Thus, a target sequence can include a variety of partially methylated and deaminated sequences based on the following genomic sequences SEQ ID NOS: 119 or 220 [KIFC2], SEQ ID NOS: 121 or 122 [C20ORF23], SEQ ID NOS: 123 or 124 [GFRA1], SEQ ID NOS: 129 or 130 [DKK2], SEQ ID NOS: 133 or 134 [RASSF5], SEQ ID NOS: 135 or 136 [NTN1], SEQ ID NOS: 139 or 140 [GPR147], SEQ ID NOS: 141 or 142 [NEUROG3], SEQ ID NOS: 143 or 144 [NODAL], SEQ ID NOS: 145 or 146 [PALD], SEQ ID NOS: 147 or 148 [LOC399783], SEQ ID NOS: 151 or 152 [LOC441320], SEQ ID NOS: 153 or 154 [ZNF596], SEQ ID NOS: 155 or 156 [TDH], SEQ ID NOS: 157 or 158 [ASAH1], SEQ ID NOS: 159 or 160 [FGF20], SEQ ID NOS: 161 or 162 [FLJ36980], SEQ ID NOS: 163 or 164 [GFRA2], SEQ ID NOS: 165 or 166 [EFHA2], SEQ ID NOS: 171 or 172 [KIF13B], SEQ ID NOS: 173 or 174 [ADRB3], SEQ ID NOS: 175 or 176 [NRG1], SEQ ID NOS: 177 or 178 [ECOP], SEQ ID NOS: 179 or 180 [HTR1A], SEQ ID NOS: 181 or 182 [ISL2], SEQ ID NOS: 183 or 184 [LOC285671], SEQ ID NOS: 185 or 186 [FGF4], SEQ ID NOS: 189 or 190, [HEMK1], SEQ ID NOS: 191 or 192 [RET] SEQ ID NOS: 193 or 194 [HTRA4], SEQ ID NO: 195 [RHOD], SEQ ID NO: 196[TNFSF11], SEQ ID NO: 197 [MMP9], and SEQ ID NO: 198 [LRRC49].
[0053]These targets can be used in combination with known targets (for example known CpG islands associated with GSTP1, GPX3, GSTM1, GSTM4, CSMD1, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, SFRP1, SFRP2, DKK3, PTGS2, CDKN1C/p57, RASSF1, and GPR62. For example, fully methylated and deaminated sequences for some of these genes are provided in SEQ ID NO: 31 or 32 [CSMD1], SEQ ID NO: 45 or 46 [TNFRSF10C], SEQ ID NO: 47 or 48 [TNFRSF10B] SEQ ID NO: 21 and 22 [GPR62]. Also for example, a target sequence can include fully or partially methylated and (subsequently) deaminated sequences based on the following genomic sequences SEQ ID NOS: 131 or 132 [GPX3], SEQ ID NOS: 125 or 126 [GPX7], SEQ ID NOS: 127 or 128 [GSTM4], SEQ ID NOS: 137 or 138 [SFRP2], SEQ ID NOS: 149 or 150 [CSMD1], SEQ ID NOS: 167 or 168 [TNFRSF10B], SEQ ID NOS: 169 or 170 [TNFRSF10C], and SEQ ID NOS: 187 or 188 [GPR62]. Such target sequences can be isolated or purified in accordance with methods known in the art.
[0054]Also provided are isolated or purified primers derived from and suitable for amplifying sequences internal to the above isolated or purified nucleic acid molecules. The isolated or purified primers can be DNA, RNA, PNA, and the like. It will be understood by one of ordinary skill in the art, however, that one type of nucleic acid can be preferred over another, depending on the particular biological sample, the methodology employed in assaying CpG islands for methylation, and the ability of the particular type of nucleic acid to detect methylation. One or more (e.g., two, three four, four, five, six, seven, eight, nine ten or more) isolated pairs of primers can be provided. Optionally, primers are provided as part of a kit useful in the methods disclosed herein. The pair of primers can consist essentially of SEQ ID NOS: 55 and 56, SEQ ID NOS: 57 and 58, SEQ ID NOS: 59 and 60, SEQ ID NOS: 61 AND 62, SEQ ID NOS: 63 and 64, SEQ ID NOS: 65 and 66, SEQ ID NOS: 67 and 68, SEQ ID NOS: 69 and 70, SEQ ID NOS: 71 and 72, SEQ ID NOS: 73 and 74, SEQ ID NOS: 75 and 76, SEQ ID NOS: 77 and 78, SEQ ID NOS: 79 and 80, SEQ ID NOS: 81 and 82, SEQ ID NOS: 83 and 84, SEQ ID NOS: 85 and 86, SEQ ID NOS: 87 and 88, SEQ ID NOS: 89 and 90, SEQ ID NOS: 91 and 92, SEQ ID NOS: 93 and 94, SEQ ID NOS: 95 and 96, SEQ ID NOS: 97 and 98, SEQ ID NOS: 99 and 100, SEQ ID NOS: 101 and 102, SEQ ID NOS: 103 and 104, SEQ ID NOS: 105 and 106, or SEQ ID NOS: 107 and 108. It is understood that these primer pairs are examples of suitable primers for use in the context of the invention. For example, each primer can be between 10 and 40 nucleotides and together the pair of primers can flank a region of at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 130, 140, 150, 200, 250, 300 bp in length that includes one or more CpG dinucloetides in a CpG island of interest. Primer pairs can be modified in various ways, such as by chemical modification of a base, and still be useful in the context of the invention. Other primers derived from the target sequences, namely SEQ ID NOS: 1-54 and 119-198, and variants thereof, also can be used in the context of the invention. The only requirement is that such primers function to assay for methylation of a given CpG island. Thus, for example, alternate primers can be selected or the provided primers can be modified or provided in degenerate form to account for target sequence polymorphisms within a given population, so long as the primers are still suitable for assaying modification of CpG islands associated with the genes disclosed herein.
[0055]Like the target sequences, the primer pairs can be isolated or purified in accordance with methods known in the art. Alternatively, they can be synthesized using routine methods.
[0056]The primers can be part of a kit. Preferably, the kit comprises at least three pairs of primers, wherein each primer pair is specific for a CpG island associated with a different gene. However, the kit can comprise additional primer pairs, such as primer pairs for other CpG islands associated with the same gene or primer pairs for amplifying CpG islands associated with four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or even more genes. The kit can further comprise one or more reagents for assaying for methylation of CpG islands, instructions for use, and/or other components as are typically found in kits. For example, the kit can comprise a buffer suitable for (a) isolating genomic DNA comprising a target sequence from a biological sample, (b) amplifying a portion of the target sequence, and/or (c) deaminating a target sequence. In embodiments directed to the evaluation of prostate cancer, a kit can comprise one or more buffers suitable for preparing genomic DNA from serum and/or urine samples.
EXAMPLES
[0057]The following examples serve to illustrate the invention. The examples are not intended to limit the scope of the invention.
Example 1
[0058]This example demonstrates the determination of the methylation status of markers based on methylation-specific PCR amplification. Paraffin-embedded prostate tissues were obtained following radical prostatectomies. The tissue samples were sectioned into 23 10-micron sections and slide 1, 12, and 23 were stained using hematoxylin and eosin (H&E). Using the H&E slides as guide, the areas corresponding to the tumor tissues were microdissected from the unstained slides. The remaining tissues were recovered to use as a normal paired sample. Following deparaffinization using two xylene extractions and two ethanol washes, the DNA was isolated from the tumor tissue and surrounding normal tissues using standard proteinase K digest for 5 days at 50° C., extraction with phenol/chloroform and ethanol precipitation (Current Protocols in Molecular Biology, edited by Ausubel, et al., Wiley-Interscience (New York 1988, revised 1988-2006)). The DNA was resuspended in TE8 and the quality and quantity of the DNA was assessed by agarose gel electrophoresis using concentration and size standards as reference. Following denaturation in the presence of 0.3 M NaOH, the DNA was treated with 2.5 M sodium metabisulfite, pH 5.5, in the presence of 1 mM hydroquinone at a concentration of 1 μg of DNA/500 μl. The reaction was incubated in a thermocycler for a total of 8 cycles (95° C. for 5 minutes; 55° C. for 115 minutes).
[0059]Following bisulfite treatment, the DNA was purified using the QIAEX II purification kit (Qiagen, Valencia, Calif.) according to the manufacturer's recommendations and eluted in 50 μl of TE8. Sodium hydroxide (5.5 μl of 2 N) was added, and the DNA was incubated at RT for 15 min. The DNA was then precipitated with 3 volumes of ethanol and 0.3 volumes of 5 M NH4OAC. The DNA was resuspended in 50 μl of TE8 and stored at -20° C.
[0060]In order to determine if a specific CpG position is methylated in genomic DNA isolated from tumor tissue, methylation-specific polymerase chain reaction (PCR) was performed, using primers designed to overlap the position of the CpG island of interest. All PCR reactions were performed in a MASTERCYCLER thermocycler (Eppendorf, Westbury, N.Y.) for 42 cycles of 95° C. for 15 seconds, 63° C. for 30 seconds, and 72° C. for 10 seconds. Each reaction was carried out in 30 μl of 1× PLATINUM Taq PCR buffer containing 1.5 mM magnesium chloride, 0.25 mM dNTPS, 12.5 pmoles of each primer, and 0.5 units of PLATINUM Taq enzyme (Invitrogen, Carlsbad Calif.). The primers used for each CpG island and the size of the product are shown in Table 1, wherein "F" indicates forward primer, "R" indicates reverse primer, "m" indicates methylated, and "u" indicates unmethylated.
TABLE-US-00001 TABLE 1 An- neal- ing Gene as- temp- Pro- sociated era- duct with CpG ture size island Primer sequences (° C.) (bp) NIRG1 mF: GAGCGGGTAGCGAGAGTTTCGG 63 119 [SEQ ID NO: 55] mR: TAACGACGCGACTACCGAAAACC [SEQ ID NO: 56] ADRB3 mF: GATTAACGTGTTCGTGATTTCGTT 63 102 [SEQ ID NO: 57] mR: CAACGACCAATAACCAATCAACGCC [SEQ ID NO: 58] GFRA2 mF: ATACGTCGGTGAGTTCGGTTTATC 63 101 [SEQ ID NO: 59] mR: ACTCCCGACTCCCTAAACTCCGAA [SEQ ID NO: 60] KIF13b mF: TGAATCGGCGAGGTGAGAGTCG 65 179 [SEQ ID NO: 61] mR: ACCGAACGTCTCAACGCGAAAACG [SEQ ID NO: 62] RET mF: TATCGTTAGCGTCGTGGTGGAGTT 63 120 [SEQ ID NO: 63] mR: CTACACGAACACTAAACCGACCGA [SEQ ID NO: 64] GPR147 mF: TCGGTCGTTACGTTGATCGTTATTC 63 119 [SEQ ID NO: 65] mR: ACCCTACGCATACCCTTCTCGAAC [SEQ ID NO: 66] NEUROG3 mF: GTTTCGAGGAAGTTTCGGGTACGG 63 103 [SEQ ID NO: 67] mR: GATCGTTAACCTTCTTTCGCCGAC [SEQ ID NO: 68] PALD mF: CGAAGTTGGGAGGAGCGAGTT 63 115 [SEQ ID NO: 69] mR: AAACATCCGTACTCCTACGACCGA [SEQ ID NO: 70] HEMK [tiF: 63 99 CGTATTAGTCGTATTCGCGAGCGT [SEQ ID NO: 71] mR: CGAAACTACTCGACCCGACCC [SEQ ID NO: 72] FGF4 mF: TAACGGTACGTTGGAGGTCGAGTT 63 102 [SEQ ID NO: 73] mR: ACGACCGCCTCCTTAAACTACGCT [SEQ ID NO: 74] GPR62 mR: TATCGTGTATTCGTTGCGGTTAGG 63 120 [SEQ ID NO: 75] mR: AACGATACGAACGACGTACCGAA [SEQ ID NO: 76] HTR1A mF: TACGTGAATAAGAGGACGTTTCGG 63 115 [SEQ ID NO: 77] mR: AACGATCTTCCGAAATACGCCAA [SEQ ID NO: 78] RNF180 mF: TCGTCGAATCGGTATCGTCGTC 63 118 [SEQ ID NO: 79] mR: ACCTATATCCACGTCCCGAAACCT [SEQ ID NO: 80] ECOP mF: CGGTTGTAGTTTGTTCGTTCGTTTC 63 108 [SEQ ID NO: 81] mR: CTAACGCCTCATAACTCCTCGCGT [SEQ ID NO: 82] ZNF596 mF: GCGTCGATTCGGGAGTAGTATCGT 63 96 [SEQ ID NO: 83] mR: ATACCGTAAATCCGCGCTACTTCC [SEQ ID NO: 84] CSMD1 mF: CGTTGAGGTCGAATGAAGCGTAGT 63 96 [SEQ ID NO: 85] mR: AACCGAAACTAAACACGACGCAA [SEQ ID NO: 86] LOC441320 mF: AAGCGTATAGTTCGAGGATTGCGA 63 107 [SEQ ID NO: 87] mR: CCGCGTCACTTACTCCTCTACGA [SEQ ID NO: 88] TDH mF: CGTTGGGTGCGTAGGAAGGTTAGT 63 120 [SEQ ID NO: 89] mR: GACCGACCCTAAACAACCCGCT [SEQ ID NO: 90] FLJ36980 mF: GTTGCGGGATAGCGTTGTGATT 63 96 [SEQ ID NO: 91] mR: ACCATTATCAATACTCCGATCGCC [SEQ ID NO: 92] FGF20 mF: TTTGTTTGTTAAGGGCGTTATCGT 63 105 [SEQ ID NO: 93] mR: CCGCGACTACTCTAACCAACCC [SEQ ID NO: 94] EFHA2 mF: GGGCGTTGAGTTTAGTTCGGAGA 63 108 [SEQ ID NO: 95] mR: ACGAACACAACCGAATCAACGTAA [SEQ ID NO: 96] ASHA1 mF: GGCGTTGGTTGTTAGAGCGATG 63 114 [SEQ ID NO: 97] mR: GACTCAAACTCACTCACCGACGAC [SEQ ID NO: 98] TNFRSF10C mF: GGTGCGATTTAGGATTTAGGACGG 63 115 [SEQ ID NO: 99] mR: GCGACCGAAACTCACTAACAACAA [SEQ ID NO: 100] TNFRSF10B mF: GCGATTTGGGTCGTTAGGGAATAG 63 119 [SEQ ID NO: 101] mR: ACCTCTCCGTAACTTCACGCAACTT [SEQ ID NO: 102] NODAL mF: GGTAGTCGCGGTCGTTTACGTT 63 111 [SEQ ID NO: 103] mR: ACGAACAAACGACAAATCGAATCA [SEQ ID NO: 104] LOC399783 mF: TACGTTGAGTTCGGTTTGGTTTGT 63 103 [SEQ ID NO: 105] mR: CGCGCCTCCGTAATCTAAACTAA [SEQ ID NO: 106] ISL2 mF: GTGCGTGTTGACGTTATGTTGCGT 63 99 [SEQ ID NO: 107] mR: CGCCCGACCTCGACTCTTTACT [SEQ ID NO: 108] GSTP1 mF: CGGCGATTTCGGGGATTTTAGGGC 63 109 [SEQ ID NO: 109] mR: GACCGCTCTTCTAAAAAATCCCGC G [SEQ ID NO: 110] GSTP1 mF: ACGTTCGGGGTGTAGCGGTCGTC 63 93 [SEQ ID NO: 111] mR: CCCCAATACTAAATCACGACGCCG [SEQ ID NO: 112] GSTP1 mF: GGTCGGCGTCGTGATTTAGTATTGG 63 99 [SEQ ID NO: 113] mR: ACTACGACGACGAAACTCCAACGA [SEQ ID NO: 114] GSTP1 uF: 63 113 TGTGGTGATTTTGGGGATTTTAGGGT [SEQ ID NO: 115] uR: CCAACCACTCTTCTAAAAAATCCCACA [SEQ ID NO: 116] GSTP1 uF: GATGTTTGGGGTGTAGTGGTTGTTG 63 99 [SEQ ID NO: 117] uR: CTCCACCCCAATACTAAATCACAACA [SEQ ID NO: 118] KIFC2 mF: TGATGGTCGTATTGCGGGTTTATC 62 91 [SEQ ID NO: 199] mR: ATACCTAAACCCAACGCCGACTAC [SEQ ID NO: 200] C20orf23 mF: CGCGATTTGAGTAGTTAGCGTCGT 62 90 [SEQ ID NO: 201] mR: AACCAACGCGACGACCTAACTAAC [SEQ ID NO: 202] GFRA1 mF: TAGATTTCGGTGTTTCGGGCGTT 62 98 [SEQ ID NO: 203] mR: CCGCTAATTCCCAATCGTACTACTCA [SEQ ID NO: 204] GPX7 mF: TTCGTTTCGTTCGGTCGTGATT 62 116 [SEQ ID NO: 205] mR: GACTACGAACGCTTCGAATTCCTC [SEQ ID NO: 206] DKK2 mF: GTTGCGTTGGTAGCGATTCGTTGT 62 117 [SEQ ID NO: 207] mR: CCCGAACCGAATCCTCGAAATCT [SEQ ID NO: 208] NTN1 mF: 62 103 GACGTAGTATGATGCGCGTAGTGTG [SEQ ID NO: 209] mR: GCGAACATACTAAACCCGAACCC [SEQ ID NO: 210] HTRA4 mF: GGATTACGTCGGTGTTCGATTTGT 62 95 [SEQ ID NO: 211] mR: AACGCACGATTAACCCTACGCC [SEQ ID NO: 212] MMP9 mF: TCGGATTAAGGTAGGCGTGGTTTC 62 102 [SEQ ID NO: 213] mR: AACGTAAACGCCGAACCGAAC [SEQ ID NO: 214] RHOD mF: GGAAGACGTCGTTGTTGATGGTTT 62 120 [SEQ ID NO: 215] mR: ACCGCTCCGACACGAACCTATAC [SEQ ID NO: 216] TNSF11 mF: AGCGTTATGCGTCGCGTTAGTAG 62 116 [SEQ ID NO: 217] mR: GCAAACGACGACGAAACGTACA [SEQ ID NO: 218] SFRP2 mF: GAAGAGAGCGGGTTCGGGATAAG 62 101 [SEQ ID NO: 219] mR: CTACAACATCGTAAACGCGCGAC [SEQ ID NO: 220]
[0061]The products of the PCR reactions were separated on 8% acrylamide gel. Only templates that exhibited methylation at all of the CpG islands that were present within the primers could serve as efficient templates for the amplification reactions. Control reactions were performed using fully methylated templates that were methylated in vitro using SS1 (CpG) methylase (NEB, Beverly, Mass.) according to the manufacturer's protocol. All primer pairs listed in Table 1 yielded a product of the correct size from fully methylated control template. Two negative controls (water and DNA isolated from white blood cells) were included for each target PCR amplification, which did not yield a PCR product. When a CpG island is methylated in a DNA sample, an amplification product of the expected size is obtained. This example demonstrates that the above primers can be used to assay for methylation of CpG islands in prostate cancer and that the CpG islands exhibit methylation in prostate cancer.
Example 2
[0062]This example demonstrates the determination of the methylation status of CpG islands at the ADRB3 locus by DNA sequencing. DNA is obtained from tumor samples and treated with sodium bisulfite as described in example 1. Two microliters of the bisulfite treated DNA are amplified with the following primers: ADRB3-F1: GAGAAGAGGAAGGTAGAAGGAG [SEQ ID NO: 221] and ADRB3-R1: CTACCTAACTATAACCAACCC [SEQ ID NO: 222] for 40 cycles as described in example 1 except for the annealing temperature, which is lowered to 55° C. The amplified 250 bp product is purified using QIAquick PCR purification kit (Qiagen, Valencia Calif.) and recovered in TE8. Fifty nanograms of the ADRB3 amplified product is sequenced using 1.25 pmole of ADRB3-F2:ACGGAGGAGGATAGTAGTACG [SEQ ID NO: 223] using BigDye Terminator v3.1 cycle sequencing kit (Applied Biosystems) and the sequencing reaction is purified using Centri-Sep columns (Applied Biosystems) according to the manufacturer's protocols. The products of the sequencing reaction are analyzed using an ABI 3700 sequencer according to manufacturer's specification. The resulting DNA sequence shows one or more sequence peaks corresponding to cytosine base or a mixed cytosine/thymidine base at the cytosine residue position of CpG dinucleotides that are fully or partially methylated in the original tumor DNA.
[0063]Alternatively, a more detailed sequence analysis is obtained by cloning the product of the amplification reaction using a TOPO TA cloning kit (Invitrogen, Carlsbad Calif.) according to supplier's protocol. Approximately 20 colonies are chosen for further analysis. Each colony is grown in 3 ml of LB media for 16 hours. DNA is isolated from 1.5 ml aliquot using plasmid preparation kit from Qiagen. The plasmid DNA is quantitated using spectrophotometer and 1 microgram aliquot is sequenced as described above. The sequence of the 20 individual clones is compared to determine which cytosines are methylated and to provide an estimate of their rate of methylation in the tumor sample. This example shows that the methylation status of cytosines within CpG islands can be determined using a sequencing approach.
Example 3
[0064]This example demonstrates the determination of the methylation pattern of multiple CpG islands associated with KIFC2, GFRA1 and GPX7 using terminator-coupled linear amplification. From DNA from tumor samples prepared as described in example 1, fragments of the CpG islands associated with KIFC2, GFRA1, GPX7 are amplified individually using the mF1 and mR1 primers shown below for each CpG island. The amplification reactions are performed for 42 cycles as described in example 1 except for the annealing temperature, which was lowered to 58° C. An aliquot of the amplification reaction is separated on an 8% acrylamide gel to verify that fragments of the appropriate length are obtained (264 bp for KIFC2, 326 bp for GFRA1, 367 bp for GPX7). The product of the PCR reaction were purified using QIAQUICK PCR purification kit (Qiagen).
[0065]Each amplification product (25 nanograms) is subjected to linear terminator-coupled amplification using 1.5 pmoles of the fluorescently labeled F2 primer shown below for the corresponding amplicon. The amplification reaction includes 1× VentR (exo-) DNA polymerase (New England Biolabs, Beverly Mass.), 30 μM dATP, 37 μM dCTP, 100 μM dGTP, 100 M dTTP, 480 μM ddCTP and 2 units of VentR (exo-) DNA polymerase. Reactions are performed in an MASTERCYCLER thermocycler (Eppendorf) for 30 cycles of 95° C. for 15 seconds, 58° C. for 30 seconds, and 72° C. for 30 seconds. Following amplification, the reaction products are pooled into a single tube and purified using Centri-Sep columns (Applied Biosystems) according to the manufacturer's protocols. One microliter of GENESCAN 500 LIZ standard (Applied Biosystems) is added to one tenth of the purified fragment and the DNA separated using the ABI Prism 3100 Genetic Analyzer (Applied Biosystems) according to manufacture's instructions. The data is analyzed using the GENESCAN and the GENEMAPPER software (Applied Biosystems).
[0066]The following primers are used for the amplifications:
TABLE-US-00002 KIFC2-F1: AGGTA(C/T)GTTGTATTTGGTGGATTTGG [SEQ ID NO: 224] KIFC2-R1: CCCACCTACAACAACAACACC [SEQ ID NO: 225] KIFC2-F2: 6FAM-GAACGCGTACGGAAGGTAGG [SEQ ID NO: 226] GFRA1-F1: GTGATAGGTTTGTAGATTTGATAGTTG [SEQ ID NO: 227] GFRA1-R1: AACTAACCTCCATTTTAACTATTTC [SEQ ID NO: 228] GFRA1-F2: NED-GAGAGATGAATTTGGATATTAGT [SEQ ID NO: 229] GPX7-F1: GGTAAATTGGTGT(C/T)GTTGGAGAAG [SEQ ID NO: 230] GPX7-R1: ACTAAACAATAATACCC(A/G)ACCTC [SEQ ID NO: 231] GPX7-F2: VIC-GTCGTTGGGTTCGGTTTCGTTTTG [SEQ ID NO: 232]
[0067]The F1 and R1 primers are used for the amplification of a fragment of a CpG island from the tumor DNA. The F2 primers are used for termination-coupled linear amplification.
[0068]This example shows that termination-coupled linear amplification fragment lengths can be analyzed to (i) determine the presence and/or the positions of methylated cytosines in CpG islands in a sequence of interest as well as (ii) provide information about the efficiency of the deamination reaction, since incomplete deamination results in fragments with length that differ than what is expected from the positions of the CpG dinucleotides within the sequence.
Example 4
[0069]This example demonstrates the use of methylation-coupled whole genome amplification on DNA recovered from urine samples to increase the amount of DNA available for CpG island marker assays. Urine samples were obtained from 4 patients that were recently diagnosed with prostate cancer. 50 ml samples were spun down at 4000 rpm for 15 min, transferred to 1.5 ml tubes and washed twice with PBS. The DNA was extracted using proteinase K digest (100 μl of 25 mM Tris pH8.0, 100 mM NaCL, 1% SDS, 5 mM EDTA and 10 μg of Proteinase K followed by phenol/chloroform extraction and ethanol precipitation. The DNA was resuspended in 10 μl TE8 buffer (10 mM Tris, pH 8.0, 1 mM EDTA).
[0070]A partially random primer with the sequence GGGN6 (50 ng) was added to 5 μl of DNA. 12 μl of a denaturing solution (50 mM KOH, 0.1 mM EDTA) was added to the DNA/random primer mix. After a five-minute incubation at room temperature, 12 μl of a neutralization solution (60 mM Tris (pH 7.5), 50 mM HCl) was added to neutralize the reaction. The DNA/primer mix was denatured at 94° C. for 5 minutes, incubated at room temperature for 10 minutes, and then placed on ice.
[0071]The amplification reaction was set up in a final volume of 30 μl. The following reagents were added to give the indicated final concentrations: (a) 1×NEB buffer 2 (1×NEB buffer 2: 50 mM NaCl, 10 mM Tris-HCl, pH 7.9, 10 mM MgCl2, 1 mM dithiothreitol), 333 μM dATP, dCTP, dGTP, dTTP, 160 μM S-adenosylmethionine, and 10 ng/μl of bovine serum albumin (BSA) were combined and to which was added (b) DNA methyltransferase enzyme 1 (0.15 units/μl) (New England Biolabs) and incubated at 37° C. for 10 minutes, and followed by (c) adding Klenow polymerase to a final concentration of 0.167 units/μl, and Klenow exo- to a final concentration of 0.167 units/μl (New England Biolabs).
[0072]The reaction was incubated at 37° C. for 16 hours, and the reaction was stopped by the addition of EDTA to a final concentration of 5 mM, phenol/chloroform extracted, and ethanol precipitated. The DNA was resuspended in 40 μl of TE8 and 2 μl were separated on agarose gel to verify the presence of DNA.
[0073]The DNA was treated with sodium bisulfite and analyzed by methylation specific PCR as described in Example 1 using the GPR147 and RET assays. The presence of a band of the expected size for either marker indicated the methylation of the associated marker in the input DNA.
[0074]All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.
[0075]The use of the terms "a," "an," "the," and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.
[0076]Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. It should be understood that the illustrated embodiments are exemplary only, and should not be taken as limiting the scope of the invention.
Sequence CWU
1
23211600DNAHomo sapiens 1gagtttattt tcgtttgcgt gcgatagggt ttttgtattt
aagtgagtta aggaatgaat 60ttcgaatttt tttgggaaag ttattaacgt ttttttcgta
ttttttttag ggtttttgat 120tacggagatt ttgtttgggg tataggtgtg ggagtcgtaa
attttttttt gcgtcgtttt 180ttttcgcgtg gaatgggacg gagtagtttt tttaggcgtt
gtttggttgc ggaggggagc 240gggtagcgag agtttcgggt tttcgtttgg gttttcgggt
tttcggggcg ttggtttcgg 300ttttcgcgta gcgtttagcg atttttgtcg ggggttttcg
gtagtcgcgt cgttattttt 360cgttcggtta gcgcgggagg aaaaggggtt gcgttcggga
gcgtcgagtt taggtttttt 420tcggtggcgt gttcgcgttt cggggtgggg gtgtggtggg
gaagagggag ggggcgaggt 480taggggaggg tgcgaaggag gcgtttgttt ttaatttgcg
ggcgggaggt gggtggttgc 540ggggtaattg aaaaagagtc ggcgaggagt ttttcgaaat
ttgttggaat ttcgggttcg 600cgcggaggtt aggagttgag cggcggcggt tgtcggacga
tgggagcgtg agtaggacgg 660tgataatttt ttttcgatcg ggttgcgagg gcgtcgggta
gaggttagga cgcgagtcgt 720tagcggtggg atttatcgac gatttttcgg ggcgatagga
gtagtttcga gagttagggc 780gagcgttcgt tttaggtggt cggatcgttc gtcgcgttcg
cgtcgcgttt tttgtaggta 840acgggagacg ttttcgcgta gcgcgagcgt tttagcgcgg
tcgttcgttt tttttttcga 900gggataaatt ttttttaaat tcgattcgag tttttggatt
aaattcgttt gcgtcgagag 960tcgttcgcgt agagcgtttc gttttcggcg agatgttcga
gcgtaaagaa ggtagaggta 1020aagggaaggg taagaagaag gagcgaggtt tcggtaagaa
gtcggagttc gcggcgggta 1080gttagagttt aggtgggtgc gtagcgcggt tcgggtttta
cgattttttt tttgtttttt 1140ttattttttt tttttttcgg atgtcgtggt tttttttttt
tttttttttt cgttcgtttt 1200tttcgttttg cgttttgagc gttcgttgag tcgcgcggtg
tttttttttt tgggggtcgt 1260cgtttatttg ggcgtcgagt tttatcgggc gtttacgttt
agagtttagg gtaagggata 1320gtagtttcgg tcgtattttt ttagagtttc gggagcgttt
cgttttttgg tacggttttt 1380ttttagcgtt ttagcggttg agtttagttc gggagtggga
tttgggttat aggagtcgag 1440gttgcgtgcg cgcgtgtttc gcgttataag cgttttgtac
gggggtcgtg tgttttttag 1500cgggaaacgt tggaatgggt cgtttggagg gagagtcggt
tttttcggtg tgtttggtag 1560cgtagaagtg ggtggtcgag taagaggtcg cgtgggaagt
160021600DNAHomo sapiens 2attttttacg cggttttttg
ttcgattatt tatttttgcg ttgttaggta tatcgagggg 60atcggttttt tttttaggcg
gtttatttta gcgtttttcg ttagagggta tacggttttc 120gtgtaaagcg tttatggcgc
ggggtacgcg cgtacgtagt ttcgattttt atagtttagg 180ttttattttc gggttgggtt
tagtcgttaa ggcgttgggg aggggtcgtg ttagggagcg 240aagcgttttc gggattttgg
gagggtgcgg tcgggattgt tgttttttgt tttgagtttt 300gggcgtaggc gttcggtagg
attcggcgtt taggtgagcg gcggttttta ggaggggaag 360tatcgcgcga tttaacgggc
gtttagagcg tagggcgaag aggacgggcg agggagaggg 420ggagggagag gttacggtat
tcgaggagga ggaggagtag gaggagtagg aggaggatcg 480tggggttcgg gtcgcgttgc
gtatttattt gggttttggt tgttcgtcgc ggatttcggt 540tttttgtcgg agtttcgttt
tttttttttg tttttttttt tgtttttgtt ttttttgcgt 600tcggatattt cgtcggagac
ggagcgtttt acgcggacgg ttttcggcgt aggcgagttt 660ggtttaaggg ttcggatcgg
gtttgggaaa agtttgtttt tcgaggggga gagcgagcgg 720tcgcgttgag gcgttcgcgt
tgcgcggggg cgtttttcgt tgtttgtagg gagcgcggcg 780cggacgcggc gggcggttcg
gttatttgga acgggcgttc gttttggttt tcggggttgt 840ttttgtcgtt tcgggaagtc
gtcgatgggt tttatcgttg gcggttcgcg ttttggtttt 900tgttcggcgt tttcgtaatt
cgatcgggga gaggttatta tcgttttgtt tacgttttta 960tcgttcggta gtcgtcgtcg
tttagttttt ggttttcgcg cgagttcgga gttttaataa 1020gtttcgggga atttttcgtc
ggtttttttt taattgtttc gtagttattt atttttcgtt 1080cgtaggttgg aggtaggcgt
ttttttcgta tttttttttg gtttcgtttt tttttttttt 1140tttattatat ttttatttcg
aggcgcggat acgttatcgg gaggagtttg ggttcggcgt 1200tttcgggcgt agtttttttt
tttttcgcgt tggtcgggcg gggggtggcg gcgcggttgt 1260cgggaatttt cgataggggt
cgttggacgt tgcgcggaga tcgaggttag cgtttcggag 1320attcgggaat ttaggcggag
attcgaggtt ttcgttgttc gttttttttc gtagttaggt 1380agcgtttggg agggttgttt
cgttttattt tacgcggaaa aggacggcgt agagaaaagt 1440ttgcgatttt tatatttgtg
ttttaagtag agttttcgtg gttaggaatt ttgggagggg 1500tgcgggggga acgttggtgg
tttttttaga agagttcggg gtttattttt taatttattt 1560aagtataaaa gttttgtcgt
acgtaggcga aaataaattt 160031350DNAHomo sapiens
3attttggcgt ttaatatcgt taatattagt gggttgttag gggtttcgtg ggaggcggtt
60ttagtcgggg ttttgttggc gttggcggtg ttggttatcg tgggaggtaa tttgttggtt
120atcgtggtta tcgtttggat ttcgagattt tagattatga ttaacgtgtt cgtgatttcg
180ttggtcgtag tcgatttggt gatgggattt ttggtggtgt cgtcggcggt tattttggcg
240ttgattggtt attggtcgtt gggcgttatt ggttgcgagt tgtggatttc ggtggacgtg
300ttgtgtgtga tcgttagtat cgaaattttg tgcgttttgg tcgtggatcg ttatttggtt
360gtgattaatt cgttgcgtta cggcgtattg gttattaagc gttgcgttcg gatagttgtg
420gttttggtgt gggtcgtgtc ggtcgcggtg tcgtttgcgt ttattatgag ttagtggtgg
480cgcgtagggg tcgacgtcga ggcgtagcgt tgttatttta attcgcgttg ttgtgttttc
540gtttttaata tgttttacgt gttgttgttt tttttcgttt ttttttattt tttttttttc
600gtgatgtttt tcgtttacgc gcgggttttc gtggtggtta cgcgttagtt gcgtttgttg
660cgcggggagt tgggtcgttt ttcgttcgag gagttttcgt cggcgtcgtc gcgttttttg
720gtttcggttt cggtggggac gtgcgtttcg ttcgaagggg tgttcgtttg cggtcggcgg
780ttcgcgcgtt ttttgttttt tcgggaatat cgggttttgt gtattttggg ttttattatg
840ggtattttta ttttttgttg gttgtttttt tttttggtta acgtgttgcg cgttttgggg
900ggtttttttt tagtttcggg ttcggttttt tttgttttga attggttagg ttatgttaat
960tttgttttta attcgtttat ttattgtcgt agttcggatt ttcgtagcgt ttttcgtcgt
1020tttttgtgtc gttgcggtcg tcgtttgttt tcggagtttt gcgtcgtcgt tcgttcggtt
1080tttttttttt cgggcgtttt tgcggttcgg agtagtttag cgtagtttag gttttgttaa
1140cggttcgacg ggtaggtaat cggggtagag ggatcggcgg tttagggtcg ggaagtatgc
1200gatgtgttcg tgggttaatt ttttgagtgt ggagtttatt aagagaaggt gggatggttt
1260tgtttggaga gaaaagggaa cgaggagtag cgaattaaaa tgggatttag ggtttttttt
1320ttttcggatt tagttattag ggtagaagta
135041350DNAHomo sapiens 4tgtttttatt ttagtgattg gattcggaaa gaaaaggatt
ttgggtttta ttttggttcg 60ttatttttcg tttttttttt tttttaagta aagttatttt
attttttttt aataaatttt 120atatttaaaa agttgattta cggatatatc gtatgttttt
cgattttgag tcgtcggttt 180ttttgtttcg gttatttatt cgtcgagtcg ttggtaaagt
ttgggttgcg ttgggttgtt 240tcgggtcgta ggaacgttcg aggggaagag ggtcgggcgg
gcggcggcgt agggtttcgg 300aggtaggcga cggtcgtagc ggtatagaag acggcggaag
gcgttgcgaa agttcgggtt 360gcggtagtag atgagcgggt tgaaggtaga attggtataa
tttagttagt ttagggtaag 420gaaagtcggg ttcgggatta gagaggggtt ttttagggcg
cgtagtacgt tggttagaaa 480gaagggtaat tagtagagag tgaaggtgtt tatgatgaga
tttaaggtgt atagggttcg 540gtgttttcgg agaggtagga ggcgcgcggg tcgtcggtcg
taggcgggta ttttttcggg 600cggagcgtac gtttttatcg gggtcggggt tagagagcgc
gacggcgtcg gcggagattt 660ttcgggcgga aagcggttta gtttttcgcg tagtaagcgt
agttggcgcg tagttattac 720gaaaattcgc gcgtagacga agagtattac gagaagagga
aggtagaagg agacggagga 780ggatagtagt acgtagggta tgttggaggc gaaggtatag
tagcgcgggt tggagtggta 840gcgttgcgtt tcggcgtcgg tttttacgcg ttattattgg
tttatgatgg gcgtaaacga 900tatcgcggtc gatacgattt atattaggat tatagttgtt
cgggcgtagc gtttggtgat 960tagtgcgtcg taacgtagcg ggttggttat agttaggtag
cggtttacgg ttagggcgta 1020tagggtttcg atgttggcgg ttatatatag tacgtttatc
gaggtttata gttcgtagtt 1080agtggcgttt aacggttagt ggttagttag cgttaaggtg
gtcgtcggcg gtattattag 1140gagttttatt attaggtcgg ttgcggttag cgaagttacg
aatacgttgg ttatggtttg 1200gagtttcgga gtttaggcga tggttacgat gattagtagg
ttgtttttta cggtggttag 1260tatcgttagc gttagtaggg tttcggttag ggtcgttttt
tacggaattt ttggtagttt 1320attggtgttg gcggtattgg gcgttagggt
135051600DNAHomo sapiens 5cgaaaagttt ttgaggcgtt
gcgtgtattt tattttagga tatcgtgtgt gcgcgtcgag 60ttgagtgcga ggaacgtggc
gcgagggtcg ggggatgtcg ggttgcgtgg gtgtgagttt 120tcgcgcgatc gcgatttcgc
gtttttttcg ttttcgtcgg aacgtgatcg tagtcgtatt 180ttttttttag ttttttttta
gttagacgtt tttttttagg tttttttggg cgtttattgt 240aaattttgcg attaaaatac
gtcggtgagt tcggtttatc gatagatgga ttaatcgttt 300ttttttcggt taggggagga
ggaatttttt aatttcggag tttagggagt cgggagttgt 360ttcgggacga gtttttcgga
gtttagtcgg ttgcggagtt tcggttcggg tcggtttcgg 420ggtttttttg tcggggtggg
gtgcgagttt ttgttcgatt tttttggggc ggtttaggta 480ggtttgtcgg ttttcgagga
ggtggttagg gcgttttggt ttagtaggtt ttttttcgag 540tcggggggag gggagatcgg
ttggggaagg ggtatttcga aggggtggag gtcggggcgg 600gcgggaggta agcgcgtcgc
gggcgtgagg gtaaagtttt cgaggttcgc gcggagagta 660tacgtgtatg tgcgcgcggg
gttaggtcgg ggtcggtagg atgcgttggg ttcgggggcg 720cgcggggtcg gcgtcgaagg
ggataatttt tttttttggt attatcgggg agacgttttg 780tcggtttcgg tttttgggcg
tagggacgtt ttagtttacg gagggtggag ttttttttag 840attcgggtta tcggttgggg
tttttttaac gttttgtttt tcgagttttc ggatggttcg 900ggttttacgg atttcgcgtt
ttttagtttt agtttagttt tttaggtttt ttagatttag 960cggcgtaggg ggcgggggta
ggggtagtgg gggttggagg gcgtagtcgg tttttagggt 1020ggggagagtt gcggggggag
gaggaggagg gtgtcgacgt ttgagtgggt tcgagttcga 1080gtcgtagtcg ggggagttag
ttagttttcg gttaaggtag taggttagtt ttaggaaggg 1140cgggcgattg agtcgaggga
gtcggcggtt gggttttttt ttcggttcgc gattttcggc 1200gtcgtcgtcg tcgttatcgt
tatcgttatc gttttcgttt tgtcgtcgtc gtcgttgtag 1260agtatcgtag tttcgtcgcg
ttttcgcgtt tcgcgtttcg cgtcgttagt cgtttgggag 1320ttcgagcgtc gagttcgggg
cggaggagag gggcgttggc gcgagagttc gggcgaggga 1380gtcgcgaagg gagaaggggg
cgggcggagg gaggagtagg gagagtggga gaagggggag 1440ggagagagga gagcgaggga
gagttggaga gagcgagagt aaagagcgag cgagggagag 1500gagagagaga gagaggagag
agaaagatat acgtacgtag agatatacgg ttattggaat 1560tttattagaa aaaagtgagt
cgagtaaggg ttagcgggag 160061545DNAHomo sapiens
6ttttcgttaa tttttgttcg gtttattttt ttttaatgga attttagtga tcgtgtgttt
60ttgcgtgcgt gtgttttttt tttttttttt tttttttttt ttttttttcg ttcgtttttt
120gttttcgttt tttttagttt tttttcgttt tttttttttt gcggtttttt cgttcgggtt
180ttcgcgttag cgtttttttt tttcgtttcg ggttcggcgt tcgggttttt aggcggttgg
240cggcgcgggg cgcggggcgc gggagcgcgg cggagttacg atgttttgta gcggcggcgg
300cgataaggcg aaggcggtgg cggtggcggt ggcggcggcg gcggcgtcgg ggatcgcggg
360tcgagaggag agtttagtcg tcggtttttt cggtttaatc gttcgttttt tttgggattg
420atttgttgtt ttggtcggaa attgattggt tttttcggtt acggttcggg ttcgaattta
480tttaagcgtc ggtatttttt tttttttttt ttcgtagttt tttttatttt ggggatcggt
540tgcgtttttt aatttttatt gtttttgttt tcgttttttg cgtcgttggg tttgggaagt
600ttggggagtt gagttgaggt tggagggcgc ggagttcgtg gggttcgagt tattcggggg
660ttcggggggt agggcgttag aaaaatttta gtcggtggtt cgggtttgag gggggtttta
720tttttcgtgg gttaaggcgt ttttgcgttt aggagtcgag gtcgataaag cgttttttcg
780atggtgttag ggaaaggaat tatttttttc ggcgtcggtt tcgcgcgttt tcgaatttaa
840cgtattttgt cggtttcggt ttagtttcgc gcgtatatat acgtgtgttt ttcgcgcgga
900tttcgggaat tttgttttta cgttcgcggc gcgtttgttt ttcgttcgtt tcggttttta
960ttttttcgag atgttttttt tttagtcggt tttttttttt ttcggttcgg gaagaagttt
1020gttgggttag ggcgttttga ttattttttc ggaggtcggt aaatttgttt gaatcgtttt
1080agaggaatcg ggtaggggtt cgtattttat ttcggtagga gggtttcgag atcgattcgg
1140gtcggggttt cgtagtcggt tgggtttcga ggagttcgtt tcgaggtagt tttcggtttt
1200ttaggtttcg gggttggggg gttttttttt ttttagtcgg gaagggggcg attgatttat
1260ttgtcggtgg gtcgggttta tcggcgtgtt ttagtcgtag aatttataat aaacgtttag
1320aaggatttaa aaggaagcgt ttggttggga aagggttgga ggagaggtgc ggttgcggtt
1380acgtttcggc gagagcggga gaggcgcggg gtcgcggtcg cgcgagggtt tatatttacg
1440tagttcggta tttttcggtt ttcgcgttac gtttttcgta tttagttcgg cgcgtatata
1500cggtgttttg gggtggggta tacgtagcgt tttagaaatt tttcg
154571100DNAHomo sapiens 7gaggtattag tttttgaagg tttatttttt aatattggtt
gcgagagtaa gaatggtgtg 60taatttataa aagtcgttat tgttgtaggt aagttgtagt
aaacgattcg cgttcgagta 120ttttcgtttt cgttttcgtt gcggtttcgt ttacgacgat
tttggggaat tataagtttc 180gttatatagc ggggagcgtt cggagttcgc gtcggtttcg
tttttagttc ggtttttatt 240ttcggtttcg ttttcggttt tttttcgtcg ggttaatttc
gaagagtcgt cggtggtcgc 300ggtagacgga agtcgaacga gtttttcggc ggttgtagga
tgggggattt taaagtgaaa 360gtggcggtgc ggatacgatt tatgaatcgg cgaggtgaga
gtcgagtttt tttgggtcgt 420cggggcggag gcggtaggtg tttggcgcgt ttttttttcg
gtcgtcgtgg ggggttcggc 480ggtttcgttt ttatagttag cggcggggcg cgaggagggg
ttcggggatt ttgaaattcg 540ttttcgcgtt gagacgttcg gttttttttt tttttttttt
tttttttttg gttagtttcg 600tttttggcgt cgtcgggttt ttcgtgtcgg tttcgttgtt
tttttcgttt gcgttcgttt 660cgtttttgcg tttttttgtt ttttcgtttt tttcggaggt
tttcgagggc gttttcggtt 720ttcgcgttta gtttcgtttt ggttttttag tttcgttttt
ttttcgttag ttgttatcgt 780cgttttcgcg cgcgggtcgt tagtttttgt agttcgtttc
gggatcgttc gggatttttc 840gggatttcgc gtttcgttcg ggtcgtttaa gtttgtatcg
ttttggttcg cggcgggaag 900aagggtaggg ggttaggcgg gtgtttcgcg gcgagttttt
tttatttggg cgttttgaga 960ttggggttag gtggaggaga tgtttttttc gttgtttttg
gatagttgag aaagttttgg 1020ttttgtttga agttttattt attatttttt aataaatagt
taaagtgtta agatttttgt 1080ggaattgtat ttttttgata
110081100DNAHomo sapiens 8tgttagaaag atataatttt
ataagaattt tggtatttta gttatttatt gagagatgat 60gaatgagatt ttaggtaaaa
ttaaaatttt tttaattgtt taaaaataac gaaaagggta 120ttttttttat ttgattttaa
ttttaggacg tttaggtgga aggaattcgt cgcggggtat 180tcgtttggtt ttttgttttt
tttttcgtcg cgggttaagg cggtgtaggt ttgggcgatt 240cgggcgagac gcggggtttc
ggggggtttc gggcggtttc gaggcgggtt gtaggggttg 300gcgattcgcg cgcgggggcg
acgatgatag ttggcgggga aggagcgagg ttgaggggtt 360aggacgaggt tgggcgcgag
ggtcgagggc gttttcggga attttcgggg gagacgagag 420ggtaaaaggg cgtaggggcg
gggcgggcgt aggcggaagg ggtagcgggg tcggtacgag 480gggttcgacg gcgttaggga
cggggttggt taggggggaa gggaggggag aagagggagt 540cgggcgtttt agcgcgggag
cgggttttag ggttttcggg ttttttttcg cgtttcgtcg 600ttgattatag gggcggggtc
gtcggatttt ttacggcggt cgagggaagg gcgcgttagg 660tatttgtcgt tttcgtttcg
gcggtttagg agggttcggt ttttatttcg tcggtttatg 720ggtcgtattc gtatcgttat
ttttattttg gagtttttta ttttgtagtc gtcgaggaat 780tcgttcggtt ttcgtttgtc
gcggttatcg gcgatttttc ggggttgatt cggcgggagg 840gggtcggggg cggagtcggg
ggtggggatc gggttggggg cggggtcggc gcgagtttcg 900ggcgtttttc gttgtatggc
gggatttgta gttttttagg gtcgtcgtgg gcggggtcgt 960agcgaaggcg ggggcgggaa
tgttcgggcg cgagtcgttt gttataattt atttatagta 1020atgacggttt ttgtaaatta
tatattattt ttgttttcgt agttagtatt gagaagtaag 1080tttttaagag ttgatatttt
11009850DNAHomo sapiens
9ttgtggagcg gaggagggga ggtttggggt cgcggcggtg tgcgtttcgt tttgatcgta
60gagttttttt ttcgaggaaa gcggttggtt cggtttcggt tggtgattac gcggggtttt
120tgtttgtttg gtgcgtaggt gagggtttgt tttttcgttg cgtttcggat agtttggagg
180tgagtacgcg ttgggttttg gatcgcgagt agcgggagaa gtacgagttg gtggtcgtgt
240gtatcgtgta cgtcggcgcg cgcgaggagg tggtgatggt gtttttttcg gtgatcgtgt
300acgacgagga cgattcggcg tttatttttt tcgcgggcgt cgatatcgtt agcgtcgtgg
360tggagtttaa gcggaaggag gtgtttgttc gcgcgtgttg tggtttattt agtgtttgtt
420ttcggttata gttcgttttt cggtcggttt agtgttcgtg tagttattta atcgtgtggt
480cgattattcg cgtttttatt tgtttttcgt tttcgtttgc gtcgtttgtt ttagggggag
540gggaaggggg agttttgtta gtatttagtt gggttttgtt tcgggaggta aggattagga
600cgaggttcga gggttcgcgt ttggggtata tttgtgtcgt tgtaggcggg cgcggcgcgt
660tgttcgggcg gggagtattt gtcgggaggg tatttttttt tattagtagt tagtttttaa
720cgggagggtt tttgagtgat tacgagtaga gtcggggatt ggagaaggac gggaaggcgg
780attattttcg gcgtcgttcg tttcgttttt tttcggttcg cgttggtgga gcgcgatcgt
840tatttgttgg
85010798DNAHomo sapiens 10ttagtaggtg gcggtcgcgt tttattagcg cgagtcggag
aagggcgggg cgggcggcgt 60cggaggtgat tcgttttttc gttttttttt aattttcggt
tttgttcgtg gttatttaag 120ggttttttcg ttgggggtta attgttggtg ggagggagtg
ttttttcggt agatgttttt 180cgttcgggta gcgcgtcgcg ttcgtttgta gcggtataag
tatgttttag acgcgagttt 240tcgggtttcg ttttgttttt ttttttagga tagacggcgt
agacggaggc gaaggataaa 300tgaaagcgcg aatggtcggt tatacggttg ggtggttata
cggatattaa atcgatcgag 360aaacgaattg tggtcggaga tagatattgg gtagattata
gtacgcgcgg ataagtattt 420tttttcgttt gaattttatt acggcgttgg cggtgtcgac
gttcgcgggg aaggtgggcg 480tcgagtcgtt ttcgtcgtat acggttatcg ggaagggtat
tattattatt ttttcgcgcg 540cgtcggcgtg tacggtgtat acggttatta gttcgtattt
ttttcgttgt tcgcggttta 600gggtttagcg cgtgtttatt tttaggttgt tcggggcgta
gcggaagggt agatttttat 660ttgcgtatta agtagatagg ggtttcgcgt gattattagt
cgggatcggg ttagtcgttt 720ttttcgggaa gggggttttg cggttagagc ggggcgtata
tcgtcgcggt tttaggtttt 780ttttttttcg ttttatag
79811850DNAHomo sapiens 11atcgtttttt cgtaggggtt
ttaggattta tttagatttc gtttgttttt tttttcgcgg 60taggtttcgt tgtatcgtgt
atttttttcg cgagaagttg attttgcgga aggcgttcgt 120tattatcgtc gttatttggg
ttttggcgtt gtttattatg tgtttttcgg tcgttacgtt 180gatcgttatt cgtgaggagt
attattttat ggtggacgtt cgtaatcgtt tttattcgtt 240ttatttttgt tgggaggttt
ggttcgagaa gggtatgcgt agggtttata ttattgtgtt 300tttttcgtat atttatttgg
cgtcgttggc gtttatcgtg gttatgtacg ttcgtatcgc 360gcgtaagttt tgttaggttt
cgggttcggt tttcgggggc gaggaggttg cggattcgcg 420agtatcgcgg cgtagagcgc
gcgtggtgta tatgttggtt atggtggcgt tgttttttac 480gttgttttgg ttgtcgtttt
gggcgttgtt gttgtttatc gattacgggt agtttagcgc 540gtcgtagttg tatttggtta
tcgtttacgt tttttttttc gcgtattggt tggttttttt 600taatagtagc gttaatttta
ttatttacgg ttattttaac gagaattttc gtcgcggttt 660ttaggtcgtt tttcgcgttc
gtttttgttc gcgttcgtcg gggagttata aggaggttta 720tttcgagcgg ttcggcgggt
ttttgtatag gcgggttttc gtggtggtgc ggtttagcga 780tttcgggttg ttttttgagt
cgggttttag tagtggggtt tttaggttcg gtcgtttttc 840gttgcggaat
85012850DNAHomo sapiens
12atttcgtagc gggaggcggt cgggtttggg ggttttattg ttagggttcg atttagaggg
60tagttcggag tcgttgggtc gtattattac gaagattcgt ttgtgtagaa gttcgtcggg
120tcgttcggag taggtttttt tgtggttttt cgacgggcgc gggtagaggc gggcgcggaa
180ggcggtttgg aagtcgcggc ggaagttttc gttgaagtag tcgtagatga tggggttggc
240gttgttgttg aagaaggtta gttagtgcgc gaaggggaag gcgtagacgg tgattaggtg
300tagttgcggc gcgttgagtt gttcgtagtc gatgagtagt agtagcgttt agagcggtag
360ttaggatagc gtgaagaata gcgttattat gattagtatg tgtattacgc gcgttttgcg
420tcgcgatgtt cgcgggttcg tagttttttc gttttcgggg gtcgggttcg gggtttggta
480gagtttgcgc gcgatgcggg cgtatatgat tacgatgagc gttagcggcg ttaggtagat
540gtgcgagaag agtatagtgg tgtagatttt gcgtatgttt ttttcgggtt aggtttttta
600gtaggagtag agcgggtagg agcggttgcg ggcgtttatt atgaagtggt gttttttacg
660ggtgacggtt agcgtgacgg tcgagggata tatgatgagt agcgttaggg tttagatgac
720ggcgatggtg acgagcgttt ttcgtagggt tagtttttcg cggaaagggt gtacgatgta
780gcggaatttg tcgcggggag agagataggc gggatttggg tgggttttag ggtttttgcg
840aggggacggt
85013600DNAHomo sapiens 13tttagtttcg gaatcgcgga ttgcgtttag tgacggattt
aaatttattt ttttttttga 60tttcgtcgta ggatgacgtt ttaattttcg ggtgcgttta
ttgtttaagt gattcgtgag 120acggagcggt ttttttttag agtttcggaa gacgaagtga
tttgttttac gttcgtttcg 180tttagtttta ttcgtatacg ggggaattgc gtagaggcgg
aagagggagg ttgtcgaggg 240gtttcgagga agtttcgggt acggcgcggg ggacgtagtc
ggtttaagag cgagttggta 300ttgagtaagt agcgacggag tcggcgaaag aaggttaacg
atcgcgagcg taatcgaatg 360tataatttta attcggtatt ggacgttttg cgcggtgttt
tgtttatttt tttagacgac 420gcgaagttta ttaagatcga gacgttgcgt ttcgtttata
attatatttg ggcgttgatt 480taaacgttgc gtatagcgga ttatagtttg tacgcgttgg
agtcgtcggc gtcgtattgc 540ggggagttgg gtagtttagg cggttttttc ggggattggg
ggttttttta ttttttagtt 60014600DNAHomo sapiens 14gattggggag tagagggatt
tttagttttc gggggaatcg tttgggttgt ttagtttttc 60gtagtgcggc gtcggcggtt
ttagcgcgta taagttgtgg ttcgttatgc gtagcgtttg 120agttagcgtt tagatgtagt
tgtgggcgaa gcgtagcgtt tcgattttgg tgagtttcgc 180gtcgtttggg aaggtgggta
ggatatcgcg tagggcgttt agtgtcgagt tgaggttgtg 240tattcgattg cgttcgcggt
cgttggtttt ttttcgtcga tttcgtcgtt gtttgtttag 300tgttaattcg tttttaggtc
ggttgcgttt ttcgcgtcgt gttcggagtt ttttcggggt 360ttttcggtag tttttttttt
tcgtttttgc gtagtttttt cgtgtgcgag tggggttggg 420cggggcggac gtggggtagg
ttatttcgtt tttcgaggtt ttggggaagg atcgtttcgt 480tttacgggtt atttggatag
tgggcgtatt cgagggttga ggcgttattt tacggcgggg 540ttagagggaa gggtaagttt
gagttcgtta ttgggcgtag ttcgcgattt cgaggttagg 60015850DNAHomo sapiens
15ttagtttcgg tcgtattgta tagcgaggtc ggttcggagt tcggatgttg ggttcggttt
60cgtcgaggtt cggtttggtt gtaaagtaga ggggggcgag ggaagtcggg ttagcgggtg
120tcgcgggtag tcggcgttcg ggacggggtg tggcgtttag agcgttgttg tttttcgtag
180ttaggaggtt ggatgtcggg tttgggtgtt ttttagaagg agtcgtatta gcgacgaggg
240aagaggaatt ggtttttcgg gtagtttttt tcgttttaaa tttttttttt tcgcggaggg
300tgggcgggcg gagggaggaa gcgtagtcgg ggaacgtggc gttcgcgttt ttttcgttcg
360ggggttgcgg ttgggttgag tgtgttttta aatttgagtt tttcgttttt cgcggtgggg
420tcgggattcg cggttcgggc gggggcgggc gcggtgattg gcggtcgggt cgggttcgtt
480tttcggcgtt gggtagcggg gcgttgggga gtagcgcggc gcgtacgggt cggggcgcgt
540aggtttcgtc gtcggtgagt acgggttttt tttcgcgtgg tttcgtcggg ttcgtttggt
600ttgtttattt tcggagttat ttttgttttc gtatgggttg gcgaagttgg gaggagcgag
660ttggagttag agcgcgcgtc gggcgcgttt cgtcgttgtt tgattcggcg ttcgtagttc
720gggcgtagta cgtcggtcgt aggagtacgg atgtttttcg gagtcgcggg ttggtaggta
780tcgaagtgtt ttgttttggg gttggcgagg ggagggtaaa tttggaattt ttcgggtatt
840ttttagttcg
85016850DNAHomo sapiens 16cgggttgggg ggtgttcggg ggattttaga tttgtttttt
tttcgttagt tttagggtag 60gatatttcgg tatttgttag ttcgcggttt cggggggtat
tcgtgttttt gcggtcggcg 120tgttgcgttc gaattgcggg cgtcgagtta ggtagcgacg
gggcgcgttc ggcgcgcgtt 180ttggttttag ttcgtttttt ttaatttcgt tagtttatgc
gggggtagag gtggtttcgg 240aggtgggtag gttaggcgga ttcggcgagg ttacgcgaga
gggagttcgt gtttatcggc 300gacgggattt gcgcgtttcg gttcgtgcgc gtcgcgttgt
tttttagcgt ttcgttattt 360aacgtcgagg ggcggattcg attcggtcgt taattatcgc
gttcgttttc gttcggatcg 420cgagtttcgg ttttatcgcg aggggcgggg ggtttagatt
taaagatata tttagtttag 480tcgtagtttt cgggcgggag gaacgcgggc gttacgtttt
tcggttgcgt tttttttttt 540cgttcgttta tttttcgcga ggaggaaaag tttggggcgg
gggagattgt tcgggaagtt 600agtttttttt ttttcgtcgt tagtgcggtt ttttttggaa
gatatttaaa ttcgatattt 660agttttttgg ttgcgagagg tagtagcgtt ttgggcgtta
tatttcgttt cggacgtcgg 720ttattcgcga tattcgttgg ttcggttttt ttcgtttttt
tttgttttat agttaggtcg 780agtttcggcg ggatcgagtt tagtattcgg gtttcgggtc
ggtttcgttg tgtagtgcgg 840tcggagttgg
85017600DNAHomo sapiens 17ttttgtatag gagtagtgat
tttagtattt atttaatttt ttttcggcgt cgagtttagt 60tggagaggtt aggggtggta
gtgattggta ggaggtcggg gcggggggaa tttttaagtt 120cggcgtttgg ggttgcgggt
tcgattcgag attcgttttt tttgtaagtt tcgagtcgtt 180ggttaggttc gttattgcgt
attagtcgta ttcgcgagcg ttggttttgt cggtttgagt 240tagggtgggt agggtcggga
tttacggcgg aggtggggtc gggtcgagta gtttcggggg 300attttcgaag ttatagcgtt
ttgttttttt gtacgtttcg cgttttcggt tttcgattgg 360ttgtcgggtt tagagttcgt
ttagaattgg atcgttcgtt tgtcgttcgg gtttggtttt 420atttttagag ggagtttaga
atttggtcgt agtttttaga gattattttt atttcgtggt 480ttgcgtcgaa gttgggcgga
ggatagtggg tggttaggtt ttttcgggtt agaattcggg 540atttttgtta gttattcgtg
ttaggataga tttaagtttt taaaacgcgg atggatgtat 60018600DNAHomo sapiens
18gtatatttat tcgcgttttg ggggtttgag tttgttttgg tacgggtagt tggtaggggt
60ttcgagtttt ggttcggaag ggtttggtta tttattgttt ttcgtttaat ttcggcgtag
120gttacggggt gagggtagtt tttaaaaatt gcgattaggt tttaggtttt ttttgggggt
180ggagttagat tcgagcgata agcgaacggt ttaattttgg gcgggtttta ggttcgatag
240ttaatcggag gtcgggggcg cggagcgtgt agggaggtaa ggcgttgtag tttcggggat
300ttttcgaggt tgttcggttc ggttttattt tcgtcgtggg tttcggtttt atttatttta
360gtttaggtcg gtagagttag cgttcgcgga tgcggttggt gcgtagtagc gggtttggtt
420agcggttcgg ggtttgtagg gagggcggat ttcgggtcgg attcgtagtt ttagacgtcg
480ggtttggggg tttttttcgt ttcggttttt tgttagttat tattattttt agttttttta
540attgagttcg gcgtcgggag aggattaagt aagtgttgag gttattgttt ttgtgtaaga
600191548DNAHomo sapiens 19aggtagggat aaagtgtaag aggtaaaatt ggttgaaaag
tagaagtgta ggagtcgtta 60aggggcggga cgaataggtt cgtgggtcgg gcggagttaa
gggtgggggt cggggttttt 120ttaggtggta ttcgcggcgt tagtttttaa acgttatagc
gtttcgggcg tttaggagaa 180cgcgaacggt ttttcgcggg agcgggcgag taggaggggg
cgtcgggtta tatatatagc 240ggttcggttt cgggcgggtt tggcgtttag ggaggcgcgt
attgtttttt agagttttag 300ttttagtcgc gcgtttttcg ttcggttcgt cgttttatgt
agtcggggta gagttcggcg 360ttcgggggtt tcgtcgtttg tttttcgtat tttttcggtt
gcgtattttt gttcgaggtc 420ggtcgtgcgt tttcgcggga cgttataggc gtagttttgt
tttttagttt ttcgggcgta 480ttgatcgttt gatcgacgta cggttttcgg gtcgggatgt
cggggttcgg gacggtcgcg 540gtagcgttgt tttcggcggt tttgttggtt ttgttggcgt
tttgggcggg tcgagggggc 600gtcgtcgtat ttattgtatt taacggtacg ttggaggtcg
agttggagcg tcgttgggag 660agtttggtgg cgttttcgtt ggcgcgtttg tcggtggtag
cgtagtttaa ggaggcggtc 720gtttagagcg gcgtcggcga ttatttgttg ggtattaagc
ggttgcggcg gttttattgt 780aacgtgggta tcggttttta tttttaggcg tttttcgacg
gtcgtatcgg cggcgcgtac 840gcggatattc gcgatagtga gtggcgcggt taggcgcgaa
ggggcggggg cggggggtaa 900cggtcgtcgg gttaattcgt ttagttatat tttgagattt
tcggcgggta tttgttcggg 960ggtttcggga atcggggcgg attcgggttt cggttttttt
tgacgcgggg ttggggacgt 1020agatattttt ggtttcggta gtttagcgta atttttgagg
tcgggcgtcg tttttcgttt 1080ttagaaattc gggtttcgag cgtcgaattt tagcgttttc
gttcgtgggt atagggcgcg 1140cggtgtagtt atagggggtt cgagatacgc gtttcggttt
ggtttaggtt ggggaatcgt 1200tggggtcggg ttcgcgtttg aaggttcggg attgggtgcg
gtcgtcgggg gttttttata 1260taggtaagtt aatttgagtt agcgtaggtt tgggtttcgg
aggttttaga gggtagtttg 1320ggttttggag gtttttgggg gcggttgcgt cgggaatttt
ggttttttat ttttaatttt 1380attttagaaa tagggttttc ggaggcgaat aagtcgaggg
gcggagtggg ttagggatta 1440tttgtttcgt aatgatttgc gtttcgtttt taggtttgtt
ggagttttcg ttcgtggagc 1500ggggcgtggt gagtattttc ggcgtggtta gtcggttttt
cgtggtta 1548201600DNAHomo sapiens 20tggttacgaa gaatcggttg
gttacgtcga agatgtttat tacgtttcgt tttacgggcg 60agagttttag taggtttggg
ggcggggcgt aggttattgc ggggtaggtg atttttggtt 120tatttcgttt ttcggtttgt
tcgttttcgg ggattttatt tttggggtgg ggttggggat 180aaagggttag ggttttcggc
gtagtcgttt ttaagggttt ttagagttta agttgttttt 240tagggttttc ggagtttaag
tttgcgttag tttagattag tttgtttgtg taggggattt 300tcggcggtcg tatttagttt
cggattttta gacgcgagtt cgattttagc ggttttttag 360tttgggttag gtcggggcgc
gtgtttcggg ttttttgtgg ttgtatcgcg cgttttgtgt 420ttacgggcga aggcgttgga
attcggcgtt cggagttcga gtttttgaag gcgggaggcg 480gcgttcgatt ttaggggttg
cgttgggttg tcggagttaa gagtgtttgc gtttttagtt 540tcgcgttaga agggatcgga
gttcgagttc gtttcggttt tcggggtttt cgagtaggtg 600ttcgtcgagg gttttagagt
gtgattgagc gggttggttc ggcggtcgtt gtttttcgtt 660ttcgtttttt cgcgtttggt
cgcgttattt attgtcgcgg gtgttcgcgt gcgcgtcgtc 720gatgcggtcg tcggggagcg
tttggaggtg gaagtcgatg tttacgttgt agtagagtcg 780tcgtagtcgt ttgatgttta
gtaggtagtc gtcggcgtcg ttttggacgg tcgttttttt 840gggttgcgtt gttatcggta
ggcgcgttaa cgagagcgtt attaggtttt tttagcggcg 900ttttagttcg gtttttagcg
tgtcgttggg tgtagtgggt gcggcggcgt tttttcggtt 960cgtttagggc gttagtaagg
ttagtaggat cgtcgggagt agcgttatcg cggtcgtttc 1020gggtttcgat atttcggttc
gagggtcgtg cgtcggttag gcggttagtg cgttcgggaa 1080gttggggggt agagttgcgt
ttgtggcgtt tcgcgggagc gtacggtcga tttcgggtag 1140gagtgcgtaa tcgaggaggt
gcgggaggta agcgacgggg ttttcgggcg tcgggtttta 1200tttcggttgt atggagcggc
gagtcgggcg gaaagcgcgc ggttggagtt gggattttga 1260ggagtagtgc gcgttttttt
gagcgttagg ttcgttcgag gtcgagtcgt tatatatata 1320gttcggcgtt tttttttatt
cgttcgtttt cgcggggggt cgttcgcgtt tttttgggcg 1380ttcggggcgt tgtggcgttc
gcggttggtc gtaggtcgtt tgttaattag ggtcggggga 1440agggaggagg ttggggatta
gcgtcgcgag tgttatttgg agggatttcg gtttttattt 1500ttggtttcgt tcggtttacg
gatttgttcg tttcgttttt tggcggtttt tatatttttg 1560ttttttagtt agttttgttt
tttgtatttt gtttttgttt 1600211100DNAHomo sapiens
21agggtgaagt ttgagagttt aaatggttaa ttttataggg ttgaacgttt tagaagtcgt
60aggttcgttg gggttgattt tggtagttgt cgtggaggtg ggggtattgt tgggtaacgg
120cgcgttgttg gtcgtggtgt tgcgtacgtc gggattgcgc gacgcgtttt atttggcgta
180tttgtgcgtc gtggatttgt tggcggtcgt ttttattatg tcgttgggtt tgttggtcgt
240atcgtcgttc gggttgggtc gcgtgcgttt gggtttcgcg ttatgtcgcg tcgttcgttt
300ttttttcgtc gttttgttgt cggtttgtac gttcggggtg gtcgtatttg gtttggtacg
360ttatcgtttt atcgtgtatt cgttgcggtt aggttcgcgg tcgtcgtttg tgttcgtgtt
420tatcgtcgtg tgggtcgcgg cgggattgtt gggcgcgttt tttttgttcg gtacgtcgtt
480cgtatcgttt tttgtttttg ttcgttgttc ggttttggtt gggggtttcg ggttttttcg
540gtcgttttgg gttttgttgg ttttcgcgtt gttcgttttt ttgttgttcg gcgtttacgg
600cggtattttc gtggtggcgc gtcgcgttgt tttgaggttt ttacggtcgg cgcgcgggtt
660tcgattttat tcggattttt tggatagtcg tttttttatt ttgtcgtcgt ttcggtttcg
720tttgttcggg ggtaaggcgg ttttggtttt agcgttggtc gtgggttaat ttgtagtttg
780ttggttgttt tatggttgcg cgtgtttggc gttcgtagcg cgggtcgcgg aagtcgaagc
840ggttgttatt tgggtcgttt attcggtttt cgcggtttat ttttttttgt acgggttgtt
900gtagcgtttc gtgcgtttgg tattgggtcg tttttttcgt cgtgtattgt ttggatttgt
960gcgggtttgt atttcgtaag tttggtattc gcgggtattt ttgtaatgtt tttagagatt
1020tttagagggt tttgtcgtag gtttttttga ggttttagaa tagattttcg agttggtagg
1080agggcggagt ttcgtatatt
1100221100DNAHomo sapiens 22ggtatgcggg gtttcgtttt tttgttaatt cgggggtttg
ttttggagtt ttagaagggt 60ttacggtagg gttttttggg ggtttttgga ggtattgtaa
gagtgttcgc gggtgttagg 120tttgcggagt gtaggttcgt ataggtttag gtagtgtacg
gcgagagagg cggtttagtg 180ttaagcgtac ggggcgttgt agtagttcgt ataggaaggg
gtgagtcgcg aaggtcgagt 240aggcgattta ggtgatagtc gtttcggttt tcgcggttcg
cgttgcgggc gttaggtacg 300cgtagttata aggtagttag taggttgtaa attggtttac
ggttagcgtt ggggttaggg 360tcgttttgtt ttcgggtagg cgaggtcgga gcggcggtaa
gatggaaagg cggttattta 420gagagttcga gtggagtcgg gattcgcgcg tcggtcgtgg
gggttttagg gtagcgcgac 480gcgttattac gaagatgtcg tcgtaggcgt cgagtagtag
gagggcgggt agcgcgaagg 540ttagtagggt ttagagcggt cggaagggtt cgaggttttt
agttaggatc gagtagcgag 600taggagtagg gggcggtgcg ggcggcgtgt cgagtaggga
gagcgcgttt agtagtttcg 660tcgcggttta tacggcggtg agtacgagta taggcggcgg
tcgcgagttt ggtcgtagcg 720ggtgtacgat gaggcggtag cgtgttaggt taagtgcggt
tatttcgagc gtgtaggtcg 780gtagtagagc ggcggagagg aagcgagcgg cgcggtatgg
cgcggggttt aggcgtacgc 840ggtttagttc gggcggcggt gcggttagta ggtttagcgg
tatgatggag gcggtcgtta 900gtaggtttac gacgtatagg tgcgttaggt agagcgcgtc
gcgtagtttc ggcgtgcgta 960gtattacgat tagtagcgcg tcgttgttta gtagtgtttt
tatttttacg atagttgtta 1020ggattaattt taacgagttt gcgatttttg aggcgtttag
ttttgtggag ttggttattt 1080gggtttttag gttttatttt
110023600DNAHomo sapiens 23ggtgtcggtg ttggtgttgt
ttatggtcgc gttgtattag gtgtttaata agtggatatt 60gggttaggta atttgcgatt
tgtttatcgt tttcgacgtg ttgtgttgta ttttatttat 120tttgtatttg tgcgttatcg
cgttggatag gtattgggtt attacggatt ttatcgatta 180cgtgaataag aggacgtttc
ggcgcgtcgt tgcgtttatt tcgtttattt ggtttattgg 240tttttttatt tttatttcgt
ttatgttggg ttggcgtatt tcggaagatc gttcggattt 300cgacgtatgt attattagta
aggattatgg ttatattatt tattttattt ttggagtttt 360ttatatttcg ttgttgttta
tgttggtttt ttatgggcgt atatttcgag ttgcgcgttt 420tcgtattcgt aagacggtta
aaaaggtgga gaagatcgga gcggatattc gttatggagt 480atttttcgtt tcgtagttta
agaagagtgt gaatggagag tcggggagta ggaattggag 540gttgggcgtg gagagtaagg
ttgggggtgt tttgtgcgtt aatggcgcgg tgaggtaagg 60024600DNAHomo sapiens
24ttttgtttta tcgcgttatt ggcgtataga gtatttttag ttttgttttt tacgtttagt
60ttttagtttt tgtttttcga ttttttattt atattttttt tgggttgcgg ggcgggagat
120gttttatggc gggtgttcgt ttcggttttt tttatttttt tgatcgtttt gcggatgcgg
180aagcgcgtag ttcggaatat gcgtttatag agaattagta tgagtagtag cgggatgtag
240aaagttttaa aggtggaata gatagtgtag ttatgatttt tgttaatggt gtatgcgtcg
300gggttcgagc ggtttttcgg ggtgcgttag tttagtatgg gcgggataga gatgaggaag
360ttaataagtt aagtgagcga gatgagcgta gcggcgcgtc ggggcgtttt tttgtttacg
420tagtcgatgg ggttcgtgat ggtttagtat ttgtttagcg cgatggcgta taggtgtaag
480atggatgagg tgtagtatag tacgtcgagg gcgatgaata ggtcgtaggt tatttggttt
540agtgtttatt tgttgagtat ttgatatagc gcggttatgg gtagtattaa tatcgatatt
60025850DNAHomo sapiens 25gggatgataa gggagaaaaa tttttttacg gtttcgtttg
gttcgcggcg tttgtttgtt 60tgcgcggggt taaagttcgg cgtcgtttac gcgcggttcg
ggtgggaatt cgtagacgtg 120gggcgagtag ggtcgttggt tgtggcgggc gagcgtcggg
gcgttacgtt cgaggtcgcg 180gggtcggggt tgtaggtata gttcgagcgt ttttcgcggg
gtttggtttt tgtcgttttt 240cgtttcgtcg aatcggtatc gtcgtcgtcg gagtcgtagc
gagtttttag agtttggttg 300ttggcggtcg ggagcgtcgg gacggggcgc gaagtcggag
gtttcgggac gtggatatag 360gtaaaggtcg gcgggtcgga gtcgggcggg gcgcggcggc
ggcgtttttc ggagggattt 420ggtttcggtc gggttttatt tagtcgcggt ggttcgggtt
tttacgttgg tttaggcggg 480gacgtgttaa ggggttgggt tagggttgtc gttggtttgg
tcgtttttcg ttcggcgggt 540tttaggtgac gcggtcgcgg tttaattttc gtatttgagg
ttttcggagc ggtttcgggg 600cgcgtttatt tggaggttgg aattatatag ggtcgaaaaa
gttgagtttt ggaggcgagg 660cgttgtaggt gtggcggagg aggtcgggga aggtggggtg
ggtgttaggg gtttagtatt 720gaattttttt taggtttgag gtggggaatt gcgttttgtt
taatttcgga gtttgtgggg 780attatatagt tttttttacg gtcgattttt tttgtacggt
tttatttttt tttgtttagt 840ttattttagt
85026850DNAHomo sapiens 26attgaaatgg gttagataaa
ggaaagtgga atcgtgtaga gggaatcggt cgtggaaggg 60gttgtgtggt ttttataagt
ttcgaaatta aataagacgt agttttttat tttagatttg 120gagagggttt agtattggat
ttttggtatt tattttattt ttttcggttt ttttcgttat 180atttatagcg tttcgttttt
aggatttagt tttttcgatt ttgtgtaatt ttaattttta 240ggtgggcgcg tttcgaggtc
gtttcgagag ttttaggtgc gaaagttaag tcgcggtcgc 300gttatttgag gttcgtcggg
cgagaggcgg ttaggttagc ggtaatttta gtttagtttt 360ttggtacgtt ttcgtttggg
ttaacgtggg ggttcgggtt atcgcggttg ggtagggttc 420ggtcgaggtt aggttttttc
gagaggcgtc gtcgtcgcgt ttcgttcgat ttcgattcgt 480cggtttttat ttgtatttac
gtttcggagt tttcggtttc gcgtttcgtt tcggcgtttt 540cggtcgttag tagttaggtt
ttgaggattc gttgcggttt cggcggcggc gatgtcggtt 600cggcgagacg ggaagcgata
ggagttaaat ttcgcggaaa gcgttcgagt tgtgtttgta 660gtttcgattt cgcggtttcg
gacgtggcgt ttcggcgttc gttcgttata gttagcggtt 720ttgttcgttt tacgtttgcg
ggtttttatt cgagtcgcgc gtgggcggcg tcgggttttg 780atttcgcgta ggtagataag
cgtcgcgggt tagacggaat cgtgggaaag tttttttttt 840ttgttatttt
850271350DNAHomo sapiens
27tgaggtgtgg ggattattta tttcggtggg tttttttatt tttaggtcgg tttttttatt
60acgcgtgggt gtgggggtat tgttttcgtt gcgcgtagga atagcgggga gagttaggag
120cggagcggtt tcgggatgtt agattgagta gtgggttcgt ttgcggttat tttttaggga
180ataagttttt tttcgcggag attttgtttt ttttaaaagt ttttttgggt ttagtttagg
240gcgataggac gatttttttt gggaagggag agtttgttag tttttttttt attcgttagg
300cggtgtagtt ttttttttcg ttcggggcgc gcgtatttta gcgtcgcggg tttagcgttt
360agtagtcgcg ttttaggtcg ggtttcgggt ttcgggagtt cgtaggcgcg cgttcggtcg
420ggcgtgtcgg gagcgcgcgg cggtcggggg cggagcgtag ttagggttgc gcggcgcgtt
480tcggttttcg ttcgttttta gtcgggtttt ttagcggtcg gcgggacggt tttcggttgt
540agtttgttcg ttcgtttcgc gcgggggtcg agtcgcgaag cgcgtttgcg attcggcgtt
600cgggcgcgtt ggagaggacg cgaggagtta tgaggcgtta gtttgcgaag gtggcggcgt
660tgttgttcgg gttgtttttg gaggtagggg tcggggatcg ggtgttgtcg gaggcgcggc
720gtttattatg ttggcggttg ggggcgcgta gtttcgaggc gttttagagg attttgtttg
780ggagcgtaga cggtggagcg acggggagtt atagttttgc gcgtttttcg gagttgggag
840gtgcgggatt ttggtgacgg ggaggttttc gtttcggttc gcgtttttcg tcgttttttc
900ggttttcgta tttcgttttt attttgcggg tgagcgcgtt tttcgcgtcg atcgttttcg
960ttagttcggg gtgatttttg tgtatcgttc gttttttttt ttcgtcgtag agggtcgagg
1020atcggatgga ttcggggttg ggcgggggtg gttttcgggc gcggcgtagg cgcggagagt
1080tcggggcgtc gggtagtttg gggttaggaa aggatgggtg tcgagtcggg gtgaggggag
1140cgggcggagg ggattgtggg gaagtgtcgc gggagtgtcg ggagttgtgg aggtgagtag
1200cgggaggagg cgttttcgcg tgtgaaaatg aagtgtagtt tttaggtgcg gggaggaaat
1260tttgcggaga gtttggttgg gtgggggtgc ggagtcgaag tcggcgggga atttgttgag
1320cggttttcgg gtgcgagcgt tcgtgatcgt
1350281350DNAHomo sapiens 28gcggttacgg gcgttcgtat tcggaagtcg tttaataagt
ttttcgtcgg tttcggtttc 60gtatttttat ttagttaggt ttttcgtaga attttttttt
cgtatttaaa ggttgtattt 120tatttttata cgcgggaacg ttttttttcg ttgtttattt
ttataatttt cggtattttc 180gcgatatttt tttatagttt ttttcgttcg ttttttttat
ttcggttcgg tatttatttt 240tttttaattt taaattgttc ggcgtttcgg gtttttcgcg
tttgcgtcgc gttcgaggat 300tattttcgtt taatttcggg tttattcgat tttcggtttt
ttgcggcggg gagagggggc 360ggacggtgta taaaggttat ttcgagttaa cggaggcggt
cggcgcggga aacgcgttta 420ttcgtagggt gggggcgggg tgcgaaaatc gaaggaacga
cggaaggcgc ggatcggggc 480gggagttttt tcgttattag ggtttcgtat tttttagttt
cgggaggcgc gtagggttgt 540ggtttttcgt cgttttatcg tttgcgtttt taggtaaggt
tttttggggc gtttcggaat 600tgcgcgtttt tagtcgttag tatggtgggc gtcgcgtttt
cggtagtatt cggttttcgg 660tttttatttt taagagtagt tcgagtagta gcgtcgttat
tttcgtaggt tggcgtttta 720tggtttttcg cgtttttttt agcgcgttcg gacgtcgggt
cgtaggcgcg tttcgcgatt 780cggttttcgc gcggggcggg cgggtagatt gtagtcggga
gtcgtttcgt cgatcgttgg 840ggggttcggt tgggagcggg cgggagtcgg ggcgcgtcgc
gtagttttgg ttgcgtttcg 900ttttcggtcg tcgcgcgttt tcgatacgtt cggtcgggcg
cgcgtttgcg ggttttcgga 960attcgaggtt cggtttgggg cgcggttgtt gggcgttagg
ttcgcgacgt tgaggtgcgc 1020gcgtttcggg cgggaggagg ggttgtatcg tttggcgaat
gggaggggga ttggtaggtt 1080tttttttttt aagggaggtc gttttgtcgt tttagattaa
atttaggaag gtttttaaaa 1140gaagtagagt tttcgcgggg ggaagtttgt tttttgagag
gtggtcgtag acgaatttat 1200tgtttagttt ggtatttcga agtcgtttcg tttttggttt
ttttcgttgt ttttgcgcgt 1260agcgggggta gtgtttttat atttacgcgt gatgggaagg
tcggtttggg ggtgggaagg 1320tttatcgaaa tagatggttt ttatatttta
1350291100DNAHomo sapiens 29aatttagaaa taaataaata
tatatgtata cgtatataaa tatattttaa attaaaaaat 60atttttagat agtggtatgt
attatattta gaaattaata acgaagtaaa ttatgggatg 120ttatttacgt ttgttttaaa
ggtatcgaat ttataaatta ttttaggtgc ggagtaggat 180aggttgaaaa taggaatgat
atgaattcgc gcggaatagt tgtcggcgcg gtgtttaggg 240cggtatttcg ttcggtttcg
gtttttttag ttttgggttc gatttttatt acgtttttgt 300ttcgacgcga acgcggagtt
cgagcgcgcg ttacgtcgtg tggggtcgaa gaggttgtta 360tttagaggcg gagtgcgggt
tcgcgagggt ttttattcga ttttcgtttt cgttagtatt 420tacggattcg cgttttcgtc
gcgcgtcgat tcgggagtag tatcgttttc ggtataggag 480ttttacgcgt tttttattta
ataggaagtt gggtggaagt agcgcggatt tacggtatat 540cgaacgtatt ttaatagaat
tcgacgtaga tacgcgtttt taatcggcgg agatattggt 600agggttagaa acgcgcgtag
cgggggcggg aggtcggtaa gtttttcgtt tttgttcgag 660atttcgtttc ggttcggttt
cgtttttttt tttgtttttt ttttttgtac gtacgggttt 720cgtttttcgc gcgacgtttt
ttgttgattc ggaaacggat ttttcggagt cgaggttcgt 780tcgggtgagt gtttttcgtt
ttttgtggtt aaatttagtt acgtagtttt ttttttgcgg 840cgttttttat attcggggtt
tgttggtttt cgcggatgtt ataggttcgg taatcgtttt 900tttgtcggcg gggagtttcg
cgacgttcgg aaatgtttcg aagtttgtcg tttagttgtt 960agatttgcgt ttgtgttcgg
tttcgttatt gaggtcgttt ttgttcggtt tttttatttt 1020agtttttttt atcgttcgtt
tattttatcg cgcgcggttt taggtttcga ttcggtatgt 1080ggtttgtttt ttatcgtttt
1100301100DNAHomo sapiens
30gggacgatgg aagataagtt atatgtcgaa tcgggatttg aggtcgcgcg cgataggatg
60ggcggacggt gaagagaatt agggtggaag ggtcggatag gggcgatttt agtgacggaa
120tcggatatag acgtagattt ggtagttggg cgataggttt cggagtattt tcgggcgtcg
180cgggattttt cgtcgatagg agggcggttg tcgagtttgt gatattcgcg gagattagta
240gatttcgggt gtggaggacg tcgtaggaag ggaattgcgt ggttgggttt ggttataaaa
300agcggagggt atttattcga gcggatttcg gtttcggaga attcgttttc gggttaataa
360aaaacgtcgc gcgaggggcg gggttcgtac gtgtagggag gggaggtaga gaaaaaggcg
420gggtcgggtc ggggcggggt ttcgggtagg ggcggggagt ttatcgattt ttcgttttcg
480ttgcgcgcgt ttttggtttt gttagtgttt tcgtcggttg aaagcgcgtg tttgcgtcgg
540gttttgttgg agtgcgttcg gtgtgtcgtg ggttcgcgtt gtttttattt aattttttgt
600taggtaagag gcgcgtgagg tttttgtgtc gggggcggtg ttgttttcga gtcggcgcgc
660ggcggggacg cgagttcgta ggtgttggcg ggagcgagag tcgggtgggg attttcgcga
720gttcgtattt cgtttttggg tagtagtttt ttcggtttta tacggcgtga cgcgcgttcg
780ggtttcgcgt tcgcgtcgag gtagaggcgt agtaggggtc gggtttaggg ttggaggggt
840cgggatcggg cggggtgtcg ttttggatat cgcgtcggta gttgtttcgc gcgggtttat
900gttattttta tttttaattt gttttgtttc gtatttgaga tgatttataa attcggtatt
960tttgggatag gcgtggatga tattttataa tttatttcgt tattaatttt taaatgtaat
1020atatattatt atttaaaagt attttttaat ttgaaatata tttgtatacg tatatatgta
1080tatttattta tttttgaatt
1100311350DNAHomo sapiens 31tgcgcgttgt tgcgttgagg tcgaatgaag cgtagtacgg
tgcgggtagt tcgaggtttc 60gaggttgggt tttgtttgtt tgggattgcg tcgtgtttag
tttcggtttt ttttttgtgg 120gtaaggatgg ttgagtttag tttttacggt agcggttttt
tgtgttatta gtagtttttt 180ttttgcgttt ttcgtttttt ttttttagat tggatttttt
ttttttttcg cgtttttttt 240ttcgtatttt ttattcgttg gttttttttt tagttgtttt
ttttttaggt tttttttggt 300tgcgcgcgtt ttttttttcg tttttttttt tttcgtagtt
tcgtcgtttt ggtgtttttt 360tgttcggttc ggtcggcgtt cgttttcggt ttcggtttcg
ttagttcggg ttttcgcgtt 420cggagtagtt tagttttgta gtggttcggg attcgatgtt
atgagaggga agcgagtcgg 480gcgtttagat ttttaggagg cgtcggatgc gcggcgggtt
ttgggatcgg gttttttttt 540cggttcgttt tgttttcggg tgattatttg gtttcgttta
tagttttgtt tttttcggag 600gagttatcgg tgtcgcgtgc gtgtggagta tttgtagata
tgattgcgtg gaggagattt 660tagtcgttgt ttttgttttt cgggttgttg gtgttgtgcg
cgaggttttt tattgtagcg 720aagggtaaga cggatttgtt tttggtcggg gaggcggtag
agttttcgga ggtttcgtgt 780gcggacgcga gtgtgcgttt tggggatcgt agggtacgga
gtggtcgttt ttgttcggcg 840ttgttttatc gtcgaagttc ggggaacgcg atgtacggga
gggagttttt atcgcgtttt 900ttttagtttt tttgggtttt cgttttattt cgttattttt
tttttttttt ttgggtttat 960aggagagatt tttttttttc ggtagtatag ggtgttaagg
agaaaggaat ttaatacgag 1020ttgggttgga attgtgtttc gtcggggcgg tgttgttttt
ttcgagacgt ggattttacg 1080ggtcggggtg gttgaggggt agtttttagg attttttttt
cggattcgac gcgtttggga 1140aagcgtttcg ggtgaagtcg gtttggaaag ttcgggtttt
ttacgggggt tttggtatta 1200ataggtaaag gttttcgtcg gttcggtttt ttcgtattta
tatattttat tttttttttt 1260tttttttttt ttttaacgtt tttagtcggc gaggagtagt
tgtttttaga aggtcgtttt 1320cgtttttttt tttttcggat ttcgtttttt
1350321350DNAHomo sapiens 32aaggagcgaa gttcggggga
gaggaaagcg ggggcgattt tttagaggta gttatttttc 60gtcggttgag gacgttggag
agggaaggag gagaggagga atggggtgta tgggtgcgag 120gaggtcgggt cggcggagat
ttttgtttat tggtattaaa attttcgtag agagttcgaa 180ttttttaggt cggttttatt
cgggacgttt ttttaggcgc gtcgggttcg gggagaaagt 240tttgggaatt gttttttagt
tatttcgatt cgtggagttt acgtttcgga ggaggtaata 300tcgtttcggc ggagtatagt
tttagtttaa ttcgtattgg gttttttttt ttttgatatt 360ttgtattgtc gagaaaaaga
gatttttttt gtgagtttaa gagaggggga aggaatggcg 420gggtggggcg ggggtttagg
agggttgggg agagcgcgat ggaagttttt tttcgtgtat 480cgcgtttttc gagtttcggc
gatggagtag cgtcgggtag aggcggttat ttcgtatttt 540gcggttttta aaacgtatat
tcgcgttcgt atacggggtt ttcgagggtt ttatcgtttt 600ttcggttagg agtaagttcg
ttttattttt cgttgtagtg aggagtttcg cgtatagtat 660tagtagttcg agaagtagga
gtagcgattg gaattttttt tacgtagtta tgtttgtaga 720tattttatac gtacgcgata
tcgatggttt tttcgaggaa ggtagggtta tgagcggagt 780taaataatta ttcgagggta
aggcgagtcg gagagagagt tcggttttaa gattcgtcgc 840gtattcgacg ttttttgaag
gtttgggcgt tcggttcgtt ttttttttat agtatcgggt 900ttcgagttat tgtagggttg
agttgtttcg agcgcggaga ttcgggttgg cggggtcggg 960gtcggggacg agcgtcggtc
gagtcgggta ggaaggtatt aaggcggcga ggttgcggga 1020gggggagaag cggggagagg
agcgcgcgta gttaggagag atttggagag gaggtagttg 1080gagagagagt tagcgagtgg
gagatgcggg gaggggggcg cgggggggag gagagattta 1140gtttagagag aaaaggcgga
gagcgtagaa gaagggttgt tagtggtata aggagtcgtt 1200gtcgtggagg ttggatttaa
ttatttttat ttatagagag gggatcgagg ttgggtacgg 1260cgtagtttta gatagataga
gtttagtttc ggggtttcgg gttgttcgta tcgtgttgcg 1320ttttattcgg ttttagcgta
gtagcgcgta 135033850DNAHomo sapiens
33gattttttgg gttaggatat gtgagagttg cgtaggtttg ggttcggcgt ggcggaggtg
60cgcgagagcg gttagaagag ggcgttagag agttaggcgc ggttcgcgga ggagttcgcg
120tcggttttta tatttagttt cgcgtcgcgc ggatttatcg agttcgcgtt tagacgtttt
180agttttatcg agaggtcgtt cgggtcgtgt tttttttttt ttttaggtgt aggtagagtt
240ttcgagttat ggttagtttt ttcggtagtt tcgaagttat tggtaagttt cgaggtaggg
300atggtcggtt taggagggag gaggacgacg tttttttcga agagaagagg ttggggttgt
360agttggaggg gggaagcgta tagttcgagg attgcgagaa cggggaggac gcgtcgcggt
420taggtaggga ggagatcggt atttagatag gtggcgatcg tagaggagta agtgacgcgg
480gcgttggggt tcgggggtgt cgggggcgtc ggtaggggcg gcgggaggtt tcgtggtcgg
540tttcgggttg aagttggtat tttagcggta atttcgaagg gcgcggagtg atagcgcgtg
600acggttttcg agacgttagt tgtcgttttt cggttgtgtg gttttgattt tttgattttt
660ttacgacgtc gttggttggg agatttattg gattttgcgg ttggttaaaa agagaggggt
720agtttcgcgt tttgggggtt tttagtaggg gaagtggcgg gtgttgcgtt gggtattttg
780tttggggtat ttgtttggga ttttgttggt gttttttatt tggcgagggg ttagtggtgg
840gggtaggggg
85034850DNAHomo sapiens 34ttttttattt ttattattgg tttttcgtta ggtgagaggt
attaataggg ttttagatag 60atgttttaga taggatgttt agcgtaatat tcgttatttt
ttttgttagg ggtttttagg 120acgcggggtt gttttttttt ttttggttag tcgtagagtt
tagtgggttt tttagttagc 180gacgtcgtgg gagaattagg aagttaaagt tatatagtcg
agaagcggta gttggcgttt 240cggaggtcgt tacgcgttgt tatttcgcgt ttttcggagt
tgtcgttaaa atattaattt 300taattcgggg tcggttacgg agtttttcgt cgtttttatc
ggcgttttcg gtattttcgg 360attttagcgt tcgcgttatt tatttttttg cggtcgttat
ttgtttgggt gtcggttttt 420tttttgtttg gtcgcggcgc gtttttttcg ttttcgtagt
tttcgggttg tgcgtttttt 480ttttttagtt atagttttag tttttttttt tcgggaggga
cgtcgttttt tttttttttg 540ggtcggttat ttttgtttcg gggtttgtta gtggtttcgg
agttgtcgga agggttggtt 600atggttcggg ggttttgttt gtatttggag aagaggaagg
atacggttcg agcggttttt 660cggtggagtt ggggcgtttg agcgcgggtt cggtgggttc
gcgcggcgcg gagttgggta 720taggggtcgg cgcgggtttt ttcgcgggtc gcgtttggtt
ttttggcgtt tttttttggt 780cgttttcgcg tattttcgtt acgtcgggtt taggtttgcg
tagtttttat atgttttggt 840ttaggaggtt
850351100DNAHomo sapiens 35tcggcgttta ggtgacgttg
attttgttgg tttatcgttt tgggggttat ttaatttttt 60agcgatgttt tttagttggg
gaggttaaga agtgtttcgt ttaaggtttt ttaatattcg 120atttttagat ttttaatttt
gggttagtta tatcgtaaat ttttttagtt gttttttttg 180cgttttgcgt ttttttttta
cgttatttgt tagggagtcg ttaaatagta agatcgcgcg 240ttttgcggtt ttagagtgcg
gatttcggtc gcgtgcggtt ttgatcgcgt cgttttattt 300ttggcggggt tacgtacgga
cgttatggtt ggcgtcgcgg agtcgggcga tgcgcgcgga 360ttttttcggg gttttgattg
tttttgagtt ttttttgcgg ggggcgtgcg cggttcgttt 420ttcgcggcgt tacgcggttt
tttttcggtc ggggattggt gcgtcgggcg gggcggggcg 480gggcgggata aaggcgcggg
gtttggttgc gcggggtttg cgggtagttt taattttggg 540ttcgtagttt gcgttgggtg
cgtaggaagg ttagtgtggg ggtcgttcga tatttttttt 600tcgcggaggt gggagtcgag
ttatattttg gagtggggat tggtcgcgga gcgggttgtt 660tagggtcggt cgaggtcggg
gcgagttttg cgcggcgttg gagattttgt attttcgggc 720gcgcgtaggg ttttcggtcg
tggtcgtaga gttaggaggg gcggtttcgg agttcggcgc 780ggggagggtt taggcgtagt
cggggttggt agggcgcgat attcgttttt ttttattttt 840gaaagggttt tttacgtcga
gaagaggggc gggtatggtc ggttcggcga aatcggtttg 900tatagatttt gggaagttat
cgtttgcgga gggtgggatt ttatagtttg tttatttgtt 960taggttgaga tttcgtgttt
tagttttgga tgttttacgg gtttttcgtt tcgggtagcg 1020gcgtacggga ggagaagatt
ttcggtttgt agttagattt ttttttgaga ttttttttag 1080tttaggttta gagttttggg
1100361100DNAHomo sapiens
36tttaaagttt taagtttgag ttagggaggg ttttagaggg aggtttgatt gtagatcggg
60agtttttttt tttcgtgcgt cgttgttcgg gacgagaaat tcgtggggta tttaggatta
120ggatacgagg ttttagtttg ggtaggtgga taagttgtgg ggttttattt ttcgtaggcg
180atggtttttt aaagtttgta taaatcggtt tcgtcgggtc ggttatgttc gttttttttt
240tcggcgtggg aagttttttt aaaagtggag gggagcgagt gtcgcgtttt gttaatttcg
300attgcgtttg ggtttttttc gcgtcgggtt tcggagtcgt tttttttgat tttgcgatta
360cggtcgggga ttttgcgcgc gttcgggaat gtagagtttt tagcgtcgcg tagggttcgt
420ttcgatttcg gtcggttttg ggtaattcgt ttcgcggtta gtttttattt taagatgtgg
480ttcggttttt attttcgcgg gggggaaatg tcgggcgatt tttatattga tttttttgcg
540tatttagcgt aaattacgaa tttagagttg gagttgttcg tagatttcgc gtagttagat
600ttcgcgtttt tatttcgttt cgtttcgttt cgttcggcgt attaattttc ggtcgaggag
660gggtcgcgtg gcgtcgcggg gggcgggtcg cgtacgtttt tcgtagggag gatttaggga
720tagttagggt ttcgggagag ttcgcgcgta tcgttcggtt tcgcggcgtt agttatggcg
780ttcgtgcgtg gtttcgttag ggatggggcg acgcggttag agtcgtacgc gatcgaaatt
840cgtattttgg agtcgtagag cgcgcggttt tgttgtttag cggttttttg gtaagtgacg
900tggggaagaa acgtagggcg taggagagat agttggaaag gtttgcggtg tagttggttt
960aggattgagg gtttggaggt cgggtgttgg aagattttga gcgaggtatt ttttggtttt
1020tttagttggg aggtatcgtt gaaaaattag gtgattttta agacggtaga ttagtagagt
1080tagcgttatt tgggcgtcgg
1100371100DNAHomo sapiens 37aaagttaagc gtcgtcgtta tttaaggtat tgcgttgatg
cgttgcgggt cgattaggtg 60ttttcgtcgg ggcgtttttt tttacgtagg aagggttacg
tcgagagagg taggtaataa 120gggtacggtt ggaggtcgga aggttatttc gttttcggcg
gggcgggcgc ggtttagttt 180tatttttcgg gtacgttcgg gcggggcgat tgtagggaac
ggggcgggga ggcgatagtt 240ttcggtttcg tcgcgcgtta gttcgttttc gttgttcgga
ggcgtcgtag gtttgggttt 300tcggatagtt gagttcgagc gtcgtttttc gaaaggtgaa
ggcggttcgg ggaggcgggg 360acggtgacgg gggcgggggt cgcgggcggt ttttcgacgg
ttgtcgcggg gttagtttaa 420agttttcgat tttcggtagt tgcgtttttc gcgcggggcg
tcggagtagg gcgggttaag 480ttggtttgcg gtcgcggcgg gaagaagggt tagcgaagta
ttttcgatcg ggtttaggcg 540tcggacgtcg gggggcgttt cgttgtaatt tttttttgga
agtttcgata cgagtttcgg 600ttcgcgcgcg cgttttttta cggttacgcg cgtattttgt
cgttcgtatt ttcgcgcgtt 660tttcgtttat tttttttttt tttttttatt tttatatttt
aaaataggtt aaggggtgga 720agttatattt ggtgtagttt tcggttttga tgtaaaagta
gtttttgttt ttggttgcgg 780gatagcgttg tgattattcg taacgggaga gttgttgtta
gtcgttatat cgtgcggaaa 840gcgtcggcga tcggagtatt gataatggtt tgtatagggg
agcggagaga agtttttgtt 900gcgttttaga ttcgttgttt cggcgttcgt tcgtagggag
gagggggcgc gataggtcgt 960ttagcgcgtg tttcggagtt cgcgttcggg tttggtcgtt
tgggtgagtt tttgttcgtt 1020ttttgttttt ttagtagttc ggggtggttg tttattttgt
aaatagtttt gtaatacgat 1080taaaataggc gagatagtta
1100381100DNAHomo sapiens 38tggttgtttc gtttgttttg
atcgtattgt aaggttgttt gtaaggtaaa tagttatttc 60gggttattgg aaaggtaggg
gacgagtagg aatttattta ggcggttaga ttcgggcgcg 120ggtttcgggg tacgcgttag
acgatttgtc gcgttttttt ttttttgcgg gcgggcgtcg 180aggtagcgga tttagggcgt
aatagaagtt ttttttcgtt tttttatgta gattattgtt 240agtgtttcgg tcgtcggcgt
ttttcgtacg gtgtggcgat tggtagtagt tttttcgttg 300cgagtagtta tagcgttgtt
tcgtagttag gggtaaaagt tgtttttgta ttagagtcga 360gggttgtatt aggtgtaatt
tttatttttt gatttatttt agagtgtgag gatgaaagga 420agaggaaaaa atagacggag
ggcgcgcggg ggtgcgggcg gtagggtgcg cgcgtggtcg 480tgggggagcg cgcgcgcggg
tcggggttcg tgtcggggtt tttaaagaga agttgtagcg 540aggcgttttt cggcgttcgg
cgtttgggtt cggtcggggg tgtttcgtta gttttttttt 600tcgtcgcggt cgtaggttag
tttggttcgt tttatttcgg cgtttcgcgc gggaagcgta 660gttatcgggg atcgggggtt
ttgggttggt ttcgcgatag tcgtcgggag atcgttcgcg 720gttttcgttt tcgttatcgt
tttcgttttt tcgggtcgtt tttatttttc gggaggcggc 780gttcgggttt agttgttcgg
gaatttaggt ttgcggcgtt ttcgggtagc gaaggcgggt 840tggcgcgcgg cggagtcggg
gattgtcgtt ttttcgtttc gttttttgta atcgtttcgt 900tcgaacgtgt tcgggaagtg
aggttgggtc gcgttcgttt cgtcggggac ggggtgattt 960ttcggttttt agtcgtgttt
ttgttgtttg tttttttcgg cgtggttttt tttgcgtagg 1020agaagacgtt tcggcgggag
tatttggtcg gttcgtagcg tattagcgta gtattttggg 1080tgacgacgac gtttggtttt
110039600DNAHomo sapiens
39gcgattttag aggagtaatc gggttttaat tttttgcgtt cgttttgtta taattttttt
60ttatttattt ttattttatt tttataatat tttttattgg gggggttttt tgtgtttcgg
120attttttttt ttatggtttt tttagtcgaa gtcgggggtt ttttgggcgg tttggagggt
180ttgggttagt aggtgggttc gtattttttg ttgttttttg tcggggagcg gtcgtcgttg
240ttgggcgagc gtaggagcgc ggcggagcgg agcgcgcgcg gcgggtcggg ggttgcgtag
300ttggcgtatt tgtacggtat tttgcgtcgt cggtagtttt attgtcgtat cggtttttat
360ttgtagattt tgttcgacgg tagcgtgtag ggtattcggt aggattatag ttttttcggt
420acgtattagt atttcgattt tatttttatt tgcgttttag ttcggttttt cgtttttttt
480ttttgtattt ttttttttgt ttgttaaggg cgttatcgtc gcgcggagtt cggagttttt
540ttggatttat tcggtgtaag acgtaggttg gggttgaagg gttggttaga gtagtcgcgg
60040600DNAHomo sapiens 40tcgcggttgt tttggttagt tttttagttt tagtttgcgt
tttgtatcgg atgggtttag 60gggagtttcg ggtttcgcgc ggcgatgacg tttttggtag
gtaaagaggg aggtgtaagg 120ggagggaacg aggagtcgag ttggggcgta gatgggggtg
gggtcgggat gttagtacgt 180atcgaagagg ttgtggtttt gtcgggtgtt ttgtacgttg
tcgtcgggta ggatttgtag 240gtggaagtcg gtgcggtaat agagttgtcg gcggcgtagg
atgtcgtgta ggtgcgttag 300ttgcgtagtt ttcggttcgt cgcgcgcgtt tcgtttcgtc
gcgtttttgc gttcgtttag 360tagcggcggt cgtttttcgg taggaggtaa taggaaatgc
gaatttattt gttggtttaa 420gttttttagg tcgtttagaa agttttcgat ttcggttaag
ggagttatgg agggggagat 480tcggaatata aaagattttt ttagtaaaga gtgttgtggg
ggtgggatgg aggtggatag 540agaaaaatta tagtaaaacg agcgtaaaaa gttaaggttc
ggttattttt ttgaggtcgt 600411100DNAHomo sapiens 41tatattttat ttgtgtcgta
tatgtgaaga tataattgta aatcgtttac gattttgagt 60taagattttg agttttttga
ggttaggaga tcgttaggga atgtgagtgt tttagacggg 120cgttgagttt agttcggaga
tttatttcgt tcgtagtagc ggcgcgggtt ttagagagtt 180tcgtattcgg tcgcgtttta
gttacgttga ttcggttgtg ttcgtagtgt cgcgttgtcg 240cgtagttagg tgtcgtcggg
ttggcgcggt tatttatgat tgcgtggttg ggttgggggt 300tcggggtcgg ggagtagtcg
ggattcgtcg ttttttttat gattttttcg ggtcgaatta 360cgggatcgtt acgttgaagg
tggcgtcgcg ggttttcggg gtcgcgcgag tgtaggggtc 420gttttcggtc ggtcgcgaag
ttcgcggtat cgatttttcg cgagatttcg gcgatttttt 480ttttcgtttt cgttttttcg
ttttttgttt ttttttagtt ttggtgtggg cggttttcgt 540tatggttgcg ttgcgaaggt
ttttgtggtc gttatttcgg gtgttttttt tattttgcgt 600ttattagttt ttttttgggt
cgtgggggcg gtttgcggtg attattttgg gtttttttgg 660tcggtttttt ttttttcgag
aggatgagga gagggttgtg gcggaggcgg tatggaggcg 720gcggcggcgt tggggggagt
tgagcgtggc ggcggcggtc ggcggggggt tggtcggttt 780ggtatgttat tagttgtacg
gggattttag ggtcggttcg tcggcgatcg ggcgattttt 840aaagagcgcg gttacggagt
tcgaggattc gtttcgcggt cgggggatgt tgtttatttt 900agtggcggtt gttaaggaga
cggtgagtgc gcgagcgcgc gttatatttg cgcgggggat 960gtgattttcg tgtcgggtac
gtaggatttt ggaggttgtg gggacggtgt aagcgttgtg 1020gtcgcgggtg aggaattttt
cgtgagcgag gttgatattt aggtcggata gtttaggatt 1080cggttattta cgtattggga
1100421100DNAHomo sapiens
42ttttaatacg tgggtgatcg gattttaggt tgttcggttt aggtgttagt ttcgtttacg
60ggaagttttt tattcgcggt tatagcgttt gtatcgtttt tatagttttt agggttttgc
120gtattcggta cgaaggttat atttttcgcg taggtgtgac gcgcgttcgc gtatttatcg
180tttttttggt agtcgttatt gggatgggta gtatttttcg gtcgcggggc gggttttcgg
240gtttcgtggt cgcgtttttt gagggtcgtt cggtcgtcgg cgagtcggtt ttggggtttt
300cgtatagttg gtagtatatt aggtcgatta gtttttcgtc ggtcgtcgtc gttacgttta
360gtttttttta gcgtcgtcgt cgtttttatg tcgttttcgt tatagttttt tttttatttt
420ttcgggagga gaagggtcgg ttaggaaggt ttagggtggt tatcgtaggt cgtttttacg
480gtttaaggag gggttggtga gcgtagagtg gaggagatat tcggggtggc ggttataaga
540gttttcgtag cgtagttata gcggaggtcg tttatattag agttgggagg gggtagagaa
600cggaggggcg ggggcggggg ggggggtcgt cgaaatttcg cgagaagtcg gtgtcgcgag
660tttcgcggtc ggtcgagagc gatttttata ttcgcgcggt ttcggggatt cgcgacgtta
720tttttagcgt agcggtttcg tggttcggtt cgggaagatt atggaagagg cggcggattt
780cggttgtttt tcggtttcga atttttagtt taattacgta gttataaata atcgcgttag
840ttcggcgata tttggttacg cgatagcgcg atattgcggg tatagtcgag ttagcgtaat
900tgaggcgcgg tcgagtgcgg ggttttttgg ggttcgcgtc gttgttacgg gcggggtggg
960ttttcgagtt gggtttagcg ttcgtttggg atatttatat tttttaacgg ttttttgatt
1020ttaggaaatt taaggttttg atttaaggtc gtgaacgatt tgtaattgta tttttatata
1080tacgatataa atgaggtata
110043600DNAHomo sapiens 43gtttgggtac gcgggatagg ttgtattcgt ttgttagagg
cgttttatcg aggcgttacg 60ggtgaagttt tcggttttat ttacggggcg gggtttcggt
tcggttcgat tattgttcgc 120ggtgggggag ggggatggat tacgttacgc gttaaaggcg
atcgcgattt tttttttgta 180ggtagtttgg aaggtttttt tttttttttt acgttatttt
tttcgtggta ttgaaaagtt 240tcgttttttt tttttagttt cgtttttttc gagcgttttt
tttattgttt ggaatggtgc 300ggttttaggt cgcgggttac gcggcggagg gggcgtggtt
tgttttcggt ttagtcggtt 360tttttttgtt tttgttggag ttcggggagt ggcgttggtt
gttagagcga tgtcgggtcg 420gagttgcgtc gttttagttt ttttggttgt cgtcgttagt
tgtgtcgtcg cgtagtacgc 480gtcgtcggtg agtgagtttg agtcgaggcg tagagagggg
cgtgtaggtg cgggcgcgga 540tggaggcgta ggtgtggcgg cgcgagcggg tataaggaat
atttcgtgtt gggtagtttt 60044600DNAHomo sapiens 44gaagttgttt agtacgaggt
gttttttgta ttcgttcgcg tcgttatatt tgcgttttta 60ttcgcgttcg tatttgtacg
tttttttttg cgtttcggtt taagtttatt tatcggcggc 120gcgtgttgcg cgacggtata
gttgacggcg gtagttagga ggattaaggc gacgtaattt 180cggttcggta tcgttttagt
agttaacgtt atttttcgga ttttagtaga ggtaaagaag 240agtcggttgg gtcgggggta
ggttacgttt ttttcgtcgc gtgattcgcg atttgggatc 300gtattatttt aggtagtagg
gggaacgttc ggaggaggcg ggattgggag gagaggacgg 360ggttttttag tgttacgaaa
agggtggcgt agagaaagag agagagtttt ttaggttatt 420tgtagaagga gagtcgcgat
cgtttttggc gcgtggcgtg atttattttt tttttttatc 480gcgggtaata gtcggatcga
gtcggagttt cgtttcgtag gtggggtcgg gagttttatt 540cgtggcgttt cgatggggcg
tttttagtag gcgggtgtag tttgtttcgc gtatttaggt 60045600DNAHomo sapiens
45ggtagtgtag ttgtgggaat ttttttacgc gtacgaattt agttaacgat ttttgataga
60tttttgggag tttgattaga gatgtaaggg gtgaaggagc gttttttatc gttagggaat
120tttggggata gagcgtttcg gtcgtttgat ggtcgaggta gggtgcgatt taggatttag
180gacggcgtcg ggaattatat tatggttcgg atttttaaga ttttaaagtt cgtcgtcgtt
240atcgtcgcgg ttttgttgtt agtgagtttc ggtcgcggtt tttggttggg gaagagcgta
300tttggcgtcg ggagggggta gggagacggg gatacggtag ggatgtttgg ttttggttat
360ttgcggtcgg gtatgttcgg gtaggacgaa ttcgtcgtcg gagttagggg aagaattggg
420ttttcgggtt gggtaggagg gattcggtcg cgagggagta gagaggcggt ttttttggtt
480gtttcgagtt cgcgaaggga gggaagtttt agaatcgaga gagggaggga gttaaggtgg
540aatttataga gtgagttttt tgaagatata gagcggttgt tttttttatt aattaattaa
60046600DNAHomo sapiens 46ttaattaatt aatgagagag gtaatcgttt tgtgttttta
ggaggtttat tttatgggtt 60ttattttgat tttttttttt tttcgatttt ggaatttttt
ttttttcgcg ggttcggggt 120agttaggggg atcgtttttt tgttttttcg cggtcgggtt
ttttttgttt agttcgggga 180tttagttttt tttttgattt cgacggcgag ttcgttttgt
tcggatatgt tcggtcgtag 240gtgattaggg ttaggtattt ttgtcgtgtt ttcgtttttt
tgtttttttt cggcgttagg 300tgcgtttttt tttagttagg gatcgcggtc gggatttatt
ggtagtagga tcgcgacgat 360gacgacgacg aattttaggg ttttggggat tcgggttatg
gtatggtttt cgacgtcgtt 420ttgggttttg ggtcgtattt tgtttcggtt attaggcggt
cggggcgttt tgtttttaga 480gttttttaac ggtaggaagc gtttttttat tttttgtatt
tttggttaaa tttttaaaaa 540tttattagaa atcgttggtt gagttcgtgc gcgtggagag
gtttttatag ttgtattgtt 600471100DNAHomo sapiens 47cgtttgcgga ggattgcgtt
gacgagattt ttatttattg ttattaattt gtggtggaat 60ttgtagttgt atattggatt
tgattcgttt cgtttcgaat gacgtttgtt cggaggtagt 120gaaagtatag tcgcgtcgtt
ttaagttagt ttggatatat aaattagtac gcggtcggag 180aatttcgtaa tttttgcgtt
tataaaatat atcgacgatg ttcgatttat tttaagggtt 240gaaatttacg ggtttgagag
attataagag cgttttttat cgttatggaa taacggggat 300agaacgtttc ggtcgtttcg
ggggttcgga aaaggtacgg tttaggattt agggaggcgc 360ggggagttag gtttgggttt
cgggttttta agatttttgt gttcgttgtc gtcgcggttt 420tgttgttggt gagttttcgt
cgcggttttt ggttggggaa gagcgtgttt ggcgtttgga 480gagggtaggg agagaggggg
atacggcggg ggtgcgtggt tcgggtcgtt tgcggtcggg 540tatgttcggg taagacgtat
tagtcgtcgg agtcggggga agagatgggt tttcgggttg 600ggtaggagcg atttgggtcg
ttagggaata gagcgcgcgt tttatttggt gtaaattttc 660gaatttagtg ggggagggcg
ataaggaggg aattttcgag taagttgcgt gaagttacgg 720agaggtcgtc ggattttgat
tttgtttttt ttttttattt tttgtttttt tttttttttt 780tttttttttt tttttttttt
tttttttttt tttcgtttag tttttgtttt aatttttttt 840ttttttgcgt tttcgaatga
atttttaaag gcgtttattg tagatcgttt tgaatttgcg 900gtcggcgaag aatttttttg
tggtcgttgc ggtttagtgg tttcgtttcg tgcgcgggag 960tcgtcgcggg cgtagttgga
gaggtttttt ttttttttta gcggttgcgt ttttacgcgt 1020gcggggtcgt ttatcgttaa
tgttattgtt tggggttttt tgggaaaacg agatttagga 1080gaagggagtt gtggtatttg
1100481048DNAHomo sapiens
48taagtgttat aatttttttt ttttaaattt cgttttttta aggaatttta aataatggta
60ttggcgatga gcggtttcgt acgcgtaggg gcgtagtcgt taaggagggg aaggggtttt
120tttagttgcg ttcgcgacga ttttcgcgta cggaacggaa ttattgggtc gtagcgatta
180taggggagtt tttcgtcggt cgtaggttta aagcgatttg taatgagcgt ttttaggaat
240ttattcgaag gcgtaaaaga aaaagaaatt aaggtaggaa ttgagcgagg aaggaaggga
300gggaaagaaa ggaagaaaga gaaaaagaga aagaaataga aagtaaggaa agaaaataaa
360attaaagttc gacgattttt tcgtggtttt acgtagttta ttcgggaatt ttttttttgt
420cgtttttttt tattggattc gggaatttat attaagtgga gcgcgcgttt tgttttttgg
480cggtttaggt cgtttttgtt taattcgggg atttattttt tttttcgatt tcgacgattg
540gtgcgttttg ttcggatatg ttcggtcgta ggcgattcgg gttacgtatt ttcgtcgtgt
600ttttttttgc ggggatttat taatagtagg atcgcggcga taacgagtat aagggttttg
660gggattcggg gtttaggttt ggtttttcgc gtttttttgg gttttgggtc gtgttttttt
720cgggttttcg aagcggtcgg ggcgttttgt tttcgttgtt ttatggcggt agggaacgtt
780tttatagttt tttaggttcg tgggttttag tttttaaagt agatcgggta tcgtcggtgt
840attttgtggg cgtagagatt gcggggtttt tcggtcgcgt gttgatttat gtgtttaggt
900tgatttgggg cggcgcggtt gtatttttat tgttttcggg taggcgttat tcggggcggg
960gcgaattaga tttaatgtgt aattgtaaat tttattatag gttggtgata ataaataaga
1020gtttcgttaa cgtaattttt cgtaagcg
1048491299DNAHomo sapiens 49tgtacgttta ttgtttgttt ttttttttgt acgtttggtg
ggttttattt taggcgggtg 60ttgcgacggt ggttattgcg tttttgcgta cgcgggggta
gttttcgtcg ttattttttt 120tggcgtatat gttgagtttt tatcgcgatt cgttgtcgag
ggtagatatt attcgtagtt 180tataggtaga aggtaggtag tgtcgcgtgt cgcgttttgt
tgggtatttt cggggcgttt 240tcgtcgcgtt tagttagcgg attcgggaag tgttgtgggt
tgggggttgc ggtttcgagt 300cgggtttgta gtcgttcggg cgtttcgagt ttagggttta
gttttgcggg tgttttcgcg 360ttagtaggtt cggggtgtag cgttggtggt tgggggcgta
tttacggtcg agtcgggaag 420ggattttagc gtttagggtg tgttttcgac ggggattatt
gtttttgggt tttggtttgg 480gattgcgcgg agcgtagcgc ggaagggtgg gagtttttaa
tttttagttt tgtgaagttg 540tttatttcgg agtttgggtt tgcgtatttg taggataggt
gtaataaata atatttcgtt 600tattagattg tggaaagcgc gagatgataa tgcgcgcgaa
acgtttagcg tagtattcgg 660tatagttata gttaacggtc gttggtatta ttgtaatggt
ttggttttgg cgcgggagta 720tcggtagttg agttggtaat atcggggatt cgggtttacg
gttcggagat tagggatggg 780ttgtttcgaa gtcgcgaatt gtggtagttt tgggtttttt
agtcgcgtcg gggaagtgtt 840aagtgtttcg tttaatttcg ggttcggggt tatgatttgt
aggggagtgg gtgttaagga 900cggtagggat ttgagggtat cgttttcgag gatttggtag
cgcgttttgg gtatttagcg 960cggcgagtag gtgggtgttg cggagaggga gtttttttcg
cgttttaatt tatattttgt 1020cgtttgggta gtcgcggtcg tttacgtttt ttttcgtttg
cgggggttag acggtttttt 1080ttggggtcgg ggcgtaattt ataaacgtta atttgattcg
atttgtcgtt tgttcgtttt 1140ttgtgatttg gtgtcggggg tttttcgttt tcgcgtttgg
ggttagatag tcggtgattt 1200ttttcggaag ggttatttgg ggattagtta gattagggga
tattttcggg ggcggggtaa 1260tgagaaattt gttggagtgt tcggtttttt aatcgaaaa
1299501350DNAHomo sapiens 50ttttcggttg aggggtcgag
tattttagta aattttttat tgtttcgttt tcgagggtgt 60tttttggttt ggttggtttt
tagatgattt tttcggagag ggttatcggt tgtttgattt 120taggcgcggg agcgaagggt
tttcggtatt aggttataag gggcgggtag gcggtaggtc 180ggattagatt agcgtttgtg
gattgcgttt cggttttagg gagggtcgtt tggttttcgt 240aggcggaggg aggcgtgggc
ggtcgcggtt gtttaggcgg tagaatgtgg attgaggcgc 300ggaaggggtt tttttttcgt
agtatttatt tgttcgtcgc gttgggtgtt tagaacgcgt 360tgttaggttt tcgagggcga
tatttttaga tttttgtcgt ttttgatatt tatttttttg 420taaattatgg tttcgaattc
ggggttaagc gagatatttg atattttttc ggcgcggttg 480gaggatttaa ggttgttata
gttcgcgatt tcgggatagt ttatttttga ttttcgggtc 540gtgagttcga attttcgatg
ttattagttt agttgtcgat attttcgacg ttatatttcg 600ggatttattt atttttattc
gtagaaagaa aaaaaaatcg ttaagattaa attattatag 660taatattaac gatcgttgat
tgtggttgtg tcgggtattg cgttgagcgt ttcgcgcgta 720ttgttatttc gcgtttttta
tagtttgata ggcgaggtgt tatttattat atttatttta 780tagatgcgta gatttaggtt
tcgggataag taattttata agattggaga ttagaagttt 840ttattttttc gcgttgcgtt
tcgcgtaatt ttaaattaaa atttagagat aatggttttc 900gtcgaggata tattttgaac
gttagaattt tttttcgatt cggtcgtgga tacgttttta 960gttattaacg ttgtatttcg
agtttgttga cgcggagata ttcgtagagt taggttttgg 1020gttcgggacg ttcgggcggt
tgtaaattcg gttcggagtc gtagttttta atttatagta 1080tttttcgagt tcgttggttg
gacgcggcgg aggcgtttcg ggggtgttta gtagggcgcg 1140gtacgcggta ttgtttattt
tttgtttgta ggttgcggat gatgtttgtt ttcggtagcg 1200ggtcgcggta gaggtttagt
atgtacgtta gaggggatgg cgacgagggt tgttttcgcg 1260tacgtaggag cgtagtggtt
atcgtcgtag tattcgtttg gagtagggtt tattaggcgt 1320gtagaaggaa gggtaggtag
tgggcgtgta 135051350DNAHomo sapiens
51ttttgaaggg cggcggattt tagggttatg ttggttgttt ttagaaagta ggagttcgaa
60atcgcggggt taacgaacgt ttatattttt tgttataatt tcgttatttt tttgcgtttt
120tttttttgtt ttttgttttt ataggtaacg tttagaacga gtgttttttt cggtggggta
180ttgaggagtt tgggttgtag ttgtcgagtc gttatagtta cgttgagttc ggtttggttt
240gtatattggc gttatcgttt ggcggggagc gggattgacg cgtttttttt tttttttttt
300agtttagatt acggaggcgc ggagttttat tttttgtttt gggcgagggg
35052350DNAHomo sapiens 52tttttcgttt agggtaggag atggagtttc gcgttttcgt
gatttgggtt ggaggagagg 60gagaggagcg cgttagtttc gtttttcgtt aggcggtggc
gttagtgtgt aggttaggtc 120gggtttagcg tggttgtggc ggttcggtag ttgtagttta
ggttttttag tattttatcg 180ggagaagtat tcgttttggg cgttatttgt gggggtaggg
ggtaagggga gaggcgtagg 240ggagtggcga ggttgtagta gagaatgtgg gcgttcgttg
gtttcgcggt ttcgggtttt 300tgttttttgg ggatagttag tatggttttg aagttcgtcg
ttttttagag 35053350DNAHomo sapiens 53taattagggt tggtttattt
ttttttagtt aatttttttt tatttttagt ttttaattta 60atttatttcg tttattagtt
tttggatttt tattattttt ttcgtatttt cggtagtttt 120ggggaagttt cgtgacgtta
taggtttcgt ttttagtttc ggttcggggt tagtgcgtgt 180tgacgttatg ttgcgtgcgg
gtcggtgcgg aatcgttttt ttaatttcgc ggggtagtag 240gagttagtta gtaaagagtc
gaggtcgggc gcgcgatttt cgtttttttg tttttggtcg 300tatattttgc gtatattttt
ttttttgtat ggtggatatt attttttatt 35054350DNAHomo sapiens
54aatgaaaaat aatatttatt atgtagaaaa agagatgtgc gtaaagtgtg cggttagggg
60tagaaggacg agggtcgcgc gttcggtttc ggttttttgt taattaattt ttattgtttc
120gcggagttga aggagcgatt tcgtatcggt tcgtacgtag tatgacgtta atacgtatta
180gtttcgggtc ggagttgggg gcgggatttg tggcgttacg aagttttttt agaattgtcg
240gggatgcggg ggaggtgatg gggatttagg ggttgatggg cggggtgggt tgggttggag
300gttgggggtg aagggagatt ggttgggagg aagtgggtta attttgattg
3505522DNAArtificialPrimer 55gagcgggtag cgagagtttc gg
225623DNAArtificialPrimer 56taacgacgcg
actaccgaaa acc
235724DNAArtificialPrimer 57gattaacgtg ttcgtgattt cgtt
245825DNAArtificialPrimer 58caacgaccaa taaccaatca
acgcc 255924DNAArtificialPrimer
59atacgtcggt gagttcggtt tatc
246024DNAArtificialPrimer 60actcccgact ccctaaactc cgaa
246122DNAArtificialPrimer 61tgaatcggcg aggtgagagt
cg 226224DNAArtificialPrimer
62accgaacgtc tcaacgcgaa aacg
246324DNAArtificialPrimer 63tatcgttagc gtcgtggtgg agtt
246424DNAArtificialPrimer 64ctacacgaac actaaaccga
ccga 246525DNAArtificialPrimer
65tcggtcgtta cgttgatcgt tattc
256624DNAArtificialPrimer 66accctacgca tacccttctc gaac
246724DNAArtificialPrimer 67gtttcgagga agtttcgggt
acgg 246824DNAArtificialPrimer
68gatcgttaac cttctttcgc cgac
246921DNAArtificialPrimer 69cgaagttggg aggagcgagt t
217024DNAArtificialPrimer 70aaacatccgt actcctacga
ccga 247124DNAArtificialPrimer
71cgtattagtc gtattcgcga gcgt
247221DNAArtificialPrimer 72cgaaactact cgacccgacc c
217324DNAArtificialPrimer 73taacggtacg ttggaggtcg
agtt 247424DNAArtificialPrimer
74acgaccgcct ccttaaacta cgct
247524DNAArtificialPrimer 75tatcgtgtat tcgttgcggt tagg
247623DNAArtificialPrimer 76aacgatacga acgacgtacc
gaa 237724DNAArtificialPrimer
77tacgtgaata agaggacgtt tcgg
247823DNAArtificialPrimer 78aacgatcttc cgaaatacgc caa
237922DNAArtificialPrimer 79tcgtcgaatc ggtatcgtcg
tc 228024DNAArtificialPrimer
80acctatatcc acgtcccgaa acct
248125DNAArtificialPrimer 81cggttgtagt ttgttcgttc gtttc
258224DNAArtificialPrimer 82ctaacgcctc ataactcctc
gcgt 248324DNAArtificialPrimer
83gcgtcgattc gggagtagta tcgt
248424DNAArtificialPrimer 84ataccgtaaa tccgcgctac ttcc
248524DNAArtificialPrimer 85cgttgaggtc gaatgaagcg
tagt 248623DNAArtificialPrimer
86aaccgaaact aaacacgacg caa
238724DNAArtificialPrimer 87aagcgtatag ttcgaggatt gcga
248823DNAArtificialPrimer 88ccgcgtcact tactcctcta
cga 238924DNAArtificialPrimer
89cgttgggtgc gtaggaaggt tagt
249022DNAArtificialPrimer 90gaccgaccct aaacaacccg ct
229122DNAArtificialPrimer 91gttgcgggat agcgttgtga
tt 229224DNAArtificialPrimer
92accattatca atactccgat cgcc
249324DNAArtificialPrimer 93tttgtttgtt aagggcgtta tcgt
249422DNAArtificialPrimer 94ccgcgactac tctaaccaac
cc 229523DNAArtificialPrimer
95gggcgttgag tttagttcgg aga
239624DNAArtificialPrimer 96acgaacacaa ccgaatcaac gtaa
249722DNAArtificialPrimer 97ggcgttggtt gttagagcga
tg 229824DNAArtificialPrimer
98gactcaaact cactcaccga cgac
249924DNAArtificialPrimer 99ggtgcgattt aggatttagg acgg
2410024DNAArtificialPrimer 100gcgaccgaaa
ctcactaaca acaa
2410124DNAArtificialPrimer 101gcgatttggg tcgttaggga atag
2410225DNAArtificialPrimer 102acctctccgt
aacttcacgc aactt
2510322DNAArtificialPrimer 103ggtagtcgcg gtcgtttacg tt
2210424DNAArtificialPrimer 104acgaacaaac
gacaaatcga atca
2410524DNAArtificialPrimer 105tacgttgagt tcggtttggt ttgt
2410623DNAArtificialPrimer 106cgcgcctccg
taatctaaac taa
2310724DNAArtificialPrimer 107gtgcgtgttg acgttatgtt gcgt
2410822DNAArtificialPrimer 108cgcccgacct
cgactcttta ct
2210924DNAArtificialPrimer 109cggcgatttc ggggatttta gggc
2411025DNAArtificialPrimer 110gaccgctctt
ctaaaaaatc ccgcg
2511123DNAArtificialPrimer 111acgttcgggg tgtagcggtc gtc
2311224DNAArtificialPrimer 112ccccaatact
aaatcacgac gccg
2411325DNAArtificialPrimer 113ggtcggcgtc gtgatttagt attgg
2511424DNAArtificialPrimer 114actacgacga
cgaaactcca acga
2411526DNAArtificialPrimer 115tgtggtgatt ttggggattt tagggt
2611627DNAArtificialPrimer 116ccaaccactc
ttctaaaaaa tcccaca
2711725DNAArtificialPrimer 117gatgtttggg gtgtagtggt tgttg
2511826DNAArtificialPrimer 118ctccacccca
atactaaatc acaaca
261191300DNAHomo sapiens 119gtcaggtggg ctactccacc agggaggcct tctccccacc
cctggcccag ggcccttccg 60gatttccaga gaattctgga accaagacct tcccctttct
caccagggac ctccttgctc 120cagggcctcc cgagcgcctg gccgtgaggc agggcccaga
aggccagggc gggatccagg 180tggctggcct cacccactgg gacgtgccca acctggagac
attgcaccag gtagggctgc 240accgctctcc gagaccccgc cccgtgcttc cacttggggg
cggggaccct gcacctgacc 300agcccttcgc cccgccttcc agatgctgaa actggggagg
agcaaccggg ccaccgccgc 360caccgccatg aaccagcgca gctcccgctc gcatgccctg
gtcacgctga cgctgcgcgc 420ggcgtctcca ccgcgcgctc caggcaccgc aggtaccacg
gccggtgcct gagccctgcg 480gagtctccag agcacccgag gcccggcctt cccccatgtc
gggctcgctc gcccctctag 540gcacgctgca cctggtggac ctggcgggat ccgaacgcgc
acggaaggca ggggcggccg 600gcccgccgcg gggagaccca gacggcgccc ggcgcctgcg
ggaggcccag accataaacc 660gctcgctgct ggcgctagga ggcgtgatgg ccgcactgcg
ggcccaccgg ccgcacgtgc 720ccttccgcga ctcgcagctc acgcgactgc tgcagccggc
gctgggccca ggcaccaccg 780cggtgctgct gctgcaggtg ggcgccgggg cggggcaggt
gtgtgcgtgc cggtcgccgc 840ccacccgggc ccgcccaccc gcgcctcttg cccgcagatc
tccacgcggc cggaggatct 900cggggagaca gtctgctccc tcaagttcgc cgaccgagtg
ggtcaagtgg agctggggcc 960agcccggcgc cgcagggtcc cgcgctcctc cgggacgcct
tcttccctca gcaccgacac 1020tccgctcacc gggaccccct gcacccctac gccgtcccct
ggcagtcctc catgccccag 1080tcccgacaac ggctcgggct cggctctcgc gcccgcagag
ggcctgcccc tctagtcctg 1140ggtcgcggcc ctgcccatgg ggtctcaggc caggtctctg
ctggcagagg cggtagtaaa 1200gtccctgtac cccgtctccc agggcacaag ctccctagcc
tctttggatc cattgcccct 1260gagctcccag agtcacccct ccacctccgc agccagtgaa
13001201300DNAHomo sapiens 120ttcactggct gcggaggtgg
aggggtgact ctgggagctc aggggcaatg gatccaaaga 60ggctagggag cttgtgccct
gggagacggg gtacagggac tttactaccg cctctgccag 120cagagacctg gcctgagacc
ccatgggcag ggccgcgacc caggactaga ggggcaggcc 180ctctgcgggc gcgagagccg
agcccgagcc gttgtcggga ctggggcatg gaggactgcc 240aggggacggc gtaggggtgc
agggggtccc ggtgagcgga gtgtcggtgc tgagggaaga 300aggcgtcccg gaggagcgcg
ggaccctgcg gcgccgggct ggccccagct ccacttgacc 360cactcggtcg gcgaacttga
gggagcagac tgtctccccg agatcctccg gccgcgtgga 420gatctgcggg caagaggcgc
gggtgggcgg gcccgggtgg gcggcgaccg gcacgcacac 480acctgccccg ccccggcgcc
cacctgcagc agcagcaccg cggtggtgcc tgggcccagc 540gccggctgca gcagtcgcgt
gagctgcgag tcgcggaagg gcacgtgcgg ccggtgggcc 600cgcagtgcgg ccatcacgcc
tcctagcgcc agcagcgagc ggtttatggt ctgggcctcc 660cgcaggcgcc gggcgccgtc
tgggtctccc cgcggcgggc cggccgcccc tgccttccgt 720gcgcgttcgg atcccgccag
gtccaccagg tgcagcgtgc ctagaggggc gagcgagccc 780gacatggggg aaggccgggc
ctcgggtgct ctggagactc cgcagggctc aggcaccggc 840cgtggtacct gcggtgcctg
gagcgcgcgg tggagacgcc gcgcgcagcg tcagcgtgac 900cagggcatgc gagcgggagc
tgcgctggtt catggcggtg gcggcggtgg cccggttgct 960cctccccagt ttcagcatct
ggaaggcggg gcgaagggct ggtcaggtgc agggtccccg 1020cccccaagtg gaagcacggg
gcggggtctc ggagagcggt gcagccctac ctggtgcaat 1080gtctccaggt tgggcacgtc
ccagtgggtg aggccagcca cctggatccc gccctggcct 1140tctgggccct gcctcacggc
caggcgctcg ggaggccctg gagcaaggag gtccctggtg 1200agaaagggga aggtcttggt
tccagaattc tctggaaatc cggaagggcc ctgggccagg 1260ggtggggaga aggcctccct
ggtggagtag cccacctgac 1300121550DNAHomo sapiens
121aacacgtgta ggttgttgga attacattaa cgaatgaatg agcaaaacct tctaaaccac
60cgaccaatga aaccccgata cagaaaatcg ctgtcatgag taagttagca ctcctgaaga
120gtttgaatac tgaactggcc agagtctgcg cgccgacgcc ccccaggtgg ccggagtgac
180ccggagcagg cgtggctgtc tctcagaccc gcgcgttggg cccgaacagt ttgtccccac
240gcagctccca tataaggcgg gcccctcccc tgccccagcc agctaggtcg ccgcgctggc
300tccctggcgg cttctcaaac caacccgccg ctactgcgca tgcttggcaa gctcgcccgc
360tccttaatat cctgctccgg ctgttcctgc cacccgttgg tcaaattcgc acccagctct
420gctccagaca gagggaaaac ccagtgattt ccgggctcta gaaacaaagg gaggctatga
480ttccctgctg gccctagggg tccagggaag gttatggaaa gataattctt tgtgtaagcg
540ggttgcgtac
550122550DNAHomo sapiens 122gtacgcaacc cgcttacaca aagaattatc tttccataac
cttccctgga cccctagggc 60cagcagggaa tcatagcctc cctttgtttc tagagcccgg
aaatcactgg gttttccctc 120tgtctggagc agagctgggt gcgaatttga ccaacgggtg
gcaggaacag ccggagcagg 180atattaagga gcgggcgagc ttgccaagca tgcgcagtag
cggcgggttg gtttgagaag 240ccgccaggga gccagcgcgg cgacctagct ggctggggca
ggggaggggc ccgccttata 300tgggagctgc gtggggacaa actgttcggg cccaacgcgc
gggtctgaga gacagccacg 360cctgctccgg gtcactccgg ccacctgggg ggcgtcggcg
cgcagactct ggccagttca 420gtattcaaac tcttcaggag tgctaactta ctcatgacag
cgattttctg tatcggggtt 480tcattggtcg gtggtttaga aggttttgct cattcattcg
ttaatgtaat tccaacaacc 540tacacgtgtt
550123550DNAHomo sapiens 123cagccgaggg gcgcgcctgg
ctgatgtgtg gttgaatgga gagcggccca accctcctcc 60ttcctcctct tcttctcccc
gccctgacac ccgggcctca aacttcaacc aaagcccgtg 120cccttttcaa tttacccccc
tcgatcaaaa tgagccattc ttgtctgtcc tccgcggcgg 180cccattgtct ggcgtgatag
gtttgcagat ttgacagctg ggcgcacgca gatttgattc 240aaactcggtc tccccgagag
atgaacttgg acatcagcaa agatcccgag cactgccggc 300tggctcctag accggtctcc
cgacccagtg tagacttcgg tgccccgggc gccccccggc 360gtgcgggaag gggagcgtgt
gtcaggcgtg gggggcgggg ggtgagcagc acgactggga 420accagcggtc ccaggggttg
gggcgaaggg ctgtgtacat gttaggcttt ttttgttgtt 480gttaatttac tctcgaaaca
gccaaaatgg aggtcagctt ataaattttc taaagccagg 540tctggccggg
550124550DNAHomo sapiens
124cccggccaga cctggcttta gaaaatttat aagctgacct ccattttggc tgtttcgaga
60gtaaattaac aacaacaaaa aaagcctaac atgtacacag cccttcgccc caacccctgg
120gaccgctggt tcccagtcgt gctgctcacc ccccgccccc cacgcctgac acacgctccc
180cttcccgcac gccggggggc gcccggggca ccgaagtcta cactgggtcg ggagaccggt
240ctaggagcca gccggcagtg ctcgggatct ttgctgatgt ccaagttcat ctctcgggga
300gaccgagttt gaatcaaatc tgcgtgcgcc cagctgtcaa atctgcaaac ctatcacgcc
360agacaatggg ccgccgcgga ggacagacaa gaatggctca ttttgatcga ggggggtaaa
420ttgaaaaggg cacgggcttt ggttgaagtt tgaggcccgg gtgtcagggc ggggagaaga
480agaggaggaa ggaggagggt tgggccgctc tccattcaac cacacatcag ccaggcgcgc
540ccctcggctg
5501251050DNAHomo sapiens 125agaaactgag gtcggagtgg gggcgtgacc aggccagcct
aaggccgctg cactaatgag 60aagctgagct ctcagatttt tgcctccctg tccctgccaa
gtcgctgttt cctgggacaa 120gagggagcct cactgaaacg aactccggtc tcaggggaca
gaatcctgaa accctggctc 180tggggtccgg ggcaggggtg cgctgcctca ggacagacgg
tgaaactgag gtccagagcc 240ggacatccac cgcctgcgga gggaacgaga acgcggcgcg
tcctgccttg cgggccgagc 300ggcgccagag ccgcctcctc ccgccccccg cgctagatcc
ccccgccccg tctttgccct 360cgcgacgccg ccacctccgg aacaagccat ggtggcggcg
acggtggcag cggcgtggct 420gctcctgtgg gctgcggcct gcgcgcagca ggagcaggac
ttctacgact tcaaggcggt 480caacatccgg ggcaaactgg tgtcgctgga gaagtaccgc
ggatcggtga gtgcgcgggg 540tctggcggcg ccgctgggcc cggcctcgcc ctggcggggc
ctgctgggga cgccccgcag 600cccggtcccc cgcgcggtgt ggctccgagg acgctccagc
cgcgcggccg ccaaaccccg 660gcccccgccc cgctcggccg tgacctctgg cgcggcgccc
ccatcccgcg cccggcccgg 720cccggcccgc ggctacgtgg cacggccttg gcgcggagga
acccgaagcg ctcgcagtcg 780gcgcccactt cgctaccggc acctttgggc agcggggtcc
agaccttcgc cgggaggccg 840ggcaccactg cccagccttt gccattcacg ggtgaaaaaa
gtaaccgtag catcgtgcgg 900cctttccctc tcccgtcctc attttctgca tctggaacgg
ggagtggctg attcggagtc 960cagtgaagaa cactgtggag atcaatgtgc agggcagaga
gagagttatt tcagatgcac 1020ggagacctca cacggatcat ccctgggaga
10501261050DNAHomo sapiens 126tctcccaggg atgatccgtg
tgaggtctcc gtgcatctga aataactctc tctctgccct 60gcacattgat ctccacagtg
ttcttcactg gactccgaat cagccactcc ccgttccaga 120tgcagaaaat gaggacggga
gagggaaagg ccgcacgatg ctacggttac ttttttcacc 180cgtgaatggc aaaggctggg
cagtggtgcc cggcctcccg gcgaaggtct ggaccccgct 240gcccaaaggt gccggtagcg
aagtgggcgc cgactgcgag cgcttcgggt tcctccgcgc 300caaggccgtg ccacgtagcc
gcgggccggg ccgggccggg cgcgggatgg gggcgccgcg 360ccagaggtca cggccgagcg
gggcgggggc cggggtttgg cggccgcgcg gctggagcgt 420cctcggagcc acaccgcgcg
ggggaccggg ctgcggggcg tccccagcag gccccgccag 480ggcgaggccg ggcccagcgg
cgccgccaga ccccgcgcac tcaccgatcc gcggtacttc 540tccagcgaca ccagtttgcc
ccggatgttg accgccttga agtcgtagaa gtcctgctcc 600tgctgcgcgc aggccgcagc
ccacaggagc agccacgccg ctgccaccgt cgccgccacc 660atggcttgtt ccggaggtgg
cggcgtcgcg agggcaaaga cggggcgggg ggatctagcg 720cggggggcgg gaggaggcgg
ctctggcgcc gctcggcccg caaggcagga cgcgccgcgt 780tctcgttccc tccgcaggcg
gtggatgtcc ggctctggac ctcagtttca ccgtctgtcc 840tgaggcagcg cacccctgcc
ccggacccca gagccagggt ttcaggattc tgtcccctga 900gaccggagtt cgtttcagtg
aggctccctc ttgtcccagg aaacagcgac ttggcaggga 960cagggaggca aaaatctgag
agctcagctt ctcattagtg cagcggcctt aggctggcct 1020ggtcacgccc ccactccgac
ctcagtttct 1050127550DNAHomo sapiens
127ttctcttacg atctggcttt actctcacgc gcacagccga gtccctgggg acccagcaga
60ggtccgaagc ggagcggggc ggggcggggc tacggaagct ggcgaggccg agcccctcct
120agtgcttccg gaccttgctc cctgaacact cggaggtggc ggtggatctt actccttcca
180gccagtgagg atccagcaac ctgctccgtg cctcccgcgc ctgttggttg gaagtgacga
240ccttgaagat cggccggttg gaagtgacga ccttgaagat cggcgggcgc agcggggccg
300agggggcggg tctggcgcta ggtccagccc ctgcgtgccg ggaaccccag aggaggtcgc
360agttcagccc agctgaggcc tgtctgcaga atcgacacca accagcatca tgtccatgac
420actggggtac tgggacatcc gcggggtgag tgagggtccg ctgcactgtg ggaccgggcg
480cgtgggcggg aagtgccgag cggctgggga ccggctctag ggacggttcc ctccttaggg
540ctatctctca
550128550DNAHomo sapiens 128tgagagatag ccctaaggag ggaaccgtcc ctagagccgg
tccccagccg ctcggcactt 60cccgcccacg cgcccggtcc cacagtgcag cggaccctca
ctcaccccgc ggatgtccca 120gtaccccagt gtcatggaca tgatgctggt tggtgtcgat
tctgcagaca ggcctcagct 180gggctgaact gcgacctcct ctggggttcc cggcacgcag
gggctggacc tagcgccaga 240cccgccccct cggccccgct gcgcccgccg atcttcaagg
tcgtcacttc caaccggccg 300atcttcaagg tcgtcacttc caaccaacag gcgcgggagg
cacggagcag gttgctggat 360cctcactggc tggaaggagt aagatccacc gccacctccg
agtgttcagg gagcaaggtc 420cggaagcact aggaggggct cggcctcgcc agcttccgta
gccccgcccc gccccgctcc 480gcttcggacc tctgctgggt ccccagggac tcggctgtgc
gcgtgagagt aaagccagat 540cgtaagagaa
550129550DNAHomo sapiens 129tcttgaattg ggggcggagg
taaaaaaaaa aaaaaagtcc tcactgtggg aagctataaa 60aagcaaagag gactggggag
agagcagaga gagagaaagc gggagcccgc ggcgagcgta 120gcgcaagtcc gctccctagg
catcgctgcg ctggcagcga ttcgctgtct cttgtgagtc 180aggggacaac gcttcggggc
aactgtgagt gcgcgtgtgg gggacctcga ttctcttcag 240atctcgagga ttcggtccgg
ggacgtctcc tgatccccta ctaaagcgcc tgctaacttt 300gaaaaggagc actgtgtcct
gcaaagtttg acacataaag gataggaaaa gagaggagag 360aaaagcaact gagttgaagg
agaaggagct gatgcgggcc tcctgatcaa ttaagaggag 420agttaaaccg ccgagatccc
ggcgggacca aggaggtgcg gggcaagaag gaacggaagc 480ggtgcgatcc acagggctgg
gttttcttgc accttgggtc acgcctcctt ggcgagaaag 540cgcctcgcat
550130550DNAHomo sapiens
130atgcgaggcg ctttctcgcc aaggaggcgt gacccaaggt gcaagaaaac ccagccctgt
60ggatcgcacc gcttccgttc cttcttgccc cgcacctcct tggtcccgcc gggatctcgg
120cggtttaact ctcctcttaa ttgatcagga ggcccgcatc agctccttct ccttcaactc
180agttgctttt ctctcctctc ttttcctatc ctttatgtgt caaactttgc aggacacagt
240gctccttttc aaagttagca ggcgctttag taggggatca ggagacgtcc ccggaccgaa
300tcctcgagat ctgaagagaa tcgaggtccc ccacacgcgc actcacagtt gccccgaagc
360gttgtcccct gactcacaag agacagcgaa tcgctgccag cgcagcgatg cctagggagc
420ggacttgcgc tacgctcgcc gcgggctccc gctttctctc tctctgctct ctccccagtc
480ctctttgctt tttatagctt cccacagtga ggactttttt ttttttttta cctccgcccc
540caattcaaga
550131550DNAHomo sapiens 131cgattggctg caagggtctc ggcttggccg cggattggtc
acacccgagg gcttgaaagg 60tggctgggag cgccggacac ctcagacgga cggtggccag
ggatcaggca gcggctcagg 120cgaccctgag tgtgccccca ccccgccatg gcccggctgc
tgcaggcgtc ctgcctgctt 180tccctgctcc tggccggctt cgtctcgcag agccggggac
aagagaagtc gaaggtgagt 240gagcctccgg gccgggggcc gggagaaaaa acctagcccc
tcggtgtcca gcgctcagtg 300caatgcaccc cttttcccag gctccccgcc agatgggcaa
tccccaggtg cgagagacct 360cctgaacccc ttttgccgcc ccctccgccg ccgggacccc
gcccccgacc gtcgtcgtct 420cgtagttcca tctgttggag agccgagacc tggtgcttca
ggcgggcaga atgactaagg 480gaggaaggtc tctctccccg agctcgcact ttctccccac
tgccacctcg agggtcgcct 540tgctacatct
550132550DNAHomo sapiens 132agatgtagca aggcgaccct
cgaggtggca gtggggagaa agtgcgagct cggggagaga 60gaccttcctc ccttagtcat
tctgcccgcc tgaagcacca ggtctcggct ctccaacaga 120tggaactacg agacgacgac
ggtcgggggc ggggtcccgg cggcggaggg ggcggcaaaa 180ggggttcagg aggtctctcg
cacctgggga ttgcccatct ggcggggagc ctgggaaaag 240gggtgcattg cactgagcgc
tggacaccga ggggctaggt tttttctccc ggcccccggc 300ccggaggctc actcaccttc
gacttctctt gtccccggct ctgcgagacg aagccggcca 360ggagcaggga aagcaggcag
gacgcctgca gcagccgggc catggcgggg tgggggcaca 420ctcagggtcg cctgagccgc
tgcctgatcc ctggccaccg tccgtctgag gtgtccggcg 480ctcccagcca cctttcaagc
cctcgggtgt gaccaatccg cggccaagcc gagacccttg 540cagccaatcg
550133550DNAHomo sapiens
133aggggaactg gtatctccac agtaattact agagcagctc tggggaacgg agggttggct
60aaggaagaaa agctccccca acccttgggg cgagggagcg ttctctcaat ggagcccccc
120caactcccct ccacccccca ccagtcttcc aggaaagagg aataccctac ccggcagggc
180tgcgaaggaa ggggaaatcc aaccagagcg aaagtcgcac gcggacagct ctgccagccc
240ttggaggcat ccggcggtca cccacgggac aaagcgcggc tgcgggagcg cgcgcggggc
300attccggacc cgcgtcgagc tccgctctag agggggcggc gggcggcgac aagccggaga
360gaggaagggc caaggagcac ggccctcctg tcggcaccat cagcgggaga gtggcgagcg
420gacgcctaga cggaggggcc ctactcagac cccatcgagc cagttcccaa gcttttccct
480ccgacctgct ccctcccggg gcgcgtgagg gtgcgggtcg ggggtgaacc tggtgttggg
540gaaagtgatt
550134550DNAHomo sapiens 134aatcactttc cccaacacca ggttcacccc cgacccgcac
cctcacgcgc cccgggaggg 60agcaggtcgg agggaaaagc ttgggaactg gctcgatggg
gtctgagtag ggcccctccg 120tctaggcgtc cgctcgccac tctcccgctg atggtgccga
caggagggcc gtgctccttg 180gcccttcctc tctccggctt gtcgccgccc gccgccccct
ctagagcgga gctcgacgcg 240ggtccggaat gccccgcgcg cgctcccgca gccgcgcttt
gtcccgtggg tgaccgccgg 300atgcctccaa gggctggcag agctgtccgc gtgcgacttt
cgctctggtt ggatttcccc 360ttccttcgca gccctgccgg gtagggtatt cctctttcct
ggaagactgg tggggggtgg 420aggggagttg ggggggctcc attgagagaa cgctccctcg
ccccaagggt tgggggagct 480tttcttcctt agccaaccct ccgttcccca gagctgctct
agtaattact gtggagatac 540cagttcccct
5501352800DNAHomo sapiens 135cgggcaaaaa tggagagcag
gcagaggtca catcctcctc ctcttcctca cgctcccggg 60ctgcgtgccc acaggggcac
agccctgtgc gcggtgccac cgggggccat caggctgggt 120tagaggaagg cccgacctcc
gcgcagcaaa gaaaacaaac acagatgtgt ttggctggga 180ccgggaggga gaaagtggcc
cccttccccc gcccgcgcgc tcccccgggc gtgaggctct 240ccgggcggcg cggggcgcgg
gcgaggctga cagtccccgg cggcccctcc tcccccacgg 300ggtgcgcgcc tggcccggcc
cagccccctc tccggggttt ccccgggtgc tctcctcgct 360ttctctttgt ctctgctgtt
ctttctcggg ctcccgggtt cccacccgcc tgtgctctcc 420ctctcgggcg tccgggccgg
ttccctttaa ctttcttctt tcccggggtg aaaactttgc 480tcggagctgg cggcagctcg
cggacgttat tggccggcgc cccgcccggc ggccccgccc 540cccgcccccg cgctcccctc
cgcccctcac tcccagcgcg agtggcggcg gcggcggagc 600cttcgggggc gagcgcgcgt
gtgtgtgagt gcgcgccggc cagcgtgagt gtgtgtgcgc 660cccgggcgcg ggcagggcag
cactccgagc tcggcgggag cggcgggagc cgggcggccg 720cgtagtcact cgggcgagag
aggcggcggc ggggccggga ccggggctgg ggctggggca 780gcggcggccg cgccgggcat
ggagctggca agcccgcgct gaggcgggac gcgcctgcta 840gcagcgagcg agaggctctc
cggcgaccgg cgcgcgggct ccccggaggg gccaggcaaa 900cttttctttc tcttttgccc
cctccagagg taaagtcccg aacgcggact ttccggcggg 960gacgcgatcg gggggcatct
gagagggacc ccgggctgcg agacgaaggg gcgcgggccg 1020tgcagagtcg gggtccccca
gctctcctgc gcccgaaact tggggtgcga ggggggctgg 1080tcgcggacgg ggagaccggc
tcaggcatgc ccctcgggcg gcgtgggggc ggcggtggcg 1140gggaagcaga gcgttctccc
gccgggcggg gaagaagggg cgcgagcggt gcggacttgg 1200agggccccgg cttcgccgcc
cgcgggactt tgggggagag aggcgggcag tcggctgcgg 1260ggtgggtgcc caggaagccg
ggcgttctcc cgcatctccg ctcgccaccc cgccgagagc 1320tggagggcgc ggggcgggct
ggctgagcgc agctcccttc tctccgcagg cgccttctgc 1380ggcaggcgga cagatcctcg
gcgcggcagg gccggggcaa gctggacgca gcatgatgcg 1440cgcagtgtgg gaggcgctgg
cggcgctggc ggcggtggcg tgcctggtgg gcgcggtgcg 1500cggcgggccc gggctcagca
tgttcgcggg ccaggcggcg cagcccgatc cctgctcgga 1560cgagaacggc cacccgcgcc
gctgcatccc ggactttgtc aatgcggcct tcggcaagga 1620cgtgcgcgtg tccagcacct
gcggccggcc cccggcgcgc tactgcgtgg tgagcgagcg 1680cggcgaggag cggctgcgct
cgtgccacct ctgcaacgcg tccgacccca agaaggcgca 1740cccgcccgcc ttcctcaccg
acctcaacaa cccgcacaac ctgacgtgct ggcagtccga 1800gaactacctg cagttcccgc
acaacgtcac gctcacactg tccctcggca agaagttcga 1860agtgacctac gtgagcctgc
agttctgctc gccgcggccc gagtccatgg ccatctacaa 1920gtccatggac tacgggcgca
cgtgggtgcc cttccagttc tactccacgc agtgccgcaa 1980gatgtacaac cggccgcacc
gcgcgcccat caccaagcag aacgagcagg aggccgtgtg 2040caccgactcg cacaccgaca
tgcgcccgct ctcgggcggc ctcatcgcct tcagcacgct 2100ggacgggcgg ccctcggcgc
acgacttcga caactcgccc gtgctgcagg actgggtcac 2160ggccacagac atccgcgtgg
ccttcagccg cctgcacacg ttcggcgacg agaacgagga 2220cgactcggag ctggcgcgcg
actcgtactt ctacgcggtg tccgacctgc aggtgggcgg 2280ccggtgcaag tgcaacggcc
acgcggcccg ctgcgtgcgc gaccgcgacg acagcctggt 2340gtgcgactgc aggcacaaca
cggccggccc ggagtgcgac cgctgcaagc ccttccacta 2400cgaccggccc tggcagcgcg
ccacagcccg cgaagccaac gagtgcgtgg gtgagtgggg 2460tgcggcggcg gagccggcgg
cgggtggggc cgcgggcggg agctgctggg cctcgcagcg 2520gcgagttcat aggagcgcgg
gtcgagggaa cggcgggagg cgcgttcgcc gatgcccggg 2580acccgggagg gctcagagca
ggtccactcg ctcgcgtggc gctcgtggtg gacgcccgaa 2640tttgcgccca gtgctctctg
cgaagccaag aagcagcagg agaaatgttc ccgggagggg 2700gtttggcaga acatttgcag
ataggtctcc gctaaccctg gatccaaacg caaacattca 2760ttgccttccc cctcgttggg
ttggacgctg ggattcacct 28001362800DNAHomo sapiens
136aggtgaatcc cagcgtccaa cccaacgagg gggaaggcaa tgaatgtttg cgtttggatc
60cagggttagc ggagacctat ctgcaaatgt tctgccaaac cccctcccgg gaacatttct
120cctgctgctt cttggcttcg cagagagcac tgggcgcaaa ttcgggcgtc caccacgagc
180gccacgcgag cgagtggacc tgctctgagc cctcccgggt cccgggcatc ggcgaacgcg
240cctcccgccg ttccctcgac ccgcgctcct atgaactcgc cgctgcgagg cccagcagct
300cccgcccgcg gccccacccg ccgccggctc cgccgccgca ccccactcac ccacgcactc
360gttggcttcg cgggctgtgg cgcgctgcca gggccggtcg tagtggaagg gcttgcagcg
420gtcgcactcc gggccggccg tgttgtgcct gcagtcgcac accaggctgt cgtcgcggtc
480gcgcacgcag cgggccgcgt ggccgttgca cttgcaccgg ccgcccacct gcaggtcgga
540caccgcgtag aagtacgagt cgcgcgccag ctccgagtcg tcctcgttct cgtcgccgaa
600cgtgtgcagg cggctgaagg ccacgcggat gtctgtggcc gtgacccagt cctgcagcac
660gggcgagttg tcgaagtcgt gcgccgaggg ccgcccgtcc agcgtgctga aggcgatgag
720gccgcccgag agcgggcgca tgtcggtgtg cgagtcggtg cacacggcct cctgctcgtt
780ctgcttggtg atgggcgcgc ggtgcggccg gttgtacatc ttgcggcact gcgtggagta
840gaactggaag ggcacccacg tgcgcccgta gtccatggac ttgtagatgg ccatggactc
900gggccgcggc gagcagaact gcaggctcac gtaggtcact tcgaacttct tgccgaggga
960cagtgtgagc gtgacgttgt gcgggaactg caggtagttc tcggactgcc agcacgtcag
1020gttgtgcggg ttgttgaggt cggtgaggaa ggcgggcggg tgcgccttct tggggtcgga
1080cgcgttgcag aggtggcacg agcgcagccg ctcctcgccg cgctcgctca ccacgcagta
1140gcgcgccggg ggccggccgc aggtgctgga cacgcgcacg tccttgccga aggccgcatt
1200gacaaagtcc gggatgcagc ggcgcgggtg gccgttctcg tccgagcagg gatcgggctg
1260cgccgcctgg cccgcgaaca tgctgagccc gggcccgccg cgcaccgcgc ccaccaggca
1320cgccaccgcc gccagcgccg ccagcgcctc ccacactgcg cgcatcatgc tgcgtccagc
1380ttgccccggc cctgccgcgc cgaggatctg tccgcctgcc gcagaaggcg cctgcggaga
1440gaagggagct gcgctcagcc agcccgcccc gcgccctcca gctctcggcg gggtggcgag
1500cggagatgcg ggagaacgcc cggcttcctg ggcacccacc ccgcagccga ctgcccgcct
1560ctctccccca aagtcccgcg ggcggcgaag ccggggccct ccaagtccgc accgctcgcg
1620ccccttcttc cccgcccggc gggagaacgc tctgcttccc cgccaccgcc gcccccacgc
1680cgcccgaggg gcatgcctga gccggtctcc ccgtccgcga ccagcccccc tcgcacccca
1740agtttcgggc gcaggagagc tgggggaccc cgactctgca cggcccgcgc cccttcgtct
1800cgcagcccgg ggtccctctc agatgccccc cgatcgcgtc cccgccggaa agtccgcgtt
1860cgggacttta cctctggagg gggcaaaaga gaaagaaaag tttgcctggc ccctccgggg
1920agcccgcgcg ccggtcgccg gagagcctct cgctcgctgc tagcaggcgc gtcccgcctc
1980agcgcgggct tgccagctcc atgcccggcg cggccgccgc tgccccagcc ccagccccgg
2040tcccggcccc gccgccgcct ctctcgcccg agtgactacg cggccgcccg gctcccgccg
2100ctcccgccga gctcggagtg ctgccctgcc cgcgcccggg gcgcacacac actcacgctg
2160gccggcgcgc actcacacac acgcgcgctc gcccccgaag gctccgccgc cgccgccact
2220cgcgctggga gtgaggggcg gaggggagcg cgggggcggg gggcggggcc gccgggcggg
2280gcgccggcca ataacgtccg cgagctgccg ccagctccga gcaaagtttt caccccggga
2340aagaagaaag ttaaagggaa ccggcccgga cgcccgagag ggagagcaca ggcgggtggg
2400aacccgggag cccgagaaag aacagcagag acaaagagaa agcgaggaga gcacccgggg
2460aaaccccgga gagggggctg ggccgggcca ggcgcgcacc ccgtggggga ggaggggccg
2520ccggggactg tcagcctcgc ccgcgccccg cgccgcccgg agagcctcac gcccggggga
2580gcgcgcgggc gggggaaggg ggccactttc tccctcccgg tcccagccaa acacatctgt
2640gtttgttttc tttgctgcgc ggaggtcggg ccttcctcta acccagcctg atggcccccg
2700gtggcaccgc gcacagggct gtgcccctgt gggcacgcag cccgggagcg tgaggaagag
2760gaggaggatg tgacctctgc ctgctctcca tttttgcccg
28001371300DNAHomo sapiens 137gcagtcctgt gtgactggtg agactcttgt aggggcgttt
ctacaacgac gaaacccttc 60ctaggcactc actccaacag aataacaagc ccattttatt
agtatttcgt tttccatgta 120aagttctgct catacgaata tatttataat tctgattttt
ttacggcatt ggggagcaca 180ccgacaggct gctgaacggt ggctggagat tcgagggaaa
acgaagttcg ccgaggcggc 240ctcgggcggg caggtcccgg gctccatcac agggcacacg
cggctaccag ggacgcagcc 300ccccaacaca cacacacaca cacacacaca cacacacaca
cacacacaca ccctctccca 360ctcatgcctg gcaacccagc agaaacttcg gactggggca
aaacaagccc gggccccggc 420ggcacgcggg gctaggcgcg ttcccgccag tacctggtcg
cgaggccgct cgcggggtgc 480cctgcgtgcc ccccactccc gcagcccgcg ccctgctcgc
tcactgtggg ggcgcagcgg 540ccaggcttct ctgtttgttg tttaaagaaa tcctagggcg
ggcgagcggc ggcatctagg 600ggagggggcg cagccagaat tcccttccag caagcgcgtg
aggggcattc tcaacgcaaa 660accagaccca gaaagtagtg accagccctc ctcggattac
ccttcattgg ctcctccctt 720gctcccccca ccctccagat ttgcataaaa aaggccaaga
aaactctggc tgtgccccag 780caacggctca ttctgctccc ccgggtcgga gccccccgga
gctgcgcgcg ggcttgcagc 840gcctcgcccg cgctgtcctc ccggtgtccc gcttctccgc
gccccagccg ccggctgcca 900gcttttcggg gccccgagtc gcacccagcg aagagagcgg
gcccgggaca agctcgaact 960ccggccgcct cgcccttccc cggctccgct ccctctgccc
cctcggggtc gcgcgcccac 1020gatgctgcag ggccctggct cgctgctgct gctcttcctc
gcctcgcact gctgcctggg 1080ctcggcgcgc gggctcttcc tctttggcca gcccgacttc
tcctacaagc gcagcaattg 1140caagcccatc cctgccaacc tgcagctgtg ccacggcatc
gaataccaga acatgcggct 1200gcccaacctg ctgggccacg agaccatgaa ggaggtgctg
gagcaggccg gcgcttggat 1260cccgctggtc atgaagcagt gccacccgga caccaagaag
13001381300DNAHomo sapiens 138cttcttggtg tccgggtggc
actgcttcat gaccagcggg atccaagcgc cggcctgctc 60cagcacctcc ttcatggtct
cgtggcccag caggttgggc agccgcatgt tctggtattc 120gatgccgtgg cacagctgca
ggttggcagg gatgggcttg caattgctgc gcttgtagga 180gaagtcgggc tggccaaaga
ggaagagccc gcgcgccgag cccaggcagc agtgcgaggc 240gaggaagagc agcagcagcg
agccagggcc ctgcagcatc gtgggcgcgc gaccccgagg 300gggcagaggg agcggagccg
gggaagggcg aggcggccgg agttcgagct tgtcccgggc 360ccgctctctt cgctgggtgc
gactcggggc cccgaaaagc tggcagccgg cggctggggc 420gcggagaagc gggacaccgg
gaggacagcg cgggcgaggc gctgcaagcc cgcgcgcagc 480tccggggggc tccgacccgg
gggagcagaa tgagccgttg ctggggcaca gccagagttt 540tcttggcctt ttttatgcaa
atctggaggg tggggggagc aagggaggag ccaatgaagg 600gtaatccgag gagggctggt
cactactttc tgggtctggt tttgcgttga gaatgcccct 660cacgcgcttg ctggaaggga
attctggctg cgccccctcc cctagatgcc gccgctcgcc 720cgccctagga tttctttaaa
caacaaacag agaagcctgg ccgctgcgcc cccacagtga 780gcgagcaggg cgcgggctgc
gggagtgggg ggcacgcagg gcaccccgcg agcggcctcg 840cgaccaggta ctggcgggaa
cgcgcctagc cccgcgtgcc gccggggccc gggcttgttt 900tgccccagtc cgaagtttct
gctgggttgc caggcatgag tgggagaggg tgtgtgtgtg 960tgtgtgtgtg tgtgtgtgtg
tgtgtgtgtg tgtgttgggg ggctgcgtcc ctggtagccg 1020cgtgtgccct gtgatggagc
ccgggacctg cccgcccgag gccgcctcgg cgaacttcgt 1080tttccctcga atctccagcc
accgttcagc agcctgtcgg tgtgctcccc aatgccgtaa 1140aaaaatcaga attataaata
tattcgtatg agcagaactt tacatggaaa acgaaatact 1200aataaaatgg gcttgttatt
ctgttggagt gagtgcctag gaagggtttc gtcgttgtag 1260aaacgcccct acaagagtct
caccagtcac acaggactgc 13001391034DNAHomo sapiens
139gctgcctttg ttctttgact actcagccaa ttcaggtctg agctgttctt cgacgccgcc
60ctagatgcga tgatgaaggt caggtgcccg catcccaccc accgtcccct cgcaggggcc
120ctaggaccca cccagatccc gcctgtctct ctccccgcgg caggttccgc tgcatcgtgc
180accctttccg cgagaagctg accctgcgga aggcgctcgt caccatcgcc gtcatctggg
240ccctggcgct gctcatcatg tgtccctcgg ccgtcacgct gaccgtcacc cgtgaggagc
300accacttcat ggtggacgcc cgcaaccgct cctacccgct ctactcctgc tgggaggcct
360ggcccgagaa gggcatgcgc agggtctaca ccactgtgct cttctcgcac atctacctgg
420cgccgctggc gctcatcgtg gtcatgtacg cccgcatcgc gcgcaagctc tgccaggccc
480cgggcccggc ccccgggggc gaggaggctg cggacccgcg agcatcgcgg cgcagagcgc
540gcgtggtgca catgctggtc atggtggcgc tgttcttcac gctgtcctgg ctgccgctct
600gggcgctgct gctgctcatc gactacgggc agctcagcgc gccgcagctg cacctggtca
660ccgtctacgc cttccccttc gcgcactggc tggccttctt caacagcagc gccaacccca
720tcatctacgg ctacttcaac gagaacttcc gccgcggctt ccaggccgcc ttccgcgccc
780gcctctgccc gcgcccgtcg gggagccaca aggaggccta ctccgagcgg cccggcgggc
840ttctgcacag gcgggtcttc gtggtggtgc ggcccagcga ctccgggctg ccctctgagt
900cgggccctag cagtggggcc cccaggcccg gccgcctccc gctgcggaat gggcgggtgg
960ctcaccacgg cttgcccagg gaagggcctg gctgctccca cctgcccctc accattccag
1020cctgggatat ctga
10341401034DNAHomo sapiens 140tcagatatcc caggctggaa tggtgagggg caggtgggag
cagccaggcc cttccctggg 60caagccgtgg tgagccaccc gcccattccg cagcgggagg
cggccgggcc tgggggcccc 120actgctaggg cccgactcag agggcagccc ggagtcgctg
ggccgcacca ccacgaagac 180ccgcctgtgc agaagcccgc cgggccgctc ggagtaggcc
tccttgtggc tccccgacgg 240gcgcgggcag aggcgggcgc ggaaggcggc ctggaagccg
cggcggaagt tctcgttgaa 300gtagccgtag atgatggggt tggcgctgct gttgaagaag
gccagccagt gcgcgaaggg 360gaaggcgtag acggtgacca ggtgcagctg cggcgcgctg
agctgcccgt agtcgatgag 420cagcagcagc gcccagagcg gcagccagga cagcgtgaag
aacagcgcca ccatgaccag 480catgtgcacc acgcgcgctc tgcgccgcga tgctcgcggg
tccgcagcct cctcgccccc 540gggggccggg cccggggcct ggcagagctt gcgcgcgatg
cgggcgtaca tgaccacgat 600gagcgccagc ggcgccaggt agatgtgcga gaagagcaca
gtggtgtaga ccctgcgcat 660gcccttctcg ggccaggcct cccagcagga gtagagcggg
taggagcggt tgcgggcgtc 720caccatgaag tggtgctcct cacgggtgac ggtcagcgtg
acggccgagg gacacatgat 780gagcagcgcc agggcccaga tgacggcgat ggtgacgagc
gccttccgca gggtcagctt 840ctcgcggaaa gggtgcacga tgcagcggaa cctgccgcgg
ggagagagac aggcgggatc 900tgggtgggtc ctagggcccc tgcgagggga cggtgggtgg
gatgcgggca cctgaccttc 960atcatcgcat ctagggcggc gtcgaagaac agctcagacc
tgaattggct gagtagtcaa 1020agaacaaagg cagc
1034141800DNAHomo sapiens 141agaaaggtaa tatttggagg
cctccgaggg acgggcaggg gaaagaggga tcctctgacc 60cagcgggggc tgggaggatg
gctgtttttg ttttttccca cctagcctcg gaatcgcgga 120ctgcgcccag tgacggactc
aaacttaccc ttccctctga ccccgccgta ggatgacgcc 180tcaaccctcg ggtgcgccca
ctgtccaagt gacccgtgag acggagcggt ccttccccag 240agcctcggaa gacgaagtga
cctgccccac gtccgccccg cccagcccca ctcgcacacg 300ggggaactgc gcagaggcgg
aagagggagg ctgccgaggg gccccgagga agctccgggc 360acggcgcggg ggacgcagcc
ggcctaagag cgagttggca ctgagcaagc agcgacggag 420tcggcgaaag aaggccaacg
accgcgagcg caatcgaatg cacaacctca actcggcact 480ggacgccctg cgcggtgtcc
tgcccacctt cccagacgac gcgaagctca ccaagatcga 540gacgctgcgc ttcgcccaca
actacatctg ggcgctgact caaacgctgc gcatagcgga 600ccacagcttg tacgcgctgg
agccgccggc gccgcactgc ggggagctgg gcagcccagg 660cggttccccc ggggactggg
ggtccctcta ctccccagtc tcccaggctg gcagcctgag 720tcccgccgcg tcgctggagg
agcgacccgg gctgctgggg gccacctttt ccgcctgctt 780gagcccaggc agtctggctt
800142800DNAHomo sapiens
142aagccagact gcctgggctc aagcaggcgg aaaaggtggc ccccagcagc ccgggtcgct
60cctccagcga cgcggcggga ctcaggctgc cagcctggga gactggggag tagagggacc
120cccagtcccc gggggaaccg cctgggctgc ccagctcccc gcagtgcggc gccggcggct
180ccagcgcgta caagctgtgg tccgctatgc gcagcgtttg agtcagcgcc cagatgtagt
240tgtgggcgaa gcgcagcgtc tcgatcttgg tgagcttcgc gtcgtctggg aaggtgggca
300ggacaccgcg cagggcgtcc agtgccgagt tgaggttgtg cattcgattg cgctcgcggt
360cgttggcctt ctttcgccga ctccgtcgct gcttgctcag tgccaactcg ctcttaggcc
420ggctgcgtcc cccgcgccgt gcccggagct tcctcggggc ccctcggcag cctccctctt
480ccgcctctgc gcagttcccc cgtgtgcgag tggggctggg cggggcggac gtggggcagg
540tcacttcgtc ttccgaggct ctggggaagg accgctccgt ctcacgggtc acttggacag
600tgggcgcacc cgagggttga ggcgtcatcc tacggcgggg tcagagggaa gggtaagttt
660gagtccgtca ctgggcgcag tccgcgattc cgaggctagg tgggaaaaaa caaaaacagc
720catcctccca gcccccgctg ggtcagagga tccctctttc ccctgcccgt ccctcggagg
780cctccaaata ttacctttct
8001431550DNAHomo sapiens 143taaagcttcc ccagagggag gaaaggtggg ggcggggcgg
ctgctgaggc ccaggatata 60agggctggag gtgctgcttt caggcctggc cagcccacca
tgcacgccca ctgcctgccc 120ttccttctgc acgcctggtg ggccctactc caggcgggtg
ctgcgacggt ggccactgcg 180ctcctgcgta cgcgggggca gccctcgtcg ccatcccctc
tggcgtacat gctgagcctc 240taccgcgacc cgctgccgag ggcagacatc atccgcagcc
tacaggcaga aggtaggcag 300tgccgcgtgc cgcgccctgc tgggcacccc cggggcgcct
ccgccgcgtc cagccagcgg 360actcgggaag tgctgtgggt tgggggctgc ggctccgagc
cgggtttgca gccgcccggg 420cgtcccgagc ccagggccta gctctgcggg tgtctccgcg
tcagcaggct cggggtgcag 480cgttggtggc tgggggcgta tccacggccg agtcgggaag
ggattctagc gttcagggtg 540tgtcctcgac ggggaccatt gtctctgggt tttggtttgg
gattgcgcgg agcgcagcgc 600ggaagggtgg gagcttctaa tctccagtct tgtgaagttg
cttatcccgg agcctgggtc 660tgcgcatctg taggataggt gtaataaata acacctcgcc
tatcagactg tggaaagcgc 720gagatgacaa tgcgcgcgaa acgctcagcg cagtacccgg
cacagccaca gtcaacggtc 780gttggtatta ctgtaatggt ttggtcttgg cgattttttt
ttctttctgc gagtgagggt 840gaatgggtcc cggggtgtga cgtcgggagt atcggcagct
gagctggtaa catcggggat 900tcgggctcac ggcccggaga tcagggatgg gctgtcccga
agtcgcgaac tgtggcagcc 960ttgggtcctc cagccgcgcc ggggaagtgt caagtgtctc
gcttaacccc gggttcgggg 1020ccatgatttg caggggagtg ggtgtcaagg acggcaggga
tctgagggta tcgccctcga 1080ggacctggca gcgcgttctg ggcacccagc gcggcgagca
ggtgggtgct gcggagaggg 1140agccccttcc gcgcctcaat ccacattctg ccgcctgggc
agccgcggcc gcccacgcct 1200ccctccgcct gcgggggcca gacggccctc cctggggccg
gggcgcaatc cacaaacgct 1260aatctgatcc gacctgccgc ctgcccgccc cttgtgacct
ggtgccgggg gcccttcgct 1320cccgcgcctg gggtcagaca gccggtgacc ctctccggaa
gggtcatctg gggaccagcc 1380agaccagggg acaccctcgg gggcggggca atgagaaatt
tgctggagtg ctcggcccct 1440caaccgaaaa gcggccgggg atgggagggg gcaaagaagg
gagggagcgc ttttccagtt 1500cactcccttc tggaaagttc gagatgtgtg cggtgatgga
caggcatctg 15501441550DNAHomo sapiens 144cagatgcctg
tccatcaccg cacacatctc gaactttcca gaagggagtg aactggaaaa 60gcgctccctc
ccttctttgc cccctcccat ccccggccgc ttttcggttg aggggccgag 120cactccagca
aatttctcat tgccccgccc ccgagggtgt cccctggtct ggctggtccc 180cagatgaccc
ttccggagag ggtcaccggc tgtctgaccc caggcgcggg agcgaagggc 240ccccggcacc
aggtcacaag gggcgggcag gcggcaggtc ggatcagatt agcgtttgtg 300gattgcgccc
cggccccagg gagggccgtc tggcccccgc aggcggaggg aggcgtgggc 360ggccgcggct
gcccaggcgg cagaatgtgg attgaggcgc ggaaggggct ccctctccgc 420agcacccacc
tgctcgccgc gctgggtgcc cagaacgcgc tgccaggtcc tcgagggcga 480taccctcaga
tccctgccgt ccttgacacc cactcccctg caaatcatgg ccccgaaccc 540ggggttaagc
gagacacttg acacttcccc ggcgcggctg gaggacccaa ggctgccaca 600gttcgcgact
tcgggacagc ccatccctga tctccgggcc gtgagcccga atccccgatg 660ttaccagctc
agctgccgat actcccgacg tcacaccccg ggacccattc accctcactc 720gcagaaagaa
aaaaaaatcg ccaagaccaa accattacag taataccaac gaccgttgac 780tgtggctgtg
ccgggtactg cgctgagcgt ttcgcgcgca ttgtcatctc gcgctttcca 840cagtctgata
ggcgaggtgt tatttattac acctatccta cagatgcgca gacccaggct 900ccgggataag
caacttcaca agactggaga ttagaagctc ccacccttcc gcgctgcgct 960ccgcgcaatc
ccaaaccaaa acccagagac aatggtcccc gtcgaggaca caccctgaac 1020gctagaatcc
cttcccgact cggccgtgga tacgccccca gccaccaacg ctgcaccccg 1080agcctgctga
cgcggagaca cccgcagagc taggccctgg gctcgggacg cccgggcggc 1140tgcaaacccg
gctcggagcc gcagccccca acccacagca cttcccgagt ccgctggctg 1200gacgcggcgg
aggcgccccg ggggtgccca gcagggcgcg gcacgcggca ctgcctacct 1260tctgcctgta
ggctgcggat gatgtctgcc ctcggcagcg ggtcgcggta gaggctcagc 1320atgtacgcca
gaggggatgg cgacgagggc tgcccccgcg tacgcaggag cgcagtggcc 1380accgtcgcag
cacccgcctg gagtagggcc caccaggcgt gcagaaggaa gggcaggcag 1440tgggcgtgca
tggtgggctg gccaggcctg aaagcagcac ctccagccct tatatcctgg 1500gcctcagcag
ccgccccgcc cccacctttc ctccctctgg ggaagcttta
15501451050DNAHomo sapiens 145accccggggc gtgggagaag cccctgcttg gggggaccgt
ctgctgttta ggggctcccc 60ttcgacacgt gggaggcaaa agtgcagagc gcaccatcat
ccagctccgg ccgcactgca 120cagcgaggcc ggcccggagc ccggatgctg ggctcggtcc
cgccgaggct cggcctggct 180gtaaagcaga ggggggcgag ggaagccggg ccagcgggtg
tcgcgggtag ccggcgtccg 240ggacggggtg tggcgcccag agcgctgctg cctctcgcag
ccaggaggct ggatgtcggg 300tttgggtgtc ttccagaagg agccgcacta gcgacgaggg
aagaggaact ggcttcccgg 360gcagtctccc ccgccccaaa cttttcctcc tcgcggaggg
tgggcgggcg gagggaggaa 420gcgcagccgg ggaacgtggc gcccgcgttc ctcccgcccg
ggggctgcgg ctgggctgag 480tgtgtcttta aatctgagcc ccccgcccct cgcggtgggg
ccgggactcg cggtccgggc 540gggggcgggc gcggtgattg gcggccgggt cgggtccgcc
cctcggcgtt gggtagcggg 600gcgctgggga gcagcgcggc gcgcacgggc cggggcgcgc
aggtcccgtc gccggtgagc 660acgggctccc tctcgcgtgg cctcgccggg tccgcctggc
ctgcccacct ccggagccac 720ctctgccccc gcatgggctg gcgaagttgg gaggagcgag
ctggagccag agcgcgcgcc 780gggcgcgccc cgtcgctgcc tgactcggcg cccgcagttc
gggcgcagca cgccggccgc 840aggagcacgg atgccccccg gagccgcggg ctggcaggta
ccgaagtgtc ctgccctggg 900gctggcgagg ggagggcaaa tctggaatcc cccgggcacc
ccccagcccg aggctgctcc 960agacaccaac tccccatcct ttggagaggt gaggtcctgg
gccttcaccc cacacccgct 1020caggattggt ccctgggagg caagagggac
10501461050DNAHomo sapiens 146gtccctcttg cctcccaggg
accaatcctg agcgggtgtg gggtgaaggc ccaggacctc 60acctctccaa aggatgggga
gttggtgtct ggagcagcct cgggctgggg ggtgcccggg 120ggattccaga tttgccctcc
cctcgccagc cccagggcag gacacttcgg tacctgccag 180cccgcggctc cggggggcat
ccgtgctcct gcggccggcg tgctgcgccc gaactgcggg 240cgccgagtca ggcagcgacg
gggcgcgccc ggcgcgcgct ctggctccag ctcgctcctc 300ccaacttcgc cagcccatgc
gggggcagag gtggctccgg aggtgggcag gccaggcgga 360cccggcgagg ccacgcgaga
gggagcccgt gctcaccggc gacgggacct gcgcgccccg 420gcccgtgcgc gccgcgctgc
tccccagcgc cccgctaccc aacgccgagg ggcggacccg 480acccggccgc caatcaccgc
gcccgccccc gcccggaccg cgagtcccgg ccccaccgcg 540aggggcgggg ggctcagatt
taaagacaca ctcagcccag ccgcagcccc cgggcgggag 600gaacgcgggc gccacgttcc
ccggctgcgc ttcctccctc cgcccgccca ccctccgcga 660ggaggaaaag tttggggcgg
gggagactgc ccgggaagcc agttcctctt ccctcgtcgc 720tagtgcggct ccttctggaa
gacacccaaa cccgacatcc agcctcctgg ctgcgagagg 780cagcagcgct ctgggcgcca
caccccgtcc cggacgccgg ctacccgcga cacccgctgg 840cccggcttcc ctcgcccccc
tctgctttac agccaggccg agcctcggcg ggaccgagcc 900cagcatccgg gctccgggcc
ggcctcgctg tgcagtgcgg ccggagctgg atgatggtgc 960gctctgcact tttgcctccc
acgtgtcgaa ggggagcccc taaacagcag acggtccccc 1020caagcagggg cttctcccac
gccccggggt 1050147550DNAHomo sapiens
147ccgaaaggac ccgtcccagc gagccagggc ctggttttcc ttccgcagaa ggcggaggga
60ccggagcggg cgcgggcacc cctgggctct gaggggcgcg ctctgaaggg cggcggactt
120cagggccatg ctggctgtcc ccagaaagca ggagcccgaa accgcggggc caacgaacgc
180ccacattctc tgctacaacc tcgccactcc cctgcgcctc tccccttgcc ccctgccccc
240acaggtaacg cccagaacga gtgcttctcc cggtggggta ctgaggagcc tgggctgcag
300ctgccgagcc gccacagcca cgctgagccc ggcctggcct gcacactggc gccaccgcct
360ggcggggagc gggactgacg cgctcctctc cctctcctcc agcccagatc acggaggcgc
420ggagctccat ctcctgccct gggcgagggg agtgagggag acaaagactt tgggcacaac
480acccaccaca tagaacctat tctctagttg ggaaacaagt caaggcaaag gcgcacagag
540tgaaagtcag
550148550DNAHomo sapiens 148ctgactttca ctctgtgcgc ctttgccttg acttgtttcc
caactagaga ataggttcta 60tgtggtgggt gttgtgccca aagtctttgt ctccctcact
cccctcgccc agggcaggag 120atggagctcc gcgcctccgt gatctgggct ggaggagagg
gagaggagcg cgtcagtccc 180gctccccgcc aggcggtggc gccagtgtgc aggccaggcc
gggctcagcg tggctgtggc 240ggctcggcag ctgcagccca ggctcctcag taccccaccg
ggagaagcac tcgttctggg 300cgttacctgt gggggcaggg ggcaagggga gaggcgcagg
ggagtggcga ggttgtagca 360gagaatgtgg gcgttcgttg gccccgcggt ttcgggctcc
tgctttctgg ggacagccag 420catggccctg aagtccgccg cccttcagag cgcgcccctc
agagcccagg ggtgcccgcg 480cccgctccgg tccctccgcc ttctgcggaa ggaaaaccag
gccctggctc gctgggacgg 540gtcctttcgg
5501491550DNAHomo sapiens 149ccctccagtt tgctggagtt
gccggattac attgttcctc cccggtgtgc ggcgtgagct 60tcccccaccc gagcgcccaa
caagtctcct ttctccagcc tgcgcgctgc tgcgctgagg 120ccgaatgaag cgcagcacgg
tgcgggcagc ccgaggcccc gaggctgggc tctgtctgtc 180tgggactgcg ccgtgcccag
cctcggtccc ctctctgtgg gtaaggatgg ttgagtccag 240cctccacggc agcggctcct
tgtgccacta gcagcccttc ttctgcgctc tccgcctttt 300ctctctagac tggatctctc
ctcccccccg cgcccccctc cccgcatctc ccactcgctg 360gctctctctc cagctgcctc
ctctccaggt ctctcctggc tgcgcgcgct cctctccccg 420cttctccccc tcccgcagcc
tcgccgcctt ggtgccttcc tgcccggctc ggccggcgct 480cgtccccggc cccggccccg
ccagcccggg tctccgcgct cggagcagct cagccctgca 540gtggctcggg acccgatgct
atgagaggga agcgagccgg gcgcccagac cttcaggagg 600cgtcggatgc gcggcgggtc
ttgggaccgg gctctctctc cggctcgcct tgccctcggg 660tgattatttg gctccgctca
tagccctgcc ttcctcggag gagccatcgg tgtcgcgtgc 720gtgtggagta tctgcagaca
tgactgcgtg gaggagattc cagtcgctgc tcctgcttct 780cgggctgctg gtgctgtgcg
cgaggctcct cactgcagcg aagggtaaga cggacttgct 840cctggccggg gaggcggtag
agccctcgga ggccccgtgt gcggacgcga gtgtgcgttt 900tggggaccgc agggtacgga
gtggccgcct ctgcccggcg ctgctccatc gccgaagctc 960ggggaacgcg atgcacggga
gggagcttcc atcgcgctct ccccagccct cctgggcccc 1020cgccccaccc cgccattcct
tccccctctc ttgggctcac aggagagatc tctttttctc 1080ggcagtacag ggtgtcaagg
agaaaggaac ccaatacgag ttgggctgga actgtgctcc 1140gccggggcgg tgttgcctcc
tccgagacgt ggactccacg ggtcggggtg gctgaggggc 1200agttcccagg actttctccc
cggacccgac gcgcctggga aagcgtcccg ggtgaagccg 1260gcctggaaag ttcgggctct
ctacgggggt tttggtacca ataggcaaag gtctccgccg 1320gcccggcctc ctcgcaccca
tacaccccat tcctcctctc ctccttccct ctccaacgtc 1380ctcagccggc gaggagtagc
tgcctctaga aggtcgcccc cgctttcctc tcccccggac 1440ttcgctcctt gcaagttgta
aggtgttggc aaggtgcgtg aaacaggcta ggagttctgg 1500accggcttcc aagtcagata
cattcactgt gggcgcacgg gtatcctcct 15501501550DNAHomo sapiens
150aggaggatac ccgtgcgccc acagtgaatg tatctgactt ggaagccggt ccagaactcc
60tagcctgttt cacgcacctt gccaacacct tacaacttgc aaggagcgaa gtccggggga
120gaggaaagcg ggggcgacct tctagaggca gctactcctc gccggctgag gacgttggag
180agggaaggag gagaggagga atggggtgta tgggtgcgag gaggccgggc cggcggagac
240ctttgcctat tggtaccaaa acccccgtag agagcccgaa ctttccaggc cggcttcacc
300cgggacgctt tcccaggcgc gtcgggtccg gggagaaagt cctgggaact gcccctcagc
360caccccgacc cgtggagtcc acgtctcgga ggaggcaaca ccgccccggc ggagcacagt
420tccagcccaa ctcgtattgg gttcctttct ccttgacacc ctgtactgcc gagaaaaaga
480gatctctcct gtgagcccaa gagaggggga aggaatggcg gggtggggcg ggggcccagg
540agggctgggg agagcgcgat ggaagctccc tcccgtgcat cgcgttcccc gagcttcggc
600gatggagcag cgccgggcag aggcggccac tccgtaccct gcggtcccca aaacgcacac
660tcgcgtccgc acacggggcc tccgagggct ctaccgcctc cccggccagg agcaagtccg
720tcttaccctt cgctgcagtg aggagcctcg cgcacagcac cagcagcccg agaagcagga
780gcagcgactg gaatctcctc cacgcagtca tgtctgcaga tactccacac gcacgcgaca
840ccgatggctc ctccgaggaa ggcagggcta tgagcggagc caaataatca cccgagggca
900aggcgagccg gagagagagc ccggtcccaa gacccgccgc gcatccgacg cctcctgaag
960gtctgggcgc ccggctcgct tccctctcat agcatcgggt cccgagccac tgcagggctg
1020agctgctccg agcgcggaga cccgggctgg cggggccggg gccggggacg agcgccggcc
1080gagccgggca ggaaggcacc aaggcggcga ggctgcggga gggggagaag cggggagagg
1140agcgcgcgca gccaggagag acctggagag gaggcagctg gagagagagc cagcgagtgg
1200gagatgcggg gaggggggcg cgggggggag gagagatcca gtctagagag aaaaggcgga
1260gagcgcagaa gaagggctgc tagtggcaca aggagccgct gccgtggagg ctggactcaa
1320ccatccttac ccacagagag gggaccgagg ctgggcacgg cgcagtccca gacagacaga
1380gcccagcctc ggggcctcgg gctgcccgca ccgtgctgcg cttcattcgg cctcagcgca
1440gcagcgcgca ggctggagaa aggagacttg ttgggcgctc gggtggggga agctcacgcc
1500gcacaccggg gaggaacaat gtaatccggc aactccagca aactggaggg
15501511050DNAHomo sapiens 151tcctccttga gcagggagac catcggggtg caacctggcc
ggggcgggga ggaggtgcag 60ggcattgcca gagcgggcct gtccatgggc aagggacagc
gacctcctgg gccaggacat 120gtgagagctg cgcaggcctg ggcccggcgt ggcggaggtg
cgcgagagcg gccagaagag 180ggcgccagag agccaggcgc ggcccgcgga ggagcccgcg
ccggccccta tacccagctc 240cgcgccgcgc ggacccaccg agcccgcgct cagacgcccc
agctccaccg agaggccgct 300cgggccgtgt ccttcctctt ctccaggtgc aggcagagcc
cccgagccat ggccagccct 360tccggcagct ccgaagccac tggcaagccc cgaggcaggg
atggccggcc caggagggag 420gaggacgacg tccctcccga agagaagagg ctggggctgt
agctggaggg gggaagcgca 480cagcccgagg actgcgagaa cggggaggac gcgccgcggc
caggcaggga ggagaccggc 540acccagacag gtggcgaccg cagaggagta agtgacgcgg
gcgctggggt ccgggggtgc 600cgggggcgcc ggtaggggcg gcgggaggct ccgtggccgg
ccccgggttg aagttggtat 660tttagcggca actccgaagg gcgcggagtg acagcgcgtg
acggcctccg agacgccagc 720tgccgcttct cggctgtgtg gctttgactt cctgattctc
ccacgacgtc gctggctggg 780agacccactg gactctgcgg ctggccaaaa agagaggggc
agccccgcgt cctgggggcc 840cctagcaggg gaagtggcgg gtgttgcgct gggcatcctg
tctggggcat ctgtctggga 900ccctgttggt gcctctcacc tggcgagggg ccagtggtgg
gggtaggggg gaagtccctg 960gcgccaggct tggccaagcc ctgcttggct ggactgcggg
ctggcggcgc tcacccagct 1020cctcacctgt cccgcatctt cctgtttttc
10501521050DNAHomo sapiens 152gaaaaacagg aagatgcggg
acaggtgagg agctgggtga gcgccgccag cccgcagtcc 60agccaagcag ggcttggcca
agcctggcgc cagggacttc ccccctaccc ccaccactgg 120cccctcgcca ggtgagaggc
accaacaggg tcccagacag atgccccaga caggatgccc 180agcgcaacac ccgccacttc
ccctgctagg ggcccccagg acgcggggct gcccctctct 240ttttggccag ccgcagagtc
cagtgggtct cccagccagc gacgtcgtgg gagaatcagg 300aagtcaaagc cacacagccg
agaagcggca gctggcgtct cggaggccgt cacgcgctgt 360cactccgcgc ccttcggagt
tgccgctaaa ataccaactt caacccgggg ccggccacgg 420agcctcccgc cgcccctacc
ggcgcccccg gcacccccgg accccagcgc ccgcgtcact 480tactcctctg cggtcgccac
ctgtctgggt gccggtctcc tccctgcctg gccgcggcgc 540gtcctccccg ttctcgcagt
cctcgggctg tgcgcttccc ccctccagct acagccccag 600cctcttctct tcgggaggga
cgtcgtcctc ctccctcctg ggccggccat ccctgcctcg 660gggcttgcca gtggcttcgg
agctgccgga agggctggcc atggctcggg ggctctgcct 720gcacctggag aagaggaagg
acacggcccg agcggcctct cggtggagct ggggcgtctg 780agcgcgggct cggtgggtcc
gcgcggcgcg gagctgggta taggggccgg cgcgggctcc 840tccgcgggcc gcgcctggct
ctctggcgcc ctcttctggc cgctctcgcg cacctccgcc 900acgccgggcc caggcctgcg
cagctctcac atgtcctggc ccaggaggtc gctgtccctt 960gcccatggac aggcccgctc
tggcaatgcc ctgcacctcc tccccgcccc ggccaggttg 1020caccccgatg gtctccctgc
tcaaggagga 10501531300DNAHomo sapiens
153cccagtaagt caccaattaa gtctttacta cttaaaagca aaatccacct atgtcctgaa
60cagtatccac tttacgagcc tcattatatg tacgagataa aattcagaaa taaataaata
120tacatgtata cgtatacaaa tatatttcaa attaaaaaat acttttagat agtggtatgt
180attacattta gaaattaata acgaagtaaa ttatgggatg tcatccacgc ctgtcccaaa
240ggtaccgaat ttataaatca tctcaggtgc ggagcaggac aggttgaaaa taggaatgac
300atgaacccgc gcggaacagc tgccggcgcg gtgtccaggg cggcaccccg cccggtcccg
360gcccctccag ccctgggccc gacccctact acgcctctgc ctcgacgcga acgcggagcc
420cgagcgcgcg tcacgccgtg tggggccgaa gaggctgcta cccagaggcg gagtgcgggc
480tcgcgagggt ccccacccga ctctcgctcc cgccagcacc tacggactcg cgtccccgcc
540gcgcgccgac tcgggagcag caccgccccc ggcacaggag cctcacgcgc ctcttaccta
600acaggaagtt gggtggaagc agcgcggacc cacggcacac cgaacgcact ccaacagaac
660ccgacgcaga cacgcgcttt caaccggcgg agacactggc agggccagaa acgcgcgcag
720cgggggcggg aggtcggtaa gctccccgcc cctgcccgag accccgcccc ggcccggccc
780cgcctttttc tctgcctccc ctccctgcac gtacgggccc cgcccctcgc gcgacgtttt
840ttgttgaccc ggaaacggat tctccggagc cgaggtccgc tcgggtgagt gccctccgct
900ttttgtggcc aaacccagcc acgcagttcc cttcctgcgg cgtcctccac acccggggtc
960tgctggtctc cgcggatgtc acaggctcgg caaccgccct cctgtcggcg gggagtcccg
1020cgacgcccgg aaatgctccg aagcctgtcg cccagctgcc agatctgcgt ctgtgtccgg
1080ttccgtcact gaggtcgccc ctgtccggcc cttccaccct agttctcttc accgtccgcc
1140catcctatcg cgcgcggcct caggtcccga ttcggcatgt ggcttgtctt ccatcgtccc
1200caccctcgcc cctcttggcc cctcagggca gccctgggat tcggcagacg ccagtcctcc
1260ctgagatgct tccccatcct tccctccgcc aggccctacg
13001541300DNAHomo sapiens 154cgtagggcct ggcggaggga aggatgggga agcatctcag
ggaggactgg cgtctgccga 60atcccagggc tgccctgagg ggccaagagg ggcgagggtg
gggacgatgg aagacaagcc 120acatgccgaa tcgggacctg aggccgcgcg cgataggatg
ggcggacggt gaagagaact 180agggtggaag ggccggacag gggcgacctc agtgacggaa
ccggacacag acgcagatct 240ggcagctggg cgacaggctt cggagcattt ccgggcgtcg
cgggactccc cgccgacagg 300agggcggttg ccgagcctgt gacatccgcg gagaccagca
gaccccgggt gtggaggacg 360ccgcaggaag ggaactgcgt ggctgggttt ggccacaaaa
agcggagggc actcacccga 420gcggacctcg gctccggaga atccgtttcc gggtcaacaa
aaaacgtcgc gcgaggggcg 480gggcccgtac gtgcagggag gggaggcaga gaaaaaggcg
gggccgggcc ggggcggggt 540ctcgggcagg ggcggggagc ttaccgacct cccgcccccg
ctgcgcgcgt ttctggccct 600gccagtgtct ccgccggttg aaagcgcgtg tctgcgtcgg
gttctgttgg agtgcgttcg 660gtgtgccgtg ggtccgcgct gcttccaccc aacttcctgt
taggtaagag gcgcgtgagg 720ctcctgtgcc gggggcggtg ctgctcccga gtcggcgcgc
ggcggggacg cgagtccgta 780ggtgctggcg ggagcgagag tcgggtgggg accctcgcga
gcccgcactc cgcctctggg 840tagcagcctc ttcggcccca cacggcgtga cgcgcgctcg
ggctccgcgt tcgcgtcgag 900gcagaggcgt agtaggggtc gggcccaggg ctggaggggc
cgggaccggg cggggtgccg 960ccctggacac cgcgccggca gctgttccgc gcgggttcat
gtcattccta ttttcaacct 1020gtcctgctcc gcacctgaga tgatttataa attcggtacc
tttgggacag gcgtggatga 1080catcccataa tttacttcgt tattaatttc taaatgtaat
acataccact atctaaaagt 1140attttttaat ttgaaatata tttgtatacg tatacatgta
tatttattta tttctgaatt 1200ttatctcgta catataatga ggctcgtaaa gtggatactg
ttcaggacat aggtggattt 1260tgcttttaag tagtaaagac ttaattggtg acttactggg
13001551300DNAHomo sapiens 155accggcgtcc cgctgggggc
gcgcgagccc cacccccaga gatgctgact cagcaagtcg 60ggaggggttg ggggtgggac
ctgccaatct gcatttccaa ccggcgccca ggtgacgctg 120actctgctgg tctaccgtct
tgggggtcac ctaatttttc agcgatgcct cccagctggg 180gaggccaaga agtgcctcgc
tcaaggtctt ccaacacccg acctccagac cctcaatcct 240gggccagcta caccgcaaac
ctttccagct gtctctcctg cgccctgcgt ttcttcccca 300cgtcacttgc cagggagccg
ctaaacagca agaccgcgcg ctctgcggct ccagagtgcg 360gatttcggtc gcgtgcggct
ctgaccgcgt cgccccatcc ctggcggggc cacgcacgga 420cgccatggct ggcgccgcgg
agccgggcga tgcgcgcgga ctctcccggg gccctgactg 480tccctgagtc ctccctgcgg
ggggcgtgcg cggcccgccc cccgcggcgc cacgcggccc 540ctcctcggcc ggggattggt
gcgccgggcg gggcggggcg gggcgggata aaggcgcggg 600gtctggctgc gcggggtctg
cgggcagctc caactctggg ttcgtagttt gcgctgggtg 660cgcaggaagg tcagtgtggg
ggtcgcccga catttccccc ccgcggaggt gggagccgag 720ccacatcttg gagtggggac
tggccgcgga gcgggttgcc cagggccggc cgaggtcggg 780gcgagccctg cgcggcgctg
gagactctgc attcccgggc gcgcgcaggg tccccggccg 840tggtcgcaga gtcaggaggg
gcggctccgg agcccggcgc ggggagggcc caggcgcagt 900cggggttggc agggcgcgac
actcgctccc ctccactttt gaaagggctt cccacgccga 960gaagaggggc gggcatggcc
ggcccggcga aaccggtttg tacagacttt gggaagccat 1020cgcctgcgga gggtgggacc
ccacagcttg tccacctgcc caggctgaga cctcgtgtcc 1080tagtcctgga tgccccacgg
gtttctcgtc ccgggcagcg gcgcacggga ggagaagact 1140cccggtctgc agtcagacct
ccctctgaga ccctccctag ctcaggctta gagctttggg 1200atttttctcg atcctttcta
gctttcagat catccccacg taaagttcag actttaccag 1260cccagagagt ttaaaaaaaa
aaaaagagag agagagaaag 13001561300DNAHomo sapiens
156ctttctctct ctctcttttt ttttttttaa actctctggg ctggtaaagt ctgaacttta
60cgtggggatg atctgaaagc tagaaaggat cgagaaaaat cccaaagctc taagcctgag
120ctagggaggg tctcagaggg aggtctgact gcagaccggg agtcttctcc tcccgtgcgc
180cgctgcccgg gacgagaaac ccgtggggca tccaggacta ggacacgagg tctcagcctg
240ggcaggtgga caagctgtgg ggtcccaccc tccgcaggcg atggcttccc aaagtctgta
300caaaccggtt tcgccgggcc ggccatgccc gcccctcttc tcggcgtggg aagccctttc
360aaaagtggag gggagcgagt gtcgcgccct gccaaccccg actgcgcctg ggccctcccc
420gcgccgggct ccggagccgc ccctcctgac tctgcgacca cggccgggga ccctgcgcgc
480gcccgggaat gcagagtctc cagcgccgcg cagggctcgc cccgacctcg gccggccctg
540ggcaacccgc tccgcggcca gtccccactc caagatgtgg ctcggctccc acctccgcgg
600gggggaaatg tcgggcgacc cccacactga ccttcctgcg cacccagcgc aaactacgaa
660cccagagttg gagctgcccg cagaccccgc gcagccagac cccgcgcctt tatcccgccc
720cgccccgccc cgcccggcgc accaatcccc ggccgaggag gggccgcgtg gcgccgcggg
780gggcgggccg cgcacgcccc ccgcagggag gactcaggga cagtcagggc cccgggagag
840tccgcgcgca tcgcccggct ccgcggcgcc agccatggcg tccgtgcgtg gccccgccag
900ggatggggcg acgcggtcag agccgcacgc gaccgaaatc cgcactctgg agccgcagag
960cgcgcggtct tgctgtttag cggctccctg gcaagtgacg tggggaagaa acgcagggcg
1020caggagagac agctggaaag gtttgcggtg tagctggccc aggattgagg gtctggaggt
1080cgggtgttgg aagaccttga gcgaggcact tcttggcctc cccagctggg aggcatcgct
1140gaaaaattag gtgaccccca agacggtaga ccagcagagt cagcgtcacc tgggcgccgg
1200ttggaaatgc agattggcag gtcccacccc caacccctcc cgacttgctg agtcagcatc
1260tctgggggtg gggctcgcgc gcccccagcg ggacgccggt
1300157800DNAHomo sapiens 157ctcatttcgg gccgcttttc tcagagggca aagatgggtc
agggtgggat gttacattag 60tgttgagact ctttggatcc gtttcgtggg taccgaggac
gcctgggtac gcgggacagg 120ctgcacccgc ctgctagagg cgccccatcg aggcgccacg
ggtgaagctc ccggccccac 180ctacggggcg gggctccggc tcggtccgac tattgcccgc
ggtgggggag ggggatggat 240cacgccacgc gccaaaggcg atcgcgactc tccttctgca
ggtagcctgg aaggctctct 300ctctttctct acgccaccct tttcgtggca ctgaaaagcc
ccgtcctctc ctcccagtcc 360cgcctcctcc gagcgttccc cctactgcct ggaatggtgc
ggtcccaggt cgcgggtcac 420gcggcggagg gggcgtggcc tgcccccggc ccagccggct
cttctttgcc tctgctggag 480tccggggagt ggcgttggct gctagagcga tgccgggccg
gagttgcgtc gccttagtcc 540tcctggctgc cgccgtcagc tgtgccgtcg cgcagcacgc
gccgccggtg agtgagcttg 600agccgaggcg cagagagggg cgtgcaggtg cgggcgcgga
tggaggcgca ggtgtggcgg 660cgcgagcggg tacaaggaac acctcgtgct gggcagcttc
tttacggggg tctgtggttt 720cgtgcacagg ggtgtgggtg cagagcgggc tggcgaaccc
cgtcctcggt agattcggtg 780ctacctgcaa ctagaactcc
800158800DNAHomo sapiens 158ggagttctag ttgcaggtag
caccgaatct accgaggacg gggttcgcca gcccgctctg 60cacccacacc cctgtgcacg
aaaccacaga cccccgtaaa gaagctgccc agcacgaggt 120gttccttgta cccgctcgcg
ccgccacacc tgcgcctcca tccgcgcccg cacctgcacg 180cccctctctg cgcctcggct
caagctcact caccggcggc gcgtgctgcg cgacggcaca 240gctgacggcg gcagccagga
ggactaaggc gacgcaactc cggcccggca tcgctctagc 300agccaacgcc actccccgga
ctccagcaga ggcaaagaag agccggctgg gccgggggca 360ggccacgccc cctccgccgc
gtgacccgcg acctgggacc gcaccattcc aggcagtagg 420gggaacgctc ggaggaggcg
ggactgggag gagaggacgg ggcttttcag tgccacgaaa 480agggtggcgt agagaaagag
agagagcctt ccaggctacc tgcagaagga gagtcgcgat 540cgcctttggc gcgtggcgtg
atccatcccc ctcccccacc gcgggcaata gtcggaccga 600gccggagccc cgccccgtag
gtggggccgg gagcttcacc cgtggcgcct cgatggggcg 660cctctagcag gcgggtgcag
cctgtcccgc gtacccaggc gtcctcggta cccacgaaac 720ggatccaaag agtctcaaca
ctaatgtaac atcccaccct gacccatctt tgccctctga 780gaaaagcggc ccgaaatgag
800159800DNAHomo sapiens
159ttctgcagag ccagcagccg gctcccacct acccaaggag agaagatcgc tccaagacag
60tgagagcttc cctgccattt cagtgcaaag tccctccgga gcgacctcag aggagtaacc
120gggccttaac tttttgcgct cgttttgcta taatttttct ctatccacct ccatcccacc
180cccacaacac tctttactgg gggggtcttt tgtgttccgg atctccccct ccatggctcc
240cttagccgaa gtcgggggct ttctgggcgg cctggagggc ttgggccagc aggtgggttc
300gcatttcctg ttgcctcctg ccggggagcg gccgccgctg ctgggcgagc gcaggagcgc
360ggcggagcgg agcgcgcgcg gcgggccggg ggctgcgcag ctggcgcacc tgcacggcat
420cctgcgccgc cggcagctct attgccgcac cggcttccac ctgcagatcc tgcccgacgg
480cagcgtgcag ggcacccggc aggaccacag cctcttcggt acgtactagc atcccgaccc
540cacccccatc tgcgccccag ctcggctcct cgttccctcc ccttgcacct ccctctttgc
600ctgccaaggg cgtcatcgcc gcgcggagcc cggagctccc ctggacccat ccggtgcaag
660acgcaggctg gggctgaagg gctggccaga gcagccgcgg ggagaaattt tcctgctggt
720ttgtcgccgc agcctctagc agggcagcag ctccagatgc tgggggcggg aggagaaagg
780gtgggcgctt cgcaagctcc
800160800DNAHomo sapiens 160ggagcttgcg aagcgcccac cctttctcct cccgccccca
gcatctggag ctgctgccct 60gctagaggct gcggcgacaa accagcagga aaatttctcc
ccgcggctgc tctggccagc 120ccttcagccc cagcctgcgt cttgcaccgg atgggtccag
gggagctccg ggctccgcgc 180ggcgatgacg cccttggcag gcaaagaggg aggtgcaagg
ggagggaacg aggagccgag 240ctggggcgca gatgggggtg gggtcgggat gctagtacgt
accgaagagg ctgtggtcct 300gccgggtgcc ctgcacgctg ccgtcgggca ggatctgcag
gtggaagccg gtgcggcaat 360agagctgccg gcggcgcagg atgccgtgca ggtgcgccag
ctgcgcagcc cccggcccgc 420cgcgcgcgct ccgctccgcc gcgctcctgc gctcgcccag
cagcggcggc cgctccccgg 480caggaggcaa caggaaatgc gaacccacct gctggcccaa
gccctccagg ccgcccagaa 540agcccccgac ttcggctaag ggagccatgg agggggagat
ccggaacaca aaagaccccc 600ccagtaaaga gtgttgtggg ggtgggatgg aggtggatag
agaaaaatta tagcaaaacg 660agcgcaaaaa gttaaggccc ggttactcct ctgaggtcgc
tccggaggga ctttgcactg 720aaatggcagg gaagctctca ctgtcttgga gcgatcttct
ctccttgggt aggtgggagc 780cggctgctgg ctctgcagaa
8001611300DNAHomo sapiens 161cttaaccccc ccatctccag
ttatcccaat gaaccgaccc cgagggggca tttccgctga 60agtccggggc tgtaaaaaat
taagtgagaa gagccgcgct aaagccaagc gtcgtcgtca 120cccaaggtac tgcgctgatg
cgctgcgggc cgaccaggtg ctcccgccgg ggcgtcttct 180cctacgcagg aagggccacg
ccgagagagg caggcaacaa gggcacggct ggaggccgga 240aggtcacccc gtccccggcg
gggcgggcgc ggcccagcct cacttcccgg gcacgttcgg 300gcggggcgat tgcagggaac
ggggcgggga ggcgacagtc cccggctccg ccgcgcgcca 360gcccgccttc gctgcccgga
ggcgccgcag gcctgggttc ccggacagct gagcccgagc 420gccgcctccc gaaaggtgaa
ggcggcccgg ggaggcgggg acggtgacgg gggcgggggc 480cgcgggcggt ctcccgacgg
ctgtcgcggg gccagcccaa agcccccgat ccccggtagc 540tgcgcttccc gcgcggggcg
ccggagtagg gcgggccaag ctggcctgcg gccgcggcgg 600gaagaagggc tagcgaagca
cccccgaccg ggcccaggcg ccggacgccg gggggcgcct 660cgctgcaact tctctttgga
agccccgaca cgagccccgg cccgcgcgcg cgctccccca 720cggccacgcg cgcaccctgc
cgcccgcacc cccgcgcgcc ctccgtctat tttttcctct 780tcctttcatc ctcacactct
aaaataggtc aaggggtgga agttacacct ggtgcagccc 840tcggctctga tgcaaaagca
gcttttgccc ctggctgcgg gacagcgctg tgactactcg 900caacgggaga gctgctgcca
gtcgccacac cgtgcggaaa gcgccggcga ccggagcact 960gacaatggtc tgcatagggg
agcggagaga agcttctgtt gcgccctaga tccgctgcct 1020cggcgcccgc ccgcagggag
gagggggcgc gacaggtcgt ctagcgcgtg ccccggagcc 1080cgcgcccggg tctggccgcc
tgggtgagtt cctgctcgtc ccctgccttt ccagtagccc 1140ggggtggctg tttaccttgc
aaacagcctt gcaatacgat caaaacaggc gagacagcca 1200tgcagtaagg gattgcggga
tgtgctttgg gtgtgagatt ggataaatca gaattcagag 1260ataaaggaca tgtctagtgc
cttaagggtt aaagtggatt 13001621300DNAHomo sapiens
162aatccacttt aacccttaag gcactagaca tgtcctttat ctctgaattc tgatttatcc
60aatctcacac ccaaagcaca tcccgcaatc ccttactgca tggctgtctc gcctgttttg
120atcgtattgc aaggctgttt gcaaggtaaa cagccacccc gggctactgg aaaggcaggg
180gacgagcagg aactcaccca ggcggccaga cccgggcgcg ggctccgggg cacgcgctag
240acgacctgtc gcgccccctc ctccctgcgg gcgggcgccg aggcagcgga tctagggcgc
300aacagaagct tctctccgct cccctatgca gaccattgtc agtgctccgg tcgccggcgc
360tttccgcacg gtgtggcgac tggcagcagc tctcccgttg cgagtagtca cagcgctgtc
420ccgcagccag gggcaaaagc tgcttttgca tcagagccga gggctgcacc aggtgtaact
480tccacccctt gacctatttt agagtgtgag gatgaaagga agaggaaaaa atagacggag
540ggcgcgcggg ggtgcgggcg gcagggtgcg cgcgtggccg tgggggagcg cgcgcgcggg
600ccggggctcg tgtcggggct tccaaagaga agttgcagcg aggcgccccc cggcgtccgg
660cgcctgggcc cggtcggggg tgcttcgcta gcccttcttc ccgccgcggc cgcaggccag
720cttggcccgc cctactccgg cgccccgcgc gggaagcgca gctaccgggg atcgggggct
780ttgggctggc cccgcgacag ccgtcgggag accgcccgcg gcccccgccc ccgtcaccgt
840ccccgcctcc ccgggccgcc ttcacctttc gggaggcggc gctcgggctc agctgtccgg
900gaacccaggc ctgcggcgcc tccgggcagc gaaggcgggc tggcgcgcgg cggagccggg
960gactgtcgcc tccccgcccc gttccctgca atcgccccgc ccgaacgtgc ccgggaagtg
1020aggctgggcc gcgcccgccc cgccggggac ggggtgacct tccggcctcc agccgtgccc
1080ttgttgcctg cctctctcgg cgtggccctt cctgcgtagg agaagacgcc ccggcgggag
1140cacctggtcg gcccgcagcg catcagcgca gtaccttggg tgacgacgac gcttggcttt
1200agcgcggctc ttctcactta attttttaca gccccggact tcagcggaaa tgccccctcg
1260gggtcggttc attgggataa ctggagatgg gggggttaag
13001631800DNAHomo sapiens 163ctagcattta ctggattcca gagtcttgtt atttaagaat
gcatcttaaa cggtactatc 60aaattcatgt tacgtgcagc ccagattgtt ttgggcagca
cgaaaagttt ctgaggcgct 120gcgtgtaccc caccccagga caccgtgtgt gcgcgccgag
ctgagtgcga ggaacgtggc 180gcgagggccg ggggatgccg ggctgcgtgg gtgtgagccc
tcgcgcgacc gcgaccccgc 240gcctctcccg ctctcgccgg aacgtgaccg cagccgcacc
tctcctccag ccctttccca 300gccagacgct tccttttagg tccttctggg cgtttattgt
aaattctgcg actaaaacac 360gccggtgagc ccggcccacc gacagatgga tcaatcgccc
ccttcccggc taggggagga 420ggaacccccc aaccccggag cctagggagc cgggagctgc
ctcgggacga gctcctcgga 480gcccagccgg ctgcggagcc ccggcccggg tcggtctcgg
ggccctcctg ccggggtggg 540gtgcgagccc ctgcccgatt cctctggggc ggttcaggca
ggtttgccgg cctccgagga 600ggtggtcagg gcgccctggc ccagcaggct tcttcccgag
ccggggggag gggagaccgg 660ctggggaagg ggcatctcga aggggtggag gccggggcgg
gcgggaggca agcgcgccgc 720gggcgtgagg gcaaagttcc cgaggtccgc gcggagagca
cacgtgtatg tgcgcgcggg 780gctaggccgg ggccggcagg atgcgttggg ttcgggggcg
cgcggggccg gcgccgaagg 840ggataattcc tttccctggc accatcgggg agacgctttg
tcggcctcgg ctcctgggcg 900cagggacgcc ttagcccacg gagggtggag cccccctcag
acccgggcca ccggctgggg 960tttttctaac gccctgcccc ccgagccccc ggatggctcg
ggccccacgg actccgcgcc 1020ctccagcctc agctcagctc cccaggcttc ccagacccag
cggcgcaggg ggcgggggca 1080ggggcagtgg gggttggagg gcgcagccgg tccccagggt
ggggagagct gcggggggag 1140gaggaggagg gtgccgacgc ttgagtgggt tcgagcccga
gccgtagccg ggggagccag 1200tcagtttccg gccaaggcag caggtcagtc ccaggaaggg
cgggcgattg agccgaggga 1260gccggcggct gggctctcct ctcggcccgc gatccccggc
gccgccgccg ccgccaccgc 1320caccgccacc gccttcgcct tgtcgccgcc gccgctgcag
agcatcgtag ctccgccgcg 1380ctcccgcgcc ccgcgccccg cgccgccagc cgcctgggag
cccgagcgcc gagcccgggg 1440cggaggagag gggcgctggc gcgagagccc gggcgaggga
gccgcgaagg gagaaggggg 1500cgggcggagg gaggagcagg gagagtggga gaagggggag
ggagagagga gagcgaggga 1560gagctggaga gagcgagagc aaagagcgag cgagggagag
gagagagaga gagaggagag 1620agaaagacac acgcacgcag agacacacgg tcactggaat
tccattagaa aaaagtgagc 1680cgagcaaggg ttagcgggag aagatttttt tgaatcttgt
cttcgtcttg gtgcgaaaga 1740agcgactcca gtctctcgtc ctcgaagctc cgactggatt
gttcttgggc gctgacaccc 18001641800DNAHomo sapiens 164gggtgtcagc
gcccaagaac aatccagtcg gagcttcgag gacgagagac tggagtcgct 60tctttcgcac
caagacgaag acaagattca aaaaaatctt ctcccgctaa cccttgctcg 120gctcactttt
ttctaatgga attccagtga ccgtgtgtct ctgcgtgcgt gtgtctttct 180ctctcctctc
tctctctctc ctctccctcg ctcgctcttt gctctcgctc tctccagctc 240tccctcgctc
tcctctctcc ctcccccttc tcccactctc cctgctcctc cctccgcccg 300cccccttctc
ccttcgcggc tccctcgccc gggctctcgc gccagcgccc ctctcctccg 360ccccgggctc
ggcgctcggg ctcccaggcg gctggcggcg cggggcgcgg ggcgcgggag 420cgcggcggag
ctacgatgct ctgcagcggc ggcggcgaca aggcgaaggc ggtggcggtg 480gcggtggcgg
cggcggcggc gccggggatc gcgggccgag aggagagccc agccgccggc 540tccctcggct
caatcgcccg cccttcctgg gactgacctg ctgccttggc cggaaactga 600ctggctcccc
cggctacggc tcgggctcga acccactcaa gcgtcggcac cctcctcctc 660ctccccccgc
agctctcccc accctgggga ccggctgcgc cctccaaccc ccactgcccc 720tgcccccgcc
ccctgcgccg ctgggtctgg gaagcctggg gagctgagct gaggctggag 780ggcgcggagt
ccgtggggcc cgagccatcc gggggctcgg ggggcagggc gttagaaaaa 840ccccagccgg
tggcccgggt ctgagggggg ctccaccctc cgtgggctaa ggcgtccctg 900cgcccaggag
ccgaggccga caaagcgtct ccccgatggt gccagggaaa ggaattatcc 960ccttcggcgc
cggccccgcg cgcccccgaa cccaacgcat cctgccggcc ccggcctagc 1020cccgcgcgca
catacacgtg tgctctccgc gcggacctcg ggaactttgc cctcacgccc 1080gcggcgcgct
tgcctcccgc ccgccccggc ctccacccct tcgagatgcc ccttccccag 1140ccggtctccc
ctccccccgg ctcgggaaga agcctgctgg gccagggcgc cctgaccacc 1200tcctcggagg
ccggcaaacc tgcctgaacc gccccagagg aatcgggcag gggctcgcac 1260cccaccccgg
caggagggcc ccgagaccga cccgggccgg ggctccgcag ccggctgggc 1320tccgaggagc
tcgtcccgag gcagctcccg gctccctagg ctccggggtt ggggggttcc 1380tcctccccta
gccgggaagg gggcgattga tccatctgtc ggtgggccgg gctcaccggc 1440gtgttttagt
cgcagaattt acaataaacg cccagaagga cctaaaagga agcgtctggc 1500tgggaaaggg
ctggaggaga ggtgcggctg cggtcacgtt ccggcgagag cgggagaggc 1560gcggggtcgc
ggtcgcgcga gggctcacac ccacgcagcc cggcatcccc cggccctcgc 1620gccacgttcc
tcgcactcag ctcggcgcgc acacacggtg tcctggggtg gggtacacgc 1680agcgcctcag
aaacttttcg tgctgcccaa aacaatctgg gctgcacgta acatgaattt 1740gatagtaccg
tttaagatgc attcttaaat aacaagactc tggaatccag taaatgctag
18001651300DNAHomo sapiens 165aaacagcatt agccttctcc catcaaaagt ccggaagctg
cccttcagtc gtcaaagtgt 60ttgccttaat ttgcaatcgt tatgacttga gccaaatgct
tatacctcat ttgtgtcgta 120tatgtgaaga tacaattgca aatcgttcac gaccttgagt
caagaccttg agtttcctga 180ggtcaggaga ccgttaggga atgtgagtgt cccagacggg
cgctgagccc agctcggaga 240cccaccccgc ccgtagcagc ggcgcgggcc ccagagagcc
ccgcactcgg ccgcgcctca 300gttacgctga ctcggctgtg cccgcagtgt cgcgctgtcg
cgtagccagg tgtcgccggg 360ctggcgcggt tatttatgac tgcgtggttg ggctgggggt
tcggggccgg ggagcagccg 420ggatccgccg cctcttccat gatcttcccg ggccgaacca
cgggaccgct acgctgaagg 480tggcgtcgcg ggtccccggg gccgcgcgag tgtaggggtc
gctctcggcc ggccgcgaag 540ctcgcggcac cgacttctcg cgagatttcg gcgacccccc
cccccgcccc cgcccctccg 600ttctctgccc cctcccagct ctggtgtggg cggcctccgc
tatggctgcg ctgcgaaggc 660tcttgtggcc gccaccccgg gtgtctcctc cactctgcgc
tcaccagccc ctccttgggc 720cgtgggggcg gcctgcggtg accaccctgg gccttcctgg
ccggcccttc tcctcccgag 780aggatgagga gagggctgtg gcggaggcgg catggaggcg
gcggcggcgc tggggggagc 840tgagcgtggc ggcggcggcc ggcggggggc tggtcggcct
ggtatgctac cagctgtacg 900gggaccccag ggccggctcg ccggcgaccg ggcgaccctc
aaagagcgcg gccacggagc 960ccgaggaccc gccccgcggc cgggggatgc tgcccatccc
agtggcggct gccaaggaga 1020cggtgagtgc gcgagcgcgc gtcacacctg cgcgggggat
gtgaccttcg tgccgggtac 1080gcaggaccct ggaggctgtg gggacggtgc aagcgctgtg
gccgcgggtg aggaacttcc 1140cgtgagcgag gctgacacct aggccggaca gcctaggatc
cggtcaccca cgtattggga 1200agaccagtga tgctgtccct gatgcatcag gaccttaaag
gtggctgcag ctaccaagta 1260tcaatccaaa cccaaaacca acacccctcc ccctcttaca
13001661300DNAHomo sapiens 166tgtaagaggg ggaggggtgt
tggttttggg tttggattga tacttggtag ctgcagccac 60ctttaaggtc ctgatgcatc
agggacagca tcactggtct tcccaatacg tgggtgaccg 120gatcctaggc tgtccggcct
aggtgtcagc ctcgctcacg ggaagttcct cacccgcggc 180cacagcgctt gcaccgtccc
cacagcctcc agggtcctgc gtacccggca cgaaggtcac 240atcccccgcg caggtgtgac
gcgcgctcgc gcactcaccg tctccttggc agccgccact 300gggatgggca gcatcccccg
gccgcggggc gggtcctcgg gctccgtggc cgcgctcttt 360gagggtcgcc cggtcgccgg
cgagccggcc ctggggtccc cgtacagctg gtagcatacc 420aggccgacca gccccccgcc
ggccgccgcc gccacgctca gctcccccca gcgccgccgc 480cgcctccatg ccgcctccgc
cacagccctc tcctcatcct ctcgggagga gaagggccgg 540ccaggaaggc ccagggtggt
caccgcaggc cgcccccacg gcccaaggag gggctggtga 600gcgcagagtg gaggagacac
ccggggtggc ggccacaaga gccttcgcag cgcagccata 660gcggaggccg cccacaccag
agctgggagg gggcagagaa cggaggggcg ggggcggggg 720ggggggtcgc cgaaatctcg
cgagaagtcg gtgccgcgag cttcgcggcc ggccgagagc 780gacccctaca ctcgcgcggc
cccggggacc cgcgacgcca ccttcagcgt agcggtcccg 840tggttcggcc cgggaagatc
atggaagagg cggcggatcc cggctgctcc ccggccccga 900acccccagcc caaccacgca
gtcataaata accgcgccag cccggcgaca cctggctacg 960cgacagcgcg acactgcggg
cacagccgag tcagcgtaac tgaggcgcgg ccgagtgcgg 1020ggctctctgg ggcccgcgcc
gctgctacgg gcggggtggg tctccgagct gggctcagcg 1080cccgtctggg acactcacat
tccctaacgg tctcctgacc tcaggaaact caaggtcttg 1140actcaaggtc gtgaacgatt
tgcaattgta tcttcacata tacgacacaa atgaggtata 1200agcatttggc tcaagtcata
acgattgcaa attaaggcaa acactttgac gactgaaggg 1260cagcttccgg acttttgatg
ggagaaggct aatgctgttt 13001671300DNAHomo sapiens
167cctggcgcgg acaggaccca gaaacaaacc acagcccggg gcgcagccgc cagggcgaag
60gttagttccg gtcccttccc ctcccctccc cacttggacg cgcttgcgga ggattgcgtt
120gacgagactc ttatttattg tcaccaacct gtggtggaat ttgcagttgc acattggatc
180tgattcgccc cgccccgaat gacgcctgcc cggaggcagt gaaagtacag ccgcgccgcc
240ccaagtcagc ctggacacat aaatcagcac gcggccggag aaccccgcaa tctctgcgcc
300cacaaaatac accgacgatg cccgatctac tttaagggct gaaacccacg ggcctgagag
360actataagag cgttccctac cgccatggaa caacggggac agaacgcccc ggccgcttcg
420ggggcccgga aaaggcacgg cccaggaccc agggaggcgc ggggagccag gcctgggccc
480cgggtcccca agacccttgt gctcgttgtc gccgcggtcc tgctgttggt gagtccccgc
540cgcggtccct ggctggggaa gagcgtgcct ggcgcctgga gagggcaggg agagaggggg
600acacggcggg ggtgcgtggc ccgggtcgcc tgcggccggg catgtccggg caagacgcac
660cagtcgtcgg agtcggggga agagatgggt ccccgggttg ggcaggagcg acctgggccg
720ccagggaaca gagcgcgcgc tccacttggt gtaaattccc gaatccagtg ggggagggcg
780acaaggaggg aattcccgag taagctgcgt gaagccacgg agaggtcgtc ggactttgat
840tttgttttct ttccttactt tctgtttctt tctctttttc tctttcttcc tttctttccc
900tcccttcctt cctcgctcag ttcctgcctt aatttctttt tcttttgcgc cttcgaatga
960attcctaaag gcgctcattg cagatcgctt tgaacctgcg gccggcgaag aactcccctg
1020tggtcgctgc ggcccagtgg ttccgttccg tgcgcgggag tcgtcgcggg cgcagctgga
1080gaggcccctt cccctcctta gcggctgcgc ccctacgcgt gcggggccgc tcatcgccaa
1140tgccattgtt tggggttcct tgggaaaacg agatttagga gaagggagtt gtggcacttg
1200gggcctgacc tgcttgataa tagcagctgc attttggcct gggaagagcc tttcttgcca
1260cctcttggca agtatccgtg ataatgggga agggacaaag
13001681300DNAHomo sapiens 168ctttgtccct tccccattat cacggatact tgccaagagg
tggcaagaaa ggctcttccc 60aggccaaaat gcagctgcta ttatcaagca ggtcaggccc
caagtgccac aactcccttc 120tcctaaatct cgttttccca aggaacccca aacaatggca
ttggcgatga gcggccccgc 180acgcgtaggg gcgcagccgc taaggagggg aaggggcctc
tccagctgcg cccgcgacga 240ctcccgcgca cggaacggaa ccactgggcc gcagcgacca
caggggagtt cttcgccggc 300cgcaggttca aagcgatctg caatgagcgc ctttaggaat
tcattcgaag gcgcaaaaga 360aaaagaaatt aaggcaggaa ctgagcgagg aaggaaggga
gggaaagaaa ggaagaaaga 420gaaaaagaga aagaaacaga aagtaaggaa agaaaacaaa
atcaaagtcc gacgacctct 480ccgtggcttc acgcagctta ctcgggaatt ccctccttgt
cgccctcccc cactggattc 540gggaatttac accaagtgga gcgcgcgctc tgttccctgg
cggcccaggt cgctcctgcc 600caacccgggg acccatctct tcccccgact ccgacgactg
gtgcgtcttg cccggacatg 660cccggccgca ggcgacccgg gccacgcacc cccgccgtgt
ccccctctct ccctgccctc 720tccaggcgcc aggcacgctc ttccccagcc agggaccgcg
gcggggactc accaacagca 780ggaccgcggc gacaacgagc acaagggtct tggggacccg
gggcccaggc ctggctcccc 840gcgcctccct gggtcctggg ccgtgccttt tccgggcccc
cgaagcggcc ggggcgttct 900gtccccgttg ttccatggcg gtagggaacg ctcttatagt
ctctcaggcc cgtgggtttc 960agcccttaaa gtagatcggg catcgtcggt gtattttgtg
ggcgcagaga ttgcggggtt 1020ctccggccgc gtgctgattt atgtgtccag gctgacttgg
ggcggcgcgg ctgtactttc 1080actgcctccg ggcaggcgtc attcggggcg gggcgaatca
gatccaatgt gcaactgcaa 1140attccaccac aggttggtga caataaataa gagtctcgtc
aacgcaatcc tccgcaagcg 1200cgtccaagtg gggaggggag gggaagggac cggaactaac
cttcgccctg gcggctgcgc 1260cccgggctgt ggtttgtttc tgggtcctgt ccgcgccagg
1300169800DNAHomo sapiens 169tgcccctttt ctgagtgctt
ggaagtgact gctgcaagtg acaagtgacc acgccttttc 60ccccgcgggt ataaattcag
aggcgctgcg ctccgattct ggcagtgcag ctgtgggaac 120ctctccacgc gcacgaactc
agccaacgat ttctgataga tttttgggag tttgaccaga 180gatgcaaggg gtgaaggagc
gcttcctacc gttagggaac tctggggaca gagcgccccg 240gccgcctgat ggccgaggca
gggtgcgacc caggacccag gacggcgtcg ggaaccatac 300catggcccgg atccccaaga
ccctaaagtt cgtcgtcgtc atcgtcgcgg tcctgctgcc 360agtgagtccc ggccgcggtc
cctggctggg gaagagcgca cctggcgccg ggagggggca 420gggagacggg gacacggcag
ggatgcctgg ccctggtcac ctgcggccgg gcatgtccgg 480gcaggacgaa ctcgccgtcg
gagtcagggg aagaactggg tccccgggct gggcaggagg 540gacccggccg cgagggagca
gagaggcggt ccccctggct gccccgagcc cgcgaaggga 600gggaagttcc agaatcgaga
gagggaggga gtcaaggtgg aacccataga gtgagcctcc 660tgaagacaca gagcggttgc
ctctctcatt aattaattaa ttagttaata aaattaaccc 720catgtttaca ttcttaaacg
tgttccttgg agatcggttt aaccaacagc cagtgaaaaa 780acttttcagc gctgtcttta
800170800DNAHomo sapiens
170taaagacagc gctgaaaagt tttttcactg gctgttggtt aaaccgatct ccaaggaaca
60cgtttaagaa tgtaaacatg gggttaattt tattaactaa ttaattaatt aatgagagag
120gcaaccgctc tgtgtcttca ggaggctcac tctatgggtt ccaccttgac tccctccctc
180tctcgattct ggaacttccc tcccttcgcg ggctcggggc agccaggggg accgcctctc
240tgctccctcg cggccgggtc cctcctgccc agcccgggga cccagttctt cccctgactc
300cgacggcgag ttcgtcctgc ccggacatgc ccggccgcag gtgaccaggg ccaggcatcc
360ctgccgtgtc cccgtctccc tgccccctcc cggcgccagg tgcgctcttc cccagccagg
420gaccgcggcc gggactcact ggcagcagga ccgcgacgat gacgacgacg aactttaggg
480tcttggggat ccgggccatg gtatggttcc cgacgccgtc ctgggtcctg ggtcgcaccc
540tgcctcggcc atcaggcggc cggggcgctc tgtccccaga gttccctaac ggtaggaagc
600gctccttcac cccttgcatc tctggtcaaa ctcccaaaaa tctatcagaa atcgttggct
660gagttcgtgc gcgtggagag gttcccacag ctgcactgcc agaatcggag cgcagcgcct
720ctgaatttat acccgcgggg gaaaaggcgt ggtcacttgt cacttgcagc agtcacttcc
780aagcactcag aaaaggggca
8001711300DNAHomo sapiens 171gaaataactt gagccaggga tcaaacacta agattggcag
gaaatgagca ggaagaggta 60gcggggtccc tgacgccatc tattcaattg tttttcagaa
gaggtatcag ctcttgaagg 120cttacttctc aatactggct gcgagagcaa gaatggtgtg
taatttacaa aagccgtcat 180tgctgtaggt aagttgtagc aaacgactcg cgcccgagca
ttcccgcccc cgccttcgct 240gcggccccgc ccacgacgac cctggggaac tacaagtccc
gccatacagc ggggagcgcc 300cggagctcgc gccggccccg cccccagccc ggtccccacc
cccggctccg cccccggccc 360cctcccgccg ggtcaacccc gaagagtcgc cggtggccgc
ggcagacgga agccgaacga 420gttcctcggc ggctgcagga tgggggactc caaagtgaaa
gtggcggtgc ggatacgacc 480catgaaccgg cgaggtgaga gccgagccct cctgggccgc
cggggcggag gcggcaggtg 540cctggcgcgc ccttccctcg gccgccgtgg ggggtccggc
ggccccgccc ctatagtcag 600cggcggggcg cgaggagggg cccggggacc ctgaaacccg
ctcccgcgct gagacgcccg 660gctccctctt ctcccctccc ttcccccctg gccagccccg
tccctggcgc cgtcgggccc 720ctcgtgccgg ccccgctgcc ccttccgcct gcgcccgccc
cgcccctgcg cccttttgcc 780ctctcgtctc ccccggaggt tcccgagggc gccctcggcc
ctcgcgccca gcctcgtcct 840ggcccctcag cctcgctcct tccccgccag ctgtcatcgt
cgcccccgcg cgcgggtcgc 900cagcccctgc agcccgcctc gggaccgccc gggacccccc
gggaccccgc gtctcgcccg 960ggtcgcccaa gcctgcaccg ccttggcccg cggcgggaag
aagggcaggg ggccaggcgg 1020gtgccccgcg gcgagttcct tccacctggg cgtcctgaga
ttggggtcag gtggaggaga 1080tgcccttttc gttgtttttg gacagttgag aaagttttgg
ttttgcctga agtctcattc 1140atcatctctc aataaatagc taaagtgcca agattcttgt
ggaattgtat ctttctgaca 1200ttctcttaac tctgcaggga gtgtagagaa ggcagataaa
ccgagtacat ttaaataatc 1260tgtagacccg gggagtggag agaaccccaa aagtcagggg
13001721300DNAHomo sapiens 172cccctgactt ttggggttct
ctccactccc cgggtctaca gattatttaa atgtactcgg 60tttatctgcc ttctctacac
tccctgcaga gttaagagaa tgtcagaaag atacaattcc 120acaagaatct tggcacttta
gctatttatt gagagatgat gaatgagact tcaggcaaaa 180ccaaaacttt ctcaactgtc
caaaaacaac gaaaagggca tctcctccac ctgaccccaa 240tctcaggacg cccaggtgga
aggaactcgc cgcggggcac ccgcctggcc ccctgccctt 300cttcccgccg cgggccaagg
cggtgcaggc ttgggcgacc cgggcgagac gcggggtccc 360ggggggtccc gggcggtccc
gaggcgggct gcaggggctg gcgacccgcg cgcgggggcg 420acgatgacag ctggcgggga
aggagcgagg ctgaggggcc aggacgaggc tgggcgcgag 480ggccgagggc gccctcggga
acctccgggg gagacgagag ggcaaaaggg cgcaggggcg 540gggcgggcgc aggcggaagg
ggcagcgggg ccggcacgag gggcccgacg gcgccaggga 600cggggctggc caggggggaa
gggaggggag aagagggagc cgggcgtctc agcgcgggag 660cgggtttcag ggtccccggg
cccctcctcg cgccccgccg ctgactatag gggcggggcc 720gccggacccc ccacggcggc
cgagggaagg gcgcgccagg cacctgccgc ctccgccccg 780gcggcccagg agggctcggc
tctcacctcg ccggttcatg ggtcgtatcc gcaccgccac 840tttcactttg gagtccccca
tcctgcagcc gccgaggaac tcgttcggct tccgtctgcc 900gcggccaccg gcgactcttc
ggggttgacc cggcgggagg gggccggggg cggagccggg 960ggtggggacc gggctggggg
cggggccggc gcgagctccg ggcgctcccc gctgtatggc 1020gggacttgta gttccccagg
gtcgtcgtgg gcggggccgc agcgaaggcg ggggcgggaa 1080tgctcgggcg cgagtcgttt
gctacaactt acctacagca atgacggctt ttgtaaatta 1140cacaccattc ttgctctcgc
agccagtatt gagaagtaag ccttcaagag ctgatacctc 1200ttctgaaaaa caattgaata
gatggcgtca gggaccccgc tacctcttcc tgctcatttc 1260ctgccaatct tagtgtttga
tccctggctc aagttatttc 13001731550DNAHomo sapiens
173accccctcct tccttctttc cctaccgccc cacgcgcgac ccggggatgg ctccgtggcc
60tcacgagaac agctctcttg ccccatggcc ggacctcccc accctggcgc ccaataccgc
120caacaccagt gggctgccag gggttccgtg ggaggcggcc ctagccgggg ccctgctggc
180gctggcggtg ctggccaccg tgggaggcaa cctgctggtc atcgtggcca tcgcctggac
240tccgagactc cagaccatga ccaacgtgtt cgtgacttcg ctggccgcag ccgacctggt
300gatgggactc ctggtggtgc cgccggcggc caccttggcg ctgactggcc actggccgtt
360gggcgccact ggctgcgagc tgtggacctc ggtggacgtg ctgtgtgtga ccgccagcat
420cgaaaccctg tgcgccctgg ccgtggaccg ctacctggct gtgaccaacc cgctgcgtta
480cggcgcactg gtcaccaagc gctgcgcccg gacagctgtg gtcctggtgt gggtcgtgtc
540ggccgcggtg tcgtttgcgc ccatcatgag ccagtggtgg cgcgtagggg ccgacgccga
600ggcgcagcgc tgccactcca acccgcgctg ctgtgccttc gcctccaaca tgccctacgt
660gctgctgtcc tcctccgtct ccttctacct tcctcttctc gtgatgctct tcgtctacgc
720gcgggttttc gtggtggcta cgcgccagct gcgcttgctg cgcggggagc tgggccgctt
780tccgcccgag gagtctccgc cggcgccgtc gcgctctctg gccccggccc cggtggggac
840gtgcgctccg cccgaagggg tgcccgcctg cggccggcgg cccgcgcgcc tcctgcctct
900ccgggaacac cgggccctgt gcaccttggg tctcatcatg ggcaccttca ctctctgctg
960gttgcccttc tttctggcca acgtgctgcg cgccctgggg ggcccctctc tagtcccggg
1020cccggctttc cttgccctga actggctagg ttatgccaat tctgccttca acccgctcat
1080ctactgccgc agcccggact ttcgcagcgc cttccgccgt cttctgtgcc gctgcggccg
1140tcgcctgcct ccggagccct gcgccgccgc ccgcccggcc ctcttcccct cgggcgttcc
1200tgcggcccgg agcagcccag cgcagcccag gctttgccaa cggctcgacg ggtaggtaac
1260cggggcagag ggaccggcgg ctcagggtcg ggaagcatgc gatgtgtccg tgggtcaact
1320ttttgagtgt ggagtttatt aagagaaggt gggatggctt tgcttggaga gaaaagggaa
1380cgaggagtag cgaaccaaaa tgggacccag ggtccttttc tttccggatc cagtcactag
1440ggtagaagca aaggagggcg agcgggccgt cgttcctcac ccaaggaccc aaggtgcgcc
1500accggaaagc gctgcggtgt cccgaggact ctcgcctcgc ctggtcggct
15501741550DNAHomo sapiens 174agccgaccag gcgaggcgag agtcctcggg acaccgcagc
gctttccggt ggcgcacctt 60gggtccttgg gtgaggaacg acggcccgct cgccctcctt
tgcttctacc ctagtgactg 120gatccggaaa gaaaaggacc ctgggtccca ttttggttcg
ctactcctcg ttcccttttc 180tctccaagca aagccatccc accttctctt aataaactcc
acactcaaaa agttgaccca 240cggacacatc gcatgcttcc cgaccctgag ccgccggtcc
ctctgccccg gttacctacc 300cgtcgagccg ttggcaaagc ctgggctgcg ctgggctgct
ccgggccgca ggaacgcccg 360aggggaagag ggccgggcgg gcggcggcgc agggctccgg
aggcaggcga cggccgcagc 420ggcacagaag acggcggaag gcgctgcgaa agtccgggct
gcggcagtag atgagcgggt 480tgaaggcaga attggcataa cctagccagt tcagggcaag
gaaagccggg cccgggacta 540gagaggggcc ccccagggcg cgcagcacgt tggccagaaa
gaagggcaac cagcagagag 600tgaaggtgcc catgatgaga cccaaggtgc acagggcccg
gtgttcccgg agaggcagga 660ggcgcgcggg ccgccggccg caggcgggca ccccttcggg
cggagcgcac gtccccaccg 720gggccggggc cagagagcgc gacggcgccg gcggagactc
ctcgggcgga aagcggccca 780gctccccgcg cagcaagcgc agctggcgcg tagccaccac
gaaaacccgc gcgtagacga 840agagcatcac gagaagagga aggtagaagg agacggagga
ggacagcagc acgtagggca 900tgttggaggc gaaggcacag cagcgcgggt tggagtggca
gcgctgcgcc tcggcgtcgg 960cccctacgcg ccaccactgg ctcatgatgg gcgcaaacga
caccgcggcc gacacgaccc 1020acaccaggac cacagctgtc cgggcgcagc gcttggtgac
cagtgcgccg taacgcagcg 1080ggttggtcac agccaggtag cggtccacgg ccagggcgca
cagggtttcg atgctggcgg 1140tcacacacag cacgtccacc gaggtccaca gctcgcagcc
agtggcgccc aacggccagt 1200ggccagtcag cgccaaggtg gccgccggcg gcaccaccag
gagtcccatc accaggtcgg 1260ctgcggccag cgaagtcacg aacacgttgg tcatggtctg
gagtctcgga gtccaggcga 1320tggccacgat gaccagcagg ttgcctccca cggtggccag
caccgccagc gccagcaggg 1380ccccggctag ggccgcctcc cacggaaccc ctggcagccc
actggtgttg gcggtattgg 1440gcgccagggt ggggaggtcc ggccatgggg caagagagct
gttctcgtga ggccacggag 1500ccatccccgg gtcgcgcgtg gggcggtagg gaaagaagga
aggagggggt 15501751800DNAHomo sapiens 175cgcagaccca
gcaggagagc gcaacctagc atctttaagg ttcgcttagc ccttcctgtg 60cacctggaag
gaagccttat cttaaactcc cttccaccta gagtttattt tcgcctgcgt 120gcgacagggc
ttttgtactt aagtgagtta aggaatgaac cccgaactct tctgggaaag 180ccaccaacgt
tccccccgca cccctcccag ggttcctgac cacggagact ctgcttgggg 240cacaggtgtg
ggagtcgcaa acttttctct gcgccgtcct tttccgcgtg gaatgggacg 300gagcagccct
cccaggcgct gcctggctgc ggaggggagc gggcagcgag agcctcgggt 360ctccgcctgg
gttcccgggt ctccggggcg ctggcctcgg tctccgcgca gcgtccagcg 420acccctgtcg
ggggttcccg gcagccgcgc cgccaccccc cgcccggcca gcgcgggagg 480aaaaggggct
gcgcccggga gcgccgagcc caggctcctc ccggtggcgt gtccgcgcct 540cggggtgggg
gtgtggtggg gaagagggag ggggcgaggc caggggaggg tgcgaaggag 600gcgcctgcct
ccaacctgcg ggcgggaggt gggtggctgc ggggcaattg aaaaagagcc 660ggcgaggagt
tccccgaaac ttgttggaac tccgggctcg cgcggaggcc aggagctgag 720cggcggcggc
tgccggacga tgggagcgtg agcaggacgg tgataacctc tccccgatcg 780ggttgcgagg
gcgccgggca gaggccagga cgcgagccgc cagcggtggg acccatcgac 840gacttcccgg
ggcgacagga gcagccccga gagccagggc gagcgcccgt tccaggtggc 900cggaccgccc
gccgcgtccg cgccgcgctc cctgcaggca acgggagacg cccccgcgca 960gcgcgagcgc
ctcagcgcgg ccgctcgctc tccccctcga gggacaaact tttcccaaac 1020ccgatccgag
cccttggacc aaactcgcct gcgccgagag ccgtccgcgt agagcgctcc 1080gtctccggcg
agatgtccga gcgcaaagaa ggcagaggca aagggaaggg caagaagaag 1140gagcgaggct
ccggcaagaa gccggagtcc gcggcgggca gccagagccc aggtgggtgc 1200gcagcgcggc
ccgggcccca cgatcctcct cctgctcctc ctactcctcc tcctcctcgg 1260atgccgtggc
ctctccctcc ccctctccct cgcccgtcct cttcgccctg cgctctgagc 1320gcccgttgag
tcgcgcggtg cttcccctcc tgggggccgc cgctcacctg ggcgccgagt 1380cctaccgggc
gcctacgccc agagctcagg gcaagggaca gcagtcccgg ccgcaccctc 1440ccagagtccc
gggagcgctt cgctccctgg cacggcccct ccccagcgcc ttagcggctg 1500agcccagccc
gggagtggga cctgggctat aggagtcgag gctgcgtgcg cgcgtgcccc 1560gcgccataag
cgctttgcac gggggccgtg tgccctctag cgggaaacgc tggaatgggc 1620cgcctggagg
gagagccggt cccctcggtg tgcctggcag cgcagaagtg ggtggtcgag 1680caagaggccg
cgtgggaagt tagcttcggc gttttggggc acagggcaag cgatgtagag 1740tgcgcgccgg
ttcatcttga ttcagtcctg tgctacggag actcaagagc agcggcaggg
18001761800DNAHomo sapiens 176ccctgccgct gctcttgagt ctccgtagca caggactgaa
tcaagatgaa ccggcgcgca 60ctctacatcg cttgccctgt gccccaaaac gccgaagcta
acttcccacg cggcctcttg 120ctcgaccacc cacttctgcg ctgccaggca caccgagggg
accggctctc cctccaggcg 180gcccattcca gcgtttcccg ctagagggca cacggccccc
gtgcaaagcg cttatggcgc 240ggggcacgcg cgcacgcagc ctcgactcct atagcccagg
tcccactccc gggctgggct 300cagccgctaa ggcgctgggg aggggccgtg ccagggagcg
aagcgctccc gggactctgg 360gagggtgcgg ccgggactgc tgtcccttgc cctgagctct
gggcgtaggc gcccggtagg 420actcggcgcc caggtgagcg gcggccccca ggaggggaag
caccgcgcga ctcaacgggc 480gctcagagcg cagggcgaag aggacgggcg agggagaggg
ggagggagag gccacggcat 540ccgaggagga ggaggagtag gaggagcagg aggaggatcg
tggggcccgg gccgcgctgc 600gcacccacct gggctctggc tgcccgccgc ggactccggc
ttcttgccgg agcctcgctc 660cttcttcttg cccttccctt tgcctctgcc ttctttgcgc
tcggacatct cgccggagac 720ggagcgctct acgcggacgg ctctcggcgc aggcgagttt
ggtccaaggg ctcggatcgg 780gtttgggaaa agtttgtccc tcgaggggga gagcgagcgg
ccgcgctgag gcgctcgcgc 840tgcgcggggg cgtctcccgt tgcctgcagg gagcgcggcg
cggacgcggc gggcggtccg 900gccacctgga acgggcgctc gccctggctc tcggggctgc
tcctgtcgcc ccgggaagtc 960gtcgatgggt cccaccgctg gcggctcgcg tcctggcctc
tgcccggcgc cctcgcaacc 1020cgatcgggga gaggttatca ccgtcctgct cacgctccca
tcgtccggca gccgccgccg 1080ctcagctcct ggcctccgcg cgagcccgga gttccaacaa
gtttcgggga actcctcgcc 1140ggctcttttt caattgcccc gcagccaccc acctcccgcc
cgcaggttgg aggcaggcgc 1200ctccttcgca ccctcccctg gcctcgcccc ctccctcttc
cccaccacac ccccaccccg 1260aggcgcggac acgccaccgg gaggagcctg ggctcggcgc
tcccgggcgc agcccctttt 1320cctcccgcgc tggccgggcg gggggtggcg gcgcggctgc
cgggaacccc cgacaggggt 1380cgctggacgc tgcgcggaga ccgaggccag cgccccggag
acccgggaac ccaggcggag 1440acccgaggct ctcgctgccc gctcccctcc gcagccaggc
agcgcctggg agggctgctc 1500cgtcccattc cacgcggaaa aggacggcgc agagaaaagt
ttgcgactcc cacacctgtg 1560ccccaagcag agtctccgtg gtcaggaacc ctgggagggg
tgcgggggga acgttggtgg 1620ctttcccaga agagttcggg gttcattcct taactcactt
aagtacaaaa gccctgtcgc 1680acgcaggcga aaataaactc taggtggaag ggagtttaag
ataaggcttc cttccaggtg 1740cacaggaagg gctaagcgaa ccttaaagat gctaggttgc
gctctcctgc tgggtctgcg 18001771550DNAHomo sapiens 177gggagggtgg
cctgcaaggc ggggccggtt gcggtcaagt tcaagtaggg tcagagcagg 60agaacactgg
cataaaaaat agccacatcc aaggaagcag tgaggtgtgg ggaccatcta 120tttcggtggg
ccttcccacc cccaggccgg ccttcccatc acgcgtgggt gtgggggcac 180tgcccccgct
gcgcgcagga acagcgggga gagccaggag cggagcggct tcgggatgcc 240agactgagca
gtgggttcgt ctgcggccac ctctcaggga acaagcttcc ccccgcggag 300actctgcttc
ttttaaaagc cttcctgggt ttagtctagg gcgacaggac gacctccctt 360gggaagggag
agcctgccag tccccctccc attcgccagg cggtgcagcc cctcctcccg 420cccggggcgc
gcgcacctca gcgtcgcggg cctagcgccc agcagccgcg ccccaggccg 480ggcctcgggt
tccgggagcc cgcaggcgcg cgcccggccg ggcgtgtcgg gagcgcgcgg 540cggccggggg
cggagcgcag ccagggctgc gcggcgcgcc ccggctcccg cccgctccca 600gccgggcccc
ccagcggtcg gcgggacggc tcccggctgc agtctgcccg cccgccccgc 660gcgggggccg
agtcgcgaag cgcgcctgcg acccggcgtc cgggcgcgct ggagaggacg 720cgaggagcca
tgaggcgcca gcctgcgaag gtggcggcgc tgctgctcgg gctgctcttg 780gaggtagggg
ccggggaccg ggtgctgccg gaggcgcggc gcccaccatg ctggcggctg 840ggggcgcgca
gttccgaggc gccccagagg accttgcctg ggagcgcaga cggtggagcg 900acggggagcc
acagccctgc gcgcctcccg gagctgggag gtgcgggacc ctggtgacgg 960ggaggctccc
gccccggtcc gcgccttccg tcgttccttc ggttttcgca ccccgccccc 1020accctgcggg
tgagcgcgtt tcccgcgccg accgcctccg ttagctcggg gtgacctttg 1080tgcaccgtcc
gccccctctc cccgccgcag agggccgagg atcggatgga cccggggttg 1140ggcgggggtg
gtcctcgggc gcggcgcagg cgcggagagc ccggggcgcc gggcagtttg 1200gggttaggaa
aggatgggtg ccgagccggg gtgaggggag cgggcggagg ggactgtggg 1260gaagtgtcgc
gggagtgccg ggagttgtgg aggtgagcag cgggaggagg cgttcccgcg 1320tgtgaaaatg
aagtgcagcc tttaggtgcg gggaggaaat tctgcggaga gcctggctgg 1380gtgggggtgc
ggagccgaag ccggcgggga acttgttgag cggcttccgg gtgcgagcgc 1440ccgtgaccgc
atccctggcg gggaccgcgg ctgctcctgg ctgtgaaatt gcatcctcgg 1500atggggccac
atacttctca ctaaagcagg ttccttaaaa tgcgaactag
15501781550DNAHomo sapiens 178ctagttcgca ttttaaggaa cctgctttag tgagaagtat
gtggccccat ccgaggatgc 60aatttcacag ccaggagcag ccgcggtccc cgccagggat
gcggtcacgg gcgctcgcac 120ccggaagccg ctcaacaagt tccccgccgg cttcggctcc
gcacccccac ccagccaggc 180tctccgcaga atttcctccc cgcacctaaa ggctgcactt
cattttcaca cgcgggaacg 240cctcctcccg ctgctcacct ccacaactcc cggcactccc
gcgacacttc cccacagtcc 300cctccgcccg ctcccctcac cccggctcgg cacccatcct
ttcctaaccc caaactgccc 360ggcgccccgg gctctccgcg cctgcgccgc gcccgaggac
cacccccgcc caaccccggg 420tccatccgat cctcggccct ctgcggcggg gagagggggc
ggacggtgca caaaggtcac 480cccgagctaa cggaggcggt cggcgcggga aacgcgctca
cccgcagggt gggggcgggg 540tgcgaaaacc gaaggaacga cggaaggcgc ggaccggggc
gggagcctcc ccgtcaccag 600ggtcccgcac ctcccagctc cgggaggcgc gcagggctgt
ggctccccgt cgctccaccg 660tctgcgctcc caggcaaggt cctctggggc gcctcggaac
tgcgcgcccc cagccgccag 720catggtgggc gccgcgcctc cggcagcacc cggtccccgg
cccctacctc caagagcagc 780ccgagcagca gcgccgccac cttcgcaggc tggcgcctca
tggctcctcg cgtcctctcc 840agcgcgcccg gacgccgggt cgcaggcgcg cttcgcgact
cggcccccgc gcggggcggg 900cgggcagact gcagccggga gccgtcccgc cgaccgctgg
ggggcccggc tgggagcggg 960cgggagccgg ggcgcgccgc gcagccctgg ctgcgctccg
cccccggccg ccgcgcgctc 1020ccgacacgcc cggccgggcg cgcgcctgcg ggctcccgga
acccgaggcc cggcctgggg 1080cgcggctgct gggcgctagg cccgcgacgc tgaggtgcgc
gcgccccggg cgggaggagg 1140ggctgcaccg cctggcgaat gggaggggga ctggcaggct
ctcccttccc aagggaggtc 1200gtcctgtcgc cctagactaa acccaggaag gcttttaaaa
gaagcagagt ctccgcgggg 1260ggaagcttgt tccctgagag gtggccgcag acgaacccac
tgctcagtct ggcatcccga 1320agccgctccg ctcctggctc tccccgctgt tcctgcgcgc
agcgggggca gtgcccccac 1380acccacgcgt gatgggaagg ccggcctggg ggtgggaagg
cccaccgaaa tagatggtcc 1440ccacacctca ctgcttcctt ggatgtggct attttttatg
ccagtgttct cctgctctga 1500ccctacttga acttgaccgc aaccggcccc gccttgcagg
ccaccctccc 1550179800DNAHomo sapiens 179tgctgggcaa
tgcgtgcgtg gtggctgcca tcgccttgga gcgctccctg cagaacgtgg 60ccaattatct
tattggctct ttggcggtca ccgacctcat ggtgtcggtg ttggtgctgc 120ccatggccgc
gctgtatcag gtgctcaaca agtggacact gggccaggta acctgcgacc 180tgttcatcgc
cctcgacgtg ctgtgctgca cctcatccat cttgcacctg tgcgccatcg 240cgctggacag
gtactgggcc atcacggacc ccatcgacta cgtgaacaag aggacgcccc 300ggcgcgccgc
tgcgctcatc tcgctcactt ggcttattgg cttcctcatc tctatcccgc 360ccatgctggg
ctggcgcacc ccggaagacc gctcggaccc cgacgcatgc accattagca 420aggatcatgg
ctacactatc tattccacct ttggagcttt ctacatcccg ctgctgctca 480tgctggttct
ctatgggcgc atattccgag ctgcgcgctt ccgcatccgc aagacggtca 540aaaaggtgga
gaagaccgga gcggacaccc gccatggagc atctcccgcc ccgcagccca 600agaagagtgt
gaatggagag tcggggagca ggaactggag gctgggcgtg gagagcaagg 660ctgggggtgc
tctgtgcgcc aatggcgcgg tgaggcaagg tgacgatggc gccgccctgg 720aggtgatcga
ggtgcaccga gtgggcaact ccaaagagca cttgcctctg cccagcgagg 780ctggtcctac
cccttgtgcc
800180800DNAHomo sapiens 180ggcacaaggg gtaggaccag cctcgctggg cagaggcaag
tgctctttgg agttgcccac 60tcggtgcacc tcgatcacct ccagggcggc gccatcgtca
ccttgcctca ccgcgccatt 120ggcgcacaga gcacccccag ccttgctctc cacgcccagc
ctccagttcc tgctccccga 180ctctccattc acactcttct tgggctgcgg ggcgggagat
gctccatggc gggtgtccgc 240tccggtcttc tccacctttt tgaccgtctt gcggatgcgg
aagcgcgcag ctcggaatat 300gcgcccatag agaaccagca tgagcagcag cgggatgtag
aaagctccaa aggtggaata 360gatagtgtag ccatgatcct tgctaatggt gcatgcgtcg
gggtccgagc ggtcttccgg 420ggtgcgccag cccagcatgg gcgggataga gatgaggaag
ccaataagcc aagtgagcga 480gatgagcgca gcggcgcgcc ggggcgtcct cttgttcacg
tagtcgatgg ggtccgtgat 540ggcccagtac ctgtccagcg cgatggcgca caggtgcaag
atggatgagg tgcagcacag 600cacgtcgagg gcgatgaaca ggtcgcaggt tacctggccc
agtgtccact tgttgagcac 660ctgatacagc gcggccatgg gcagcaccaa caccgacacc
atgaggtcgg tgaccgccaa 720agagccaata agataattgg ccacgttctg cagggagcgc
tccaaggcga tggcagccac 780cacgcacgca ttgcccagca
800181550DNAHomo sapiens 181tgacgcaagg tccagtccag
attgccaggc ccggggcatg agagaggatc cttgtaggtt 60tcggaggtgg gggggctgca
ctccattgtt cactccgggc caatcagggt tggcccactt 120cctcccagcc aatctccctt
cacccccagc ctccaaccca acccaccccg cccatcagcc 180cctggatccc catcacctcc
cccgcatccc cggcagttct ggggaagctt cgtgacgcca 240caggtcccgc ccccagctcc
ggcccggggc tagtgcgtgt tgacgtcatg ctgcgtgcgg 300gccggtgcgg aatcgctcct
tcaactccgc ggggcagtag gagttagtta gcaaagagcc 360gaggccgggc gcgcgaccct
cgtccttctg cccctggccg cacactttgc gcacatctct 420ttttctgcat ggtggatatt
atttttcatt atccttttct gggtgctatg ggtgatcatt 480ccaagagtaa gtatttctgt
gtgtgtgtgg ggtggggtgt gtgtgtatgc ttaatatgca 540aaatttctaa
550182550DNAHomo sapiens
182ttagaaattt tgcatattaa gcatacacac acaccccacc ccacacacac acagaaatac
60ttactcttgg aatgatcacc catagcaccc agaaaaggat aatgaaaaat aatatccacc
120atgcagaaaa agagatgtgc gcaaagtgtg cggccagggg cagaaggacg agggtcgcgc
180gcccggcctc ggctctttgc taactaactc ctactgcccc gcggagttga aggagcgatt
240ccgcaccggc ccgcacgcag catgacgtca acacgcacta gccccgggcc ggagctgggg
300gcgggacctg tggcgtcacg aagcttcccc agaactgccg gggatgcggg ggaggtgatg
360gggatccagg ggctgatggg cggggtgggt tgggttggag gctgggggtg aagggagatt
420ggctgggagg aagtgggcca accctgattg gcccggagtg aacaatggag tgcagccccc
480ccacctccga aacctacaag gatcctctct catgccccgg gcctggcaat ctggactgga
540ccttgcgtca
5501831050DNAHomo sapiens 183cagggaacag acccagtagt tggcttggat ctcttaactc
cagaaaaggc cgagtgagga 60caagggagac cacagggata atttctgtgg ctctggtaag
gggatgacaa gggagaaaaa 120ctttcccacg gttccgtctg gcccgcggcg cttgtctgcc
tgcgcggggt caaagcccgg 180cgccgcccac gcgcggctcg ggtgggaacc cgcagacgtg
gggcgagcag ggccgctggc 240tgtggcgggc gagcgccggg gcgccacgtc cgaggccgcg
gggtcggggc tgcaggcaca 300gctcgagcgc tttccgcggg gtttggctcc tgtcgcttcc
cgtctcgccg aaccggcatc 360gccgccgccg gagccgcagc gagtcctcag agcctggctg
ctggcggccg ggagcgccgg 420gacggggcgc gaagccggag gctccgggac gtggatacag
gtaaaggccg gcgggtcgga 480gtcgggcggg gcgcggcggc ggcgcctctc ggagggacct
ggcctcggcc gggccctacc 540cagccgcggt ggcccgggcc cccacgttgg cccaggcggg
gacgtgccaa ggggctgggc 600tagggttgcc gctggcctgg ccgcctctcg cccggcgggc
ctcaggtgac gcggccgcgg 660cttaactttc gcacctgagg ctctcggagc ggcctcgggg
cgcgcccacc tggaggttgg 720aattacacag ggtcgaaaaa gctgagtcct ggaggcgagg
cgctgtaggt gtggcggagg 780aggccgggga aggtggggtg ggtgccaggg gtccagtact
gaaccctctc caggtctgag 840gtggggaact gcgtcttgtt taatttcgga gcttgtgggg
accacacagc cccttccacg 900gccgattccc tctgcacggt tccactttcc tttgtctagc
ccatttcagt atcggcgtcg 960cagtcgcttt tgttgcagcc ttgggtccgg agtgtacgac
tttctgctag gcagaggtca 1020taagctctga aatccatcgg gcggaggtgg
10501841050DNAHomo sapiens 184ccacctccgc ccgatggatt
tcagagctta tgacctctgc ctagcagaaa gtcgtacact 60ccggacccaa ggctgcaaca
aaagcgactg cgacgccgat actgaaatgg gctagacaaa 120ggaaagtgga accgtgcaga
gggaatcggc cgtggaaggg gctgtgtggt ccccacaagc 180tccgaaatta aacaagacgc
agttccccac ctcagacctg gagagggttc agtactggac 240ccctggcacc caccccacct
tccccggcct cctccgccac acctacagcg cctcgcctcc 300aggactcagc tttttcgacc
ctgtgtaatt ccaacctcca ggtgggcgcg ccccgaggcc 360gctccgagag cctcaggtgc
gaaagttaag ccgcggccgc gtcacctgag gcccgccggg 420cgagaggcgg ccaggccagc
ggcaacccta gcccagcccc ttggcacgtc cccgcctggg 480ccaacgtggg ggcccgggcc
accgcggctg ggtagggccc ggccgaggcc aggtccctcc 540gagaggcgcc gccgccgcgc
cccgcccgac tccgacccgc cggcctttac ctgtatccac 600gtcccggagc ctccggcttc
gcgccccgtc ccggcgctcc cggccgccag cagccaggct 660ctgaggactc gctgcggctc
cggcggcggc gatgccggtt cggcgagacg ggaagcgaca 720ggagccaaac cccgcggaaa
gcgctcgagc tgtgcctgca gccccgaccc cgcggcctcg 780gacgtggcgc cccggcgctc
gcccgccaca gccagcggcc ctgctcgccc cacgtctgcg 840ggttcccacc cgagccgcgc
gtgggcggcg ccgggctttg accccgcgca ggcagacaag 900cgccgcgggc cagacggaac
cgtgggaaag tttttctccc ttgtcatccc cttaccagag 960ccacagaaat tatccctgtg
gtctcccttg tcctcactcg gccttttctg gagttaagag 1020atccaagcca actactgggt
ctgttccctg 10501851800DNAHomo sapiens
185ggcagcagcc gctggcttct gcgcccacta ggagcttcgg atgcccgagt tagggctgcg
60ccaaggcggc cggagcagag agggagacgg ggacggggac aggcagggac aaagtgcaag
120aggcaaaact ggctgaaaag cagaagtgta ggagccgcca aggggcggga cgaacaggtc
180cgtgggccgg gcggagccaa gggtgggggc cggggtccct ccaggtggca ctcgcggcgc
240tagtccccag cctcctccct tcccccggcc ctgattggca ggcggcctgc gaccagccgc
300gaacgccaca gcgccccggg cgcccaggag aacgcgaacg gccccccgcg ggagcgggcg
360agtaggaggg ggcgccgggc tatatatata gcggctcggc ctcgggcggg cctggcgctc
420agggaggcgc gcactgctcc tcagagtccc agctccagcc gcgcgctttc cgcccggctc
480gccgctccat gcagccgggg tagagcccgg cgcccggggg ccccgtcgct tgcctcccgc
540acctcctcgg ttgcgcactc ctgcccgagg tcggccgtgc gctcccgcgg gacgccacag
600gcgcagctct gccccccagc ttcccgggcg cactgaccgc ctgaccgacg cacggccctc
660gggccgggat gtcggggccc gggacggccg cggtagcgct gctcccggcg gtcctgctgg
720ccttgctggc gccctgggcg ggccgagggg gcgccgccgc acccactgca cccaacggca
780cgctggaggc cgagctggag cgccgctggg agagcctggt ggcgctctcg ttggcgcgcc
840tgccggtggc agcgcagccc aaggaggcgg ccgtccagag cggcgccggc gactacctgc
900tgggcatcaa gcggctgcgg cggctctact gcaacgtggg catcggcttc cacctccagg
960cgctccccga cggccgcatc ggcggcgcgc acgcggacac ccgcgacagt gagtggcgcg
1020gccaggcgcg aaggggcggg ggcggggggc aacggccgcc gggccaaccc gctcagtcac
1080actctgagac cctcggcggg cacctgctcg ggggccccgg gaaccggggc ggactcgggc
1140tccggtccct tctgacgcgg ggctggggac gcagacactc ttggctccgg cagcccagcg
1200caacccctga ggtcgggcgc cgcctcccgc cttcagaaac tcgggctccg agcgccgaat
1260tccagcgcct tcgcccgtgg gcacagggcg cgcggtgcag ccacaggggg cccgagacac
1320gcgccccggc ctggcccagg ctggggaacc gctggggtcg ggctcgcgtc tgaaggtccg
1380ggactgggtg cggccgccgg gggtccccta cacaggcaag ctaatctgag ctagcgcagg
1440cttgggctcc ggaggcccta gagggcagct tgggctctgg aggcccttgg gggcggctgc
1500gccgggaacc ctggcccttt atccccaacc ccaccccaga aatagggtcc ccggaggcga
1560acaagccgag gggcggagtg ggccagggat cacctgcccc gcaatgacct gcgccccgcc
1620cccaggcctg ctggagctct cgcccgtgga gcggggcgtg gtgagcatct tcggcgtggc
1680cagccggttc ttcgtggcca tgagcagcaa gggcaagctc tatggctcgg tgagtaccgc
1740aggggtctgg ctaggcacct agttgggaac agcggacatg gctagcaggc tcgtggcttc
18001861800DNAHomo sapiens 186gaagccacga gcctgctagc catgtccgct gttcccaact
aggtgcctag ccagacccct 60gcggtactca ccgagccata gagcttgccc ttgctgctca
tggccacgaa gaaccggctg 120gccacgccga agatgctcac cacgccccgc tccacgggcg
agagctccag caggcctggg 180ggcggggcgc aggtcattgc ggggcaggtg atccctggcc
cactccgccc ctcggcttgt 240tcgcctccgg ggaccctatt tctggggtgg ggttggggat
aaagggccag ggttcccggc 300gcagccgccc ccaagggcct ccagagccca agctgccctc
tagggcctcc ggagcccaag 360cctgcgctag ctcagattag cttgcctgtg taggggaccc
ccggcggccg cacccagtcc 420cggaccttca gacgcgagcc cgaccccagc ggttccccag
cctgggccag gccggggcgc 480gtgtctcggg ccccctgtgg ctgcaccgcg cgccctgtgc
ccacgggcga aggcgctgga 540attcggcgct cggagcccga gtttctgaag gcgggaggcg
gcgcccgacc tcaggggttg 600cgctgggctg ccggagccaa gagtgtctgc gtccccagcc
ccgcgtcaga agggaccgga 660gcccgagtcc gccccggttc ccggggcccc cgagcaggtg
cccgccgagg gtctcagagt 720gtgactgagc gggttggccc ggcggccgtt gccccccgcc
cccgcccctt cgcgcctggc 780cgcgccactc actgtcgcgg gtgtccgcgt gcgcgccgcc
gatgcggccg tcggggagcg 840cctggaggtg gaagccgatg cccacgttgc agtagagccg
ccgcagccgc ttgatgccca 900gcaggtagtc gccggcgccg ctctggacgg ccgcctcctt
gggctgcgct gccaccggca 960ggcgcgccaa cgagagcgcc accaggctct cccagcggcg
ctccagctcg gcctccagcg 1020tgccgttggg tgcagtgggt gcggcggcgc cccctcggcc
cgcccagggc gccagcaagg 1080ccagcaggac cgccgggagc agcgctaccg cggccgtccc
gggccccgac atcccggccc 1140gagggccgtg cgtcggtcag gcggtcagtg cgcccgggaa
gctggggggc agagctgcgc 1200ctgtggcgtc ccgcgggagc gcacggccga cctcgggcag
gagtgcgcaa ccgaggaggt 1260gcgggaggca agcgacgggg cccccgggcg ccgggctcta
ccccggctgc atggagcggc 1320gagccgggcg gaaagcgcgc ggctggagct gggactctga
ggagcagtgc gcgcctccct 1380gagcgccagg cccgcccgag gccgagccgc tatatatata
gcccggcgcc ccctcctact 1440cgcccgctcc cgcggggggc cgttcgcgtt ctcctgggcg
cccggggcgc tgtggcgttc 1500gcggctggtc gcaggccgcc tgccaatcag ggccggggga
agggaggagg ctggggacta 1560gcgccgcgag tgccacctgg agggaccccg gcccccaccc
ttggctccgc ccggcccacg 1620gacctgttcg tcccgcccct tggcggctcc tacacttctg
cttttcagcc agttttgcct 1680cttgcacttt gtccctgcct gtccccgtcc ccgtctccct
ctctgctccg gccgccttgg 1740cgcagcccta actcgggcat ccgaagctcc tagtgggcgc
agaagccagc ggctgctgcc 18001871300DNAHomo sapiens 187tgaggtgagg
ggccggagga gcaagggaca agaggagcag aggacaggtg atggaaatcc 60tgcagcttta
ggctccattc tgccatctac atcccagcgc agggtgaagc ctgagagccc 120aaatggccaa
ctccacaggg ctgaacgcct cagaagtcgc aggctcgttg gggttgatcc 180tggcagctgt
cgtggaggtg ggggcactgc tgggcaacgg cgcgctgctg gtcgtggtgc 240tgcgcacgcc
gggactgcgc gacgcgctct acctggcgca cctgtgcgtc gtggacctgc 300tggcggccgc
ctccatcatg ccgctgggcc tgctggccgc accgccgccc gggctgggcc 360gcgtgcgcct
gggccccgcg ccatgccgcg ccgctcgctt cctctccgcc gctctgctgc 420cggcctgcac
gctcggggtg gccgcacttg gcctggcacg ctaccgcctc atcgtgcacc 480cgctgcggcc
aggctcgcgg ccgccgcctg tgctcgtgct caccgccgtg tgggccgcgg 540cgggactgct
gggcgcgctc tccctgctcg gcacgccgcc cgcaccgccc cctgctcctg 600ctcgctgctc
ggtcctggct gggggcctcg ggcccttccg gccgctctgg gccctgctgg 660ccttcgcgct
gcccgccctc ctgctgctcg gcgcctacgg cggcatcttc gtggtggcgc 720gtcgcgctgc
cctgaggccc ccacggccgg cgcgcgggtc ccgactccac tcggactctc 780tggatagccg
cctttccatc ttgccgccgc tccggcctcg cctgcccggg ggcaaggcgg 840ccctggcccc
agcgctggcc gtgggccaat ttgcagcctg ctggctgcct tatggctgcg 900cgtgcctggc
gcccgcagcg cgggccgcgg aagccgaagc ggctgtcacc tgggtcgcct 960actcggcctt
cgcggctcac cccttcctgt acgggctgct gcagcgcccc gtgcgcttgg 1020cactgggccg
cctctctcgc cgtgcactgc ctggacctgt gcgggcctgc actccgcaag 1080cctggcaccc
gcgggcactc ttgcaatgcc tccagagacc cccagagggc cctgccgtag 1140gcccttctga
ggctccagaa cagacccccg agttggcagg agggcggagc cccgcatacc 1200aggggccacc
tgagagttct ctctcctgag caggagaaag gagggtggtt tccgtggggg 1260ctcatccaac
ccctgcacag gtcacagcag gtgccctgct
13001881300DNAHomo sapiens 188agcagggcac ctgctgtgac ctgtgcaggg gttggatgag
cccccacgga aaccaccctc 60ctttctcctg ctcaggagag agaactctca ggtggcccct
ggtatgcggg gctccgccct 120cctgccaact cgggggtctg ttctggagcc tcagaagggc
ctacggcagg gccctctggg 180ggtctctgga ggcattgcaa gagtgcccgc gggtgccagg
cttgcggagt gcaggcccgc 240acaggtccag gcagtgcacg gcgagagagg cggcccagtg
ccaagcgcac ggggcgctgc 300agcagcccgt acaggaaggg gtgagccgcg aaggccgagt
aggcgaccca ggtgacagcc 360gcttcggctt ccgcggcccg cgctgcgggc gccaggcacg
cgcagccata aggcagccag 420caggctgcaa attggcccac ggccagcgct ggggccaggg
ccgccttgcc cccgggcagg 480cgaggccgga gcggcggcaa gatggaaagg cggctatcca
gagagtccga gtggagtcgg 540gacccgcgcg ccggccgtgg gggcctcagg gcagcgcgac
gcgccaccac gaagatgccg 600ccgtaggcgc cgagcagcag gagggcgggc agcgcgaagg
ccagcagggc ccagagcggc 660cggaagggcc cgaggccccc agccaggacc gagcagcgag
caggagcagg gggcggtgcg 720ggcggcgtgc cgagcaggga gagcgcgccc agcagtcccg
ccgcggccca cacggcggtg 780agcacgagca caggcggcgg ccgcgagcct ggccgcagcg
ggtgcacgat gaggcggtag 840cgtgccaggc caagtgcggc caccccgagc gtgcaggccg
gcagcagagc ggcggagagg 900aagcgagcgg cgcggcatgg cgcggggccc aggcgcacgc
ggcccagccc gggcggcggt 960gcggccagca ggcccagcgg catgatggag gcggccgcca
gcaggtccac gacgcacagg 1020tgcgccaggt agagcgcgtc gcgcagtccc ggcgtgcgca
gcaccacgac cagcagcgcg 1080ccgttgccca gcagtgcccc cacctccacg acagctgcca
ggatcaaccc caacgagcct 1140gcgacttctg aggcgttcag ccctgtggag ttggccattt
gggctctcag gcttcaccct 1200gcgctgggat gtagatggca gaatggagcc taaagctgca
ggatttccat cacctgtcct 1260ctgctcctct tgtcccttgc tcctccggcc cctcacctca
1300189800DNAHomo sapiens 189ccgcgacctt cgagaacccg
catgctgttc tccaccaggt ctctcagtcc tccctgcccc 60aatccccatg cccgcctccg
cgaccctgtg atgcctccct tcttgcacag gagcagtgac 120ctcagcactt acttaatcct
ctcccggcgc cgagctcagt tggagaggct aggggtggta 180gtgactggca ggaggccggg
gcggggggaa cccccaagcc cggcgtctgg ggctgcgggt 240ccgacccgag atccgccctc
cctgcaagcc ccgagccgct ggccaggccc gctactgcgc 300accagccgca tccgcgagcg
ctggctctgc cggcctgagc tagggtgggt agggccggga 360cccacggcgg aggtggggcc
gggccgagca gcctcggggg atccccgaag ctacagcgcc 420ttgcctccct gcacgctccg
cgcccccggc ctccgattgg ctgtcgggcc tagagcccgc 480ccagaattgg accgttcgct
tgtcgctcgg gtctggctcc acccccagag ggagcctaga 540acctggtcgc agtttttaga
gactaccctc accccgtggc ctgcgccgaa gttgggcgga 600ggacagtggg tggccaggcc
cttccgggcc agaactcggg acccctgcca gctacccgtg 660ccaggacaga ctcaagcccc
caaaacgcgg atggatgtac agaggagact tggggagagc 720actggactgg gagtccttgg
gcctgcactg aactctggct gactttgtga ccttgaagaa 780actgcttttc ccttcctgaa
800190800DNAHomo sapiens
190ttcaggaagg gaaaagcagt ttcttcaagg tcacaaagtc agccagagtt cagtgcaggc
60ccaaggactc ccagtccagt gctctcccca agtctcctct gtacatccat ccgcgttttg
120ggggcttgag tctgtcctgg cacgggtagc tggcaggggt cccgagttct ggcccggaag
180ggcctggcca cccactgtcc tccgcccaac ttcggcgcag gccacggggt gagggtagtc
240tctaaaaact gcgaccaggt tctaggctcc ctctgggggt ggagccagac ccgagcgaca
300agcgaacggt ccaattctgg gcgggctcta ggcccgacag ccaatcggag gccgggggcg
360cggagcgtgc agggaggcaa ggcgctgtag cttcggggat cccccgaggc tgctcggccc
420ggccccacct ccgccgtggg tcccggccct acccacccta gctcaggccg gcagagccag
480cgctcgcgga tgcggctggt gcgcagtagc gggcctggcc agcggctcgg ggcttgcagg
540gagggcggat ctcgggtcgg acccgcagcc ccagacgccg ggcttggggg ttccccccgc
600cccggcctcc tgccagtcac taccacccct agcctctcca actgagctcg gcgccgggag
660aggattaagt aagtgctgag gtcactgctc ctgtgcaaga agggaggcat cacagggtcg
720cggaggcggg catggggatt ggggcaggga ggactgagag acctggtgga gaacagcatg
780cgggttctcg aaggtcgcgg
8001911050DNAHomo sapiens 191ctgcagcagg acgtaagcac agtcatcgct gcaaactgca
aactcgtaag cacagtcatc 60gctgcaaact gcaaactcgt gctccgagcg ctgccctccc
ctgtggagcg gaggagggga 120ggcctggggc cgcggcggtg tgcgccccgc tctgaccgca
gagccccctt cccgaggaaa 180gcggctggcc cggtcccggc tggtgatcac gcggggcccc
tgtctgcttg gtgcgcaggt 240gagggtctgc ccttccgctg cgccccggac agcctggagg
tgagcacgcg ctgggccctg 300gaccgcgagc agcgggagaa gtacgagctg gtggccgtgt
gcaccgtgca cgccggcgcg 360cgcgaggagg tggtgatggt gcccttcccg gtgaccgtgt
acgacgagga cgactcggcg 420cccaccttcc ccgcgggcgt cgacaccgcc agcgccgtgg
tggagttcaa gcggaaggag 480gtgcttgtcc gcgcgtgctg tggtctaccc agtgtctgtc
tccggccaca gttcgtttct 540cggtcggttt agtgtccgtg tagccaccca accgtgtggc
cgaccattcg cgctttcatt 600tgtccttcgc ctccgtctgc gccgtctgtc ctagggggag
gggaaggggg agtcctgcca 660gcacccagct gggccttgcc tcgggaggca aggaccagga
cgaggcccga gggctcgcgt 720ctggggcata cttgtgccgc tgcaggcggg cgcggcgcgc
tgcccgggcg gggagcatct 780gccgggaggg cactccctcc caccagcagt tagcccccaa
cgggagggcc cttgagtgac 840cacgagcaga gccggggatt ggagaaggac gggaaggcgg
atcacctccg gcgccgcccg 900ccccgccctt ctccggctcg cgctggtgga gcgcgaccgc
cacctgctgg gcctcggcct 960tcctgcagcc ggcccaccca gcaggggccg tgggagagtg
ggcgtgggga ctgaggtagg 1020tagtacgttg ccttgttccg cttctctggg
10501921050DNAHomo sapiens 192cccagagaag cggaacaagg
caacgtacta cctacctcag tccccacgcc cactctccca 60cggcccctgc tgggtgggcc
ggctgcagga aggccgaggc ccagcaggtg gcggtcgcgc 120tccaccagcg cgagccggag
aagggcgggg cgggcggcgc cggaggtgat ccgccttccc 180gtccttctcc aatccccggc
tctgctcgtg gtcactcaag ggccctcccg ttgggggcta 240actgctggtg ggagggagtg
ccctcccggc agatgctccc cgcccgggca gcgcgccgcg 300cccgcctgca gcggcacaag
tatgccccag acgcgagccc tcgggcctcg tcctggtcct 360tgcctcccga ggcaaggccc
agctgggtgc tggcaggact cccccttccc ctccccctag 420gacagacggc gcagacggag
gcgaaggaca aatgaaagcg cgaatggtcg gccacacggt 480tgggtggcta cacggacact
aaaccgaccg agaaacgaac tgtggccgga gacagacact 540gggtagacca cagcacgcgc
ggacaagcac ctccttccgc ttgaactcca ccacggcgct 600ggcggtgtcg acgcccgcgg
ggaaggtggg cgccgagtcg tcctcgtcgt acacggtcac 660cgggaagggc accatcacca
cctcctcgcg cgcgccggcg tgcacggtgc acacggccac 720cagctcgtac ttctcccgct
gctcgcggtc cagggcccag cgcgtgctca cctccaggct 780gtccggggcg cagcggaagg
gcagaccctc acctgcgcac caagcagaca ggggccccgc 840gtgatcacca gccgggaccg
ggccagccgc tttcctcggg aagggggctc tgcggtcaga 900gcggggcgca caccgccgcg
gccccaggcc tcccctcctc cgctccacag gggagggcag 960cgctcggagc acgagtttgc
agtttgcagc gatgactgtg cttacgagtt tgcagtttgc 1020agcgatgact gtgcttacgt
cctgctgcag 1050193800DNAHomo sapiens
193gcgccgacgg gggcgggtgg taggggatgt acgggtgtgt atatgcagag gtatgccagg
60ctctgcccct taaagtttgg gggccggcgg aggcggcgcc gtggccggga gaaagtgtct
120ctcatttagg agggtttgca ggtccagagt aaagtcactg aagagtggaa gcgaggaagg
180aacaggatga ttagacctca gctgcggacc gcggggctgg gacgatgcct cctgccgggg
240ctgctgctgc tcctggtgcc cgtcctctgg gccggggctg aaaagctaca tacccagccc
300tcctgccccg cggtctgcca gcccacgcgc tgccccgcgc tgcccacctg cgcgctgggg
360accacgccgg tgttcgacct gtgccgctgt tgccgcgtct gccccgcggc cgagcgtgaa
420gtctgcggcg gggcgcaggg ccaaccgtgc gccccggggc tgcagtgcct ccagccgctg
480cgccccgggt tccccagcac ctgcggttgc ccgacgctgg gaggggccgt gtgcggcagc
540gacaggcgca cctaccccag catgtgcgcg ctccgggccg aaaaccgcgc cgcgcgccgc
600ctgggcaagg tcccggccgt gcctgtgcag tgggggaact gcggggatac aggtgagccg
660cgggggcgcg cgccctcgga acactttcta actctggagg agcgtaaagg aacaagacct
720cactgagacc gcacagttcg cgcctggtcc tcctgcgtca tttgcctcct ggattcgaca
780cctctgtgtt cctgatttcc
800194800DNAHomo sapiens 194ggaaatcagg aacacagagg tgtcgaatcc aggaggcaaa
tgacgcagga ggaccaggcg 60cgaactgtgc ggtctcagtg aggtcttgtt cctttacgct
cctccagagt tagaaagtgt 120tccgagggcg cgcgcccccg cggctcacct gtatccccgc
agttccccca ctgcacaggc 180acggccggga ccttgcccag gcggcgcgcg gcgcggtttt
cggcccggag cgcgcacatg 240ctggggtagg tgcgcctgtc gctgccgcac acggcccctc
ccagcgtcgg gcaaccgcag 300gtgctgggga acccggggcg cagcggctgg aggcactgca
gccccggggc gcacggttgg 360ccctgcgccc cgccgcagac ttcacgctcg gccgcggggc
agacgcggca acagcggcac 420aggtcgaaca ccggcgtggt ccccagcgcg caggtgggca
gcgcggggca gcgcgtgggc 480tggcagaccg cggggcagga gggctgggta tgtagctttt
cagccccggc ccagaggacg 540ggcaccagga gcagcagcag ccccggcagg aggcatcgtc
ccagccccgc ggtccgcagc 600tgaggtctaa tcatcctgtt ccttcctcgc ttccactctt
cagtgacttt actctggacc 660tgcaaaccct cctaaatgag agacactttc tcccggccac
ggcgccgcct ccgccggccc 720ccaaacttta aggggcagag cctggcatac ctctgcatat
acacacccgt acatccccta 780ccacccgccc ccgtcggcgc
800195801DNAHomo sapiens 195ttgtcttctc ccttccgacc
tcccgtggcc ccagcgcggc cagctcacag taggtgctcg 60ggcagcgttt cttcagggac
ctagacggcc tggagaggaa gggccccagc ccagccgccc 120gggcctctca cctggctctc
ggggcgcccg gctcgcactt cctcccgccg ccccgcccct 180tccacattcc tgccccgccg
ggcctgcccc gcgcagtctg ggtctctgcg ccgcagccgc 240ccgcccgccc gctcagcgcc
cggccccggg atgacggcgg cccaggccgc gggtgaggag 300gcgccaccag gcgtgcggtc
cgtcaaggtg gtcctggtgg gcgacggcgg ctgcgggaag 360acgtcgctgc tgatggtctt
cgccgatggg gccttccccg aggtgagtgc cccgcgcctc 420cgcctcgccc ggttccgctc
gcgcgcccgg gtgtacaggt ccgtgccgga gcggcccagg 480ctgtgcgcct aacccggcct
ccgaggggtg tcccagcggg gcctggggtc cagggcagag 540ttcttccgcc ccagccattg
ggaatgaagg cctcagtgat gttatctgta aagccggagg 600aatggcatcc accggggaga
ggtgtcacaa ggactgagtg aggcgacctg ggtgcacaca 660agatcctaag acagcacttg
gccacacaat tccgctgagg gcctgagagc ttggaagcca 720gactgccgag gttcaaatta
tggctttgcc tcttatagct gtgtgccctt gggtaagtcc 780cctaaccctg ctgtgcctgt g
8011961301DNAHomo sapiens
196attgagagag agggagggcg aaaggaagga aggggagcca gaggtgggag tggaagaggc
60agcctcgcct ggggctgatt ggctcccgag gccagggctc tccaagcggt ttataagagt
120tggggctgcc gggcgccctg cccgctcgcc cgcgcgcccc aggacccaaa gccgggctcc
180aagtcggcgc cccacgtcga ggctccgccg cagcctccgg agttggccgc agacaagaag
240gggagggagc gggagaggga ggagagctcc gaagcgagag ggccgagcgc catgcgccgc
300gccagcagag actacaccaa gtacctgcgt ggctcggagg agatgggcgg cggccccgga
360gccccgcacg agggccccct gcacgccccg ccgccgcctg cgccgcacca gccccctgcc
420gcctcccgct ccatgttcgt ggccctcctg gggctggggc tgggccaggt tgtctgcagc
480gtcgccctgt tcttctattt cagagcgcag gtgagtggcc accttcccag gggatcgcgg
540ctgagagcgc ccatctcctt cccccgcact tggaaactga gtctggcggc agggctgggc
600cacccagagc ttgcatattc cggaagggaa agtgactcca gaagggagag aggaagtgtt
660gagtttgggg acaacctggc gcagggctgt cgggcgcacc ctgctctctc tccgcccacg
720caccccagct tctcggtgct ctgggggcgg actcccctgg ccggacgatg ggtttgaatc
780tcaccccgtc ccttcgctgg gaaacaacac tggcctctca ccttttctgg tagtgattgc
840atactttttc tccctgtcat ttctcacttg aagttaagaa tcaacttctg ttcacgtagg
900aaaaaagatg agcgccttca cttgggcatc tacctttccc ttcccgccca ccacccggcg
960ggtttcggtt cctgcgcctg gctgctctgc aggtgtgctg gggccacggt gctggagggc
1020tgcgcggagc gggaggtcgc ggtgctcgtg cccaggtcgc ccaatgggtg ggcagaatga
1080cacggcgcga ccagagaggc gcgggctcgg gatgggggct ctgcggctgt ggcgctgtcc
1140tgtgggggtg aaggaagagg gacagcccca cgtgcctgct agggatgtgg gcggaggaag
1200gaagcgaggt gagtgtgatg gcacagtgtt actacagtct agcaaataac caaccttcgg
1260aaagatgaag aggttttttg cacgacggct aggaactgca g
13011974301DNAHomo sapiens 197gcaatttata gatgagagcg tggacggcag agagcattgt
gtatgttgaa gtctctgcga 60tatggggtgt ccctgctgcc ccgctccagc ctttcacttc
tgacctcctt cctctggctc 120ttacgctaca ggatccaaaa ctactcggaa gacttgccgc
gggcggtgat tgacgacgcc 180tttgcccgcg ccttcgcact gtggagcgcg gtgacgccgc
tcaccttcac tcgcgtgtac 240agccgggacg cagacatcgt catccagttt ggtgtcgcgg
gtgagaacgt gaggagggaa 300aatccaagag acctgggcgg ggtcagggaa gggaggacca
cggagagcgt ggaggcagca 360gtggccccgg cttcctcttg cctgcccgcg ctgccctggc
ttatacggcc cctcctgcca 420gacagtgcac agggccaggg cgccaggctg ggagagcttc
gcgcaggcgg gatttcagcc 480cgcacttatt tcggagccct tgccttgggc agcgcacaat
ctgcgcagca gtactcggct 540aaccctcttc ctctcgacct gtttcttcag agcacggaga
cgggtatccc ttcgacggga 600aggacgggct cctggcacac gcctttcctc ctggccccgg
cattcaggga gacgcccatt 660tcgacgatga cgagttgtgg tccctgggca agggcgtcgg
tgagattctg agtcctcctg 720gcccctgatt cccttcattc tctcccactc atcacccgcc
gccctaactc cggtcccccc 780tcctcctgca gtggttccaa ctcggtttgg aaacgcagat
ggcgcggcct gccacttccc 840cttcatcttc gagggccgct cctactctgc ctgcaccacc
gacggtcgct ccgacggctt 900gccctggtgc agtaccacgg ccaactacga caccgacgac
cggtttggct tctgccccag 960cgagagtgag tgagggggct cgccgagggc tgggggcgcc
caccaccctt gatggtcctg 1020ggttctaatt ccagctctgc cactagtgct gtgtggcctg
caattcaccc tcccgcactc 1080tgggcccaat tttctcatct gagaaatgat gagagatggg
atgaactgca gaccatccat 1140gggtcaaaga acaggacaca cttgggggtt ataatgtgct
gtctccgcct tctccccctt 1200tcccacatcc tcctcgcccc aggactctac acccaggacg
gcaatgctga tgggaaaccc 1260tgccagtttc cattcatctt ccaaggccaa tcctactccg
cctgcaccac ggacggtcgc 1320tccgacggct accgctggtg cgccaccacc gccaactacg
accgggacaa gctcttcggc 1380ttctgcccga cccgaggtac ctccaccctg tctaccaggt
tcagccccgc cctctcatca 1440tgtattggcc cccaaaacgc ggctcttccc tcccatcagt
ttgtctttcc actctcattg 1500gtcctcagga cgaccgtgac tccgcccacc tacaccacat
ttccaccact atccctgact 1560tccaatggcc ccgccccagc cactaaggtt cggccttttc
tgcccagctg gccgcctctt 1620ccttggtctg gtgtcccagg caccgcccac gggtctagcc
tcttctcagg agtgctctac 1680agcgccccct aggccaccaa gattgtttag ctccctgtcg
ggtcggcccc tgactcctta 1740ttggactcat ccatctggct catccaaggc cttgggtctc
tccagctgac tcgacggtga 1800tggggggcaa ctcggcgggg gagctgtgcg tcttcccctt
cactttcctg ggtaaggagt 1860actcgacctg taccagcgag ggccgcggag atgggcgcct
ctggtgcgct accacctcga 1920actttgacag cgacaagaag tggggcttct gcccggacca
aggtaggcgt ggtcccgcgg 1980ctccggggct ggggttcccg gcagtggtgg tggtggggtg
gccagggctg ggggctcggc 2040ccggcgctca cgtctcaggc tccctctccc tccaggatac
agtttgttcc tcgtggcggc 2100gcatgagttc ggccacgcgc tgggcttaga tcattcctca
gtgccggagg cgctcatgta 2160ccctatgtac cgcttcactg aggggccccc cttgcataag
gacgacgtga atggcatccg 2220gcacctctat ggtgaggcag gggcagggat gggaggagga
ggggaaaggg cgtggctgtg 2280ccacagtacc aaagaattgg gggttgggga tcgggggagg
aacggggcgt gcaggagagg 2340tgggacctca acgtctgtct ggaagcagag cctgggccca
gtcgctgcca tgtcagtgct 2400tagaggtggt gataaagaga ctctagagag agataggtgt
gacttcaaaa gccagtctac 2460tctgggcatg gtggctcacg cctctaatcc cagggctttg
ggagacccaa ggcgggagga 2520ttgcttaagc ccaggagttc cagaccagcc tcggcaacat
agccagactc ccatctctac 2580aaaaaataaa tgagcaaggc gtgaaggcac atgtctgtag
tcctagctac tctggaggct 2640gaggtgggag gatctcttga gcccaggagt tcgaggctgt
agtgagctat gattgcacca 2700ctgcattcca tcctgggcca tagaggatgt cgcttaaaac
gaaaaagaag aagaagaaag 2760tcctgtggtt tgggaaggga ggctgagtga ggaggggcct
gtgtgccaga ggaggcttca 2820ctgagaagct taggggagca gatgttctag gggtacagag
gtatgcagga ataggaagag 2880tctcaccccg tgtctctttt taggtcctcg ccctgaacct
gagccacggc ctccaaccac 2940caccacaccg cagcccacgg ctcccccgac ggtctgcccc
accggacccc ccactgtcca 3000cccctcagag cgccccacag ctggccccac aggtcccccc
tcagctggcc ccacaggtcc 3060ccccactgct ggcccttcta cggccactac tgtgcctttg
agtccggtgg acgatgcctg 3120caacgtgaac atcttcgacg ccatcgcgga gattgggaac
cagctgtatt tgttcaagga 3180tgggtgagga ggcggggttg tgtggatgcg ggagggggct
ttgcggaggg gctgcccgtc 3240ccttcccgcc cactggccct gtgtccaagg cttagagccc
gtcctttccc tcctcgcttt 3300ctcaggaagt actggcgatt ctctgagggc agggggagcc
ggccgcaggg ccccttcctt 3360atcgccgaca agtggcccgc gctgccccgc aagctggact
cggtctttga ggagcggctc 3420tccaagaagc ttttcttctt ctctggttag ttacctactt
tccctccccc gcccggtcaa 3480tccccatcag tcaaggaggc tcaagagacc atcgataacc
cacgaaacgt cttgtgcgtt 3540ttagaaaaat acgccccctg gcggacgcag tttagcaaac
gtaggggcgg ctgagtttct 3600gccccctcct ctccacgccc tcgcgtcgct ctacccagcg
cctctgcccc tgggttgcag 3660ggactgcggg cacgcgggct aggaaaggcc tcgccggaat
ctccctcctc gcgttctagg 3720agtacgtgct ccctctgcgc ccccaaaccg acgtgaccct
cctcccctgc agggcgccag 3780gtgtgggtgt acacaggcgc gtcggtgctg ggcccgaggc
gtctggacaa gctgggcctg 3840ggagccgacg tggcccaggt gaccggggcc ctccggagtg
gcagggggaa gatgctgctg 3900ttcagcgggc ggcgcctctg gaggtgagcg ccgccgcggc
cgccggcagg gggagcccgg 3960gcgccgtcgg tccgtccgct agccggctca gcacctgtct
cctccgcgcc tgcccgcagg 4020ttcgacgtga aggcgcagat ggtggatccc cggagcgcca
gcgaggtgga ccggatgttc 4080cccggggtgc ctttggacac gcacgacgtc ttccagtacc
gaggtgaggg ctgaggagga 4140tcccttcgtg agacaccaca ctaagctcct cttagtgagt
ggtcaaattc tgagcgagga 4200agaaaaagcc cttggaaatg gaaacaaatg ccccagcaca
gacaagatcc cagcagaggc 4260agaggccttc tccaggtcat ttaggaagtc agggatgcaa c
4301198801DNAHomo sapiens 198caggaacttt cgagatgagg
tgcctttccc aaggtgacac taagtggagg agcccagcca 60gagtccaggg gtccttacac
aaccttcggt ggtctctctt tacctgtgaa gctgcagcct 120gcttcccagc tcgggggcgt
gtacaggaga ctggacctgg ggcagcctca gaatgcctgg 180ctgcctggag ctctcctcgc
gtgtccaggc ggcctgcttg gtctccctcc tctcccctct 240taggtgccgg ggcgggcacc
cggtgcaggg tgggcacggc gcctgccacc agcctcaggc 300gctgggagaa gcgcaggttc
ttctggataa ccgaagagac gtcaaaacag gctggggcaa 360agtggtcaga gcagatgacc
gagcggtcat tgcctccgta ccagtcggcg cggcaacccc 420gcacgaagcg gtcccagagc
agccgcacgg cccggtcctt gggaaagcgg aacagcgact 480tcccagactt ggtggtgttg
ccgcagtggg cggccacaca acgggccggc atggcggccg 540tcttcggtgc gcgggagccg
ggttccctgg accttcgccc ttgggcacgc tcctcgcagc 600ggcctcggcg aggcaagtcc
tcccctcctc acctgtccac tccgggtcgg gattgtttcc 660ttccctacct ctggtcaccg
gaagtggcga tctggggccc ccaatgggag ggctctttga 720tatcttcctc ctcctcctcc
ctgcgctgct ccccaggagc cagtggacac aagcagaggg 780atacaaattt cgcgcgggca g
80119924DNAArtificialPrimer
199tgatggtcgt attgcgggtt tatc
2420024DNAArtificialPrimer 200atacctaaac ccaacgccga ctac
2420124DNAArtificialPrimer 201cgcgatttga
gtagttagcg tcgt
2420224DNAArtificialPrimer 202aaccaacgcg acgacctaac taac
2420323DNAArtificialPrimer 203tagatttcgg
tgtttcgggc gtt
2320426DNAArtificialPrimer 204ccgctaattc ccaatcgtac tactca
2620522DNAArtificialPrimer 205ttcgtttcgt
tcggtcgtga tt
2220624DNAArtificialPrimer 206gactacgaac gcttcgaatt cctc
2420724DNAArtificialPrimer 207gttgcgttgg
tagcgattcg ttgt
2420823DNAArtificialPrimer 208cccgaaccga atcctcgaaa tct
2320925DNAArtificialPrimer 209gacgtagtat
gatgcgcgta gtgtg
2521023DNAArtificialPrimer 210gcgaacatac taaacccgaa ccc
2321124DNAArtificialPrimer 211ggattacgtc
ggtgttcgat ttgt
2421222DNAArtificialPrimer 212aacgcacgat taaccctacg cc
2221324DNAArtificialPrimer 213tcggattaag
gtaggcgtgg tttc
2421421DNAArtificialPrimer 214aacgtaaacg ccgaaccgaa c
2121524DNAArtificialPrimer 215ggaagacgtc
gttgttgatg gttt
2421623DNAArtificialPrimer 216accgctccga cacgaaccta tac
2321723DNAArtificialPrimer 217agcgttatgc
gtcgcgttag tag
2321822DNAArtificialPrimer 218gcaaacgacg acgaaacgta ca
2221923DNAArtificialPrimer 219gaagagagcg
ggttcgggat aag
2322023DNAArtificialPrimer 220ctacaacatc gtaaacgcgc gac
2322122DNAArtificialPrimer 221gagaagagga
aggtagaagg ag
2222221DNAArtificialPrimer 222ctacctaact ataaccaacc c
2122321DNAArtificialPrimer 223acggaggagg
atagtagtac g
2122426DNAArtificialPrimer 224aggtaygttg tatttggtgg atttgg
2622521DNAArtificialPrimer 225cccacctaca
acaacaacac c
2122620DNAArtificialPrimer 226gaacgcgtac ggaaggtagg
2022727DNAArtificialPrimer 227gtgataggtt
tgtagatttg atagttg
2722825DNAArtificialPrimer 228aactaacctc cattttaact atttc
2522923DNAArtificialPrimer 229gagagatgaa
tttggatatt agt
2323024DNAArtificialPrimer 230ggtaaattgg tgtygttgga gaag
2423123DNAArtificialPrimer 231actaaacaat
aatacccrac ctc
2323224DNAArtificialPrimer 232gtcgttgggt tcggtttcgt tttg
24
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