TW202309274A - 產生成熟角膜內皮細胞之方法 - Google Patents
產生成熟角膜內皮細胞之方法 Download PDFInfo
- Publication number
- TW202309274A TW202309274A TW111116689A TW111116689A TW202309274A TW 202309274 A TW202309274 A TW 202309274A TW 111116689 A TW111116689 A TW 111116689A TW 111116689 A TW111116689 A TW 111116689A TW 202309274 A TW202309274 A TW 202309274A
- Authority
- TW
- Taiwan
- Prior art keywords
- corneal endothelial
- amino acid
- seq
- cells
- expression
- Prior art date
Links
- 210000000399 corneal endothelial cell Anatomy 0.000 title claims abstract description 280
- 238000000034 method Methods 0.000 title claims abstract description 241
- 230000014509 gene expression Effects 0.000 claims abstract description 393
- 108091023040 Transcription factor Proteins 0.000 claims abstract description 288
- 102000040945 Transcription factor Human genes 0.000 claims abstract description 287
- 230000003511 endothelial effect Effects 0.000 claims abstract description 268
- 230000001965 increasing effect Effects 0.000 claims abstract description 243
- 210000000130 stem cell Anatomy 0.000 claims description 426
- 102100036090 Pituitary homeobox 2 Human genes 0.000 claims description 199
- 101000595669 Homo sapiens Pituitary homeobox 2 Proteins 0.000 claims description 196
- 102100025457 LIM homeobox transcription factor 1-beta Human genes 0.000 claims description 177
- 101000984044 Homo sapiens LIM homeobox transcription factor 1-beta Proteins 0.000 claims description 173
- 108090000623 proteins and genes Proteins 0.000 claims description 170
- 102000004893 Transcription factor AP-2 Human genes 0.000 claims description 169
- 108090001039 Transcription factor AP-2 Proteins 0.000 claims description 169
- 102100021084 Forkhead box protein C1 Human genes 0.000 claims description 159
- 101000818310 Homo sapiens Forkhead box protein C1 Proteins 0.000 claims description 159
- 101000738965 Homo sapiens POU domain, class 6, transcription factor 2 Proteins 0.000 claims description 151
- 102100037484 POU domain, class 6, transcription factor 2 Human genes 0.000 claims description 150
- 150000007523 nucleic acids Chemical class 0.000 claims description 105
- 239000013604 expression vector Substances 0.000 claims description 104
- 102000039446 nucleic acids Human genes 0.000 claims description 97
- 108020004707 nucleic acids Proteins 0.000 claims description 97
- 102000001708 Protein Isoforms Human genes 0.000 claims description 76
- 108010029485 Protein Isoforms Proteins 0.000 claims description 76
- 239000013598 vector Substances 0.000 claims description 68
- 230000001939 inductive effect Effects 0.000 claims description 61
- 125000003729 nucleotide group Chemical group 0.000 claims description 58
- 239000002773 nucleotide Substances 0.000 claims description 54
- 102000004169 proteins and genes Human genes 0.000 claims description 54
- 239000013603 viral vector Substances 0.000 claims description 53
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 52
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 51
- 108020004414 DNA Proteins 0.000 claims description 43
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 37
- 210000000933 neural crest Anatomy 0.000 claims description 37
- 108020004999 messenger RNA Proteins 0.000 claims description 30
- 102000016681 SLC4A Proteins Human genes 0.000 claims description 27
- 102100024337 Collagen alpha-1(VIII) chain Human genes 0.000 claims description 25
- 101000909492 Homo sapiens Collagen alpha-1(VIII) chain Proteins 0.000 claims description 25
- 208000024891 symptom Diseases 0.000 claims description 25
- 230000002103 transcriptional effect Effects 0.000 claims description 25
- 102100040496 Collagen alpha-2(VIII) chain Human genes 0.000 claims description 24
- 101000749886 Homo sapiens Collagen alpha-2(VIII) chain Proteins 0.000 claims description 24
- 238000012258 culturing Methods 0.000 claims description 20
- -1 RELA Proteins 0.000 claims description 19
- 238000005086 pumping Methods 0.000 claims description 19
- 238000002054 transplantation Methods 0.000 claims description 19
- 210000001578 tight junction Anatomy 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 230000001124 posttranscriptional effect Effects 0.000 claims description 17
- 101000986598 Homo sapiens Mas-related G-protein coupled receptor member X3 Proteins 0.000 claims description 16
- 102100028178 Mas-related G-protein coupled receptor member X3 Human genes 0.000 claims description 16
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 claims description 15
- 108010002321 Tight Junction Proteins Proteins 0.000 claims description 13
- 102000000591 Tight Junction Proteins Human genes 0.000 claims description 13
- 230000002829 reductive effect Effects 0.000 claims description 13
- 102000053602 DNA Human genes 0.000 claims description 12
- 239000003112 inhibitor Substances 0.000 claims description 11
- 239000002502 liposome Substances 0.000 claims description 10
- 101000664703 Homo sapiens Transcription factor SOX-10 Proteins 0.000 claims description 9
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 claims description 9
- 102100038808 Transcription factor SOX-10 Human genes 0.000 claims description 9
- 102100033725 Tumor necrosis factor receptor superfamily member 16 Human genes 0.000 claims description 9
- 241000700605 Viruses Species 0.000 claims description 9
- 230000036542 oxidative stress Effects 0.000 claims description 9
- 101150050047 BHLHE40 gene Proteins 0.000 claims description 7
- 102100034799 CCAAT/enhancer-binding protein delta Human genes 0.000 claims description 7
- 102100026191 Class E basic helix-loop-helix protein 40 Human genes 0.000 claims description 7
- 102100031127 Cysteine/serine-rich nuclear protein 1 Human genes 0.000 claims description 7
- 102100023226 Early growth response protein 1 Human genes 0.000 claims description 7
- 102100028121 Fos-related antigen 2 Human genes 0.000 claims description 7
- 101000945965 Homo sapiens CCAAT/enhancer-binding protein delta Proteins 0.000 claims description 7
- 101000922196 Homo sapiens Cysteine/serine-rich nuclear protein 1 Proteins 0.000 claims description 7
- 101001049697 Homo sapiens Early growth response protein 1 Proteins 0.000 claims description 7
- 101001059934 Homo sapiens Fos-related antigen 2 Proteins 0.000 claims description 7
- 101001006892 Homo sapiens Krueppel-like factor 10 Proteins 0.000 claims description 7
- 101001139112 Homo sapiens Krueppel-like factor 9 Proteins 0.000 claims description 7
- 101000978926 Homo sapiens Nuclear receptor subfamily 1 group D member 1 Proteins 0.000 claims description 7
- 101001109700 Homo sapiens Nuclear receptor subfamily 4 group A member 1 Proteins 0.000 claims description 7
- 101000931462 Homo sapiens Protein FosB Proteins 0.000 claims description 7
- 101000861454 Homo sapiens Protein c-Fos Proteins 0.000 claims description 7
- 101000851700 Homo sapiens Steroid hormone receptor ERR1 Proteins 0.000 claims description 7
- 101000596334 Homo sapiens TSC22 domain family protein 1 Proteins 0.000 claims description 7
- 102100027798 Krueppel-like factor 10 Human genes 0.000 claims description 7
- 102100020684 Krueppel-like factor 9 Human genes 0.000 claims description 7
- 102100023170 Nuclear receptor subfamily 1 group D member 1 Human genes 0.000 claims description 7
- 102100022679 Nuclear receptor subfamily 4 group A member 1 Human genes 0.000 claims description 7
- 102100020847 Protein FosB Human genes 0.000 claims description 7
- 102100027584 Protein c-Fos Human genes 0.000 claims description 7
- 102100036832 Steroid hormone receptor ERR1 Human genes 0.000 claims description 7
- 102100035051 TSC22 domain family protein 1 Human genes 0.000 claims description 7
- 238000003776 cleavage reaction Methods 0.000 claims description 7
- 230000006378 damage Effects 0.000 claims description 7
- 101001077417 Gallus gallus Potassium voltage-gated channel subfamily H member 6 Proteins 0.000 claims description 6
- 101000898093 Homo sapiens Protein C-ets-2 Proteins 0.000 claims description 6
- 101001028730 Homo sapiens Transcription factor JunB Proteins 0.000 claims description 6
- 101001050297 Homo sapiens Transcription factor JunD Proteins 0.000 claims description 6
- 101001010792 Homo sapiens Transcriptional regulator ERG Proteins 0.000 claims description 6
- 102100021890 Protein C-ets-2 Human genes 0.000 claims description 6
- 108020004682 Single-Stranded DNA Proteins 0.000 claims description 6
- 102100028509 Transcription factor IIIA Human genes 0.000 claims description 6
- 102100037168 Transcription factor JunB Human genes 0.000 claims description 6
- 102100023118 Transcription factor JunD Human genes 0.000 claims description 6
- 239000003102 growth factor Substances 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- 102100022933 ATM interactor Human genes 0.000 claims description 5
- 102100039958 BUB3-interacting and GLEBS motif-containing protein ZNF207 Human genes 0.000 claims description 5
- 208000002177 Cataract Diseases 0.000 claims description 5
- 102100023580 Cyclic AMP-dependent transcription factor ATF-4 Human genes 0.000 claims description 5
- 102100032082 Dr1-associated corepressor Human genes 0.000 claims description 5
- 102100035078 ETS-related transcription factor Elf-2 Human genes 0.000 claims description 5
- 102100031702 Endoplasmic reticulum membrane sensor NFE2L1 Human genes 0.000 claims description 5
- 102100023830 Homeobox protein EMX2 Human genes 0.000 claims description 5
- 101000902754 Homo sapiens ATM interactor Proteins 0.000 claims description 5
- 101000744928 Homo sapiens BUB3-interacting and GLEBS motif-containing protein ZNF207 Proteins 0.000 claims description 5
- 101000905743 Homo sapiens Cyclic AMP-dependent transcription factor ATF-4 Proteins 0.000 claims description 5
- 101000638315 Homo sapiens Dr1-associated corepressor Proteins 0.000 claims description 5
- 101000877377 Homo sapiens ETS-related transcription factor Elf-2 Proteins 0.000 claims description 5
- 101001048970 Homo sapiens Homeobox protein EMX2 Proteins 0.000 claims description 5
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 claims description 5
- 101000615495 Homo sapiens Methyl-CpG-binding domain protein 3 Proteins 0.000 claims description 5
- 101000979623 Homo sapiens Nucleoside diphosphate kinase B Proteins 0.000 claims description 5
- 101000572989 Homo sapiens POU domain, class 3, transcription factor 3 Proteins 0.000 claims description 5
- 101000983170 Homo sapiens Proliferation-associated protein 2G4 Proteins 0.000 claims description 5
- 101000671649 Homo sapiens Upstream stimulatory factor 2 Proteins 0.000 claims description 5
- 101000788753 Homo sapiens Zinc finger protein 358 Proteins 0.000 claims description 5
- 101000964713 Homo sapiens Zinc finger protein 395 Proteins 0.000 claims description 5
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 claims description 5
- 102100021291 Methyl-CpG-binding domain protein 3 Human genes 0.000 claims description 5
- 108010071380 NF-E2-Related Factor 1 Proteins 0.000 claims description 5
- 102100023258 Nucleoside diphosphate kinase B Human genes 0.000 claims description 5
- 108091034117 Oligonucleotide Proteins 0.000 claims description 5
- 102100026456 POU domain, class 3, transcription factor 3 Human genes 0.000 claims description 5
- 102100026899 Proliferation-associated protein 2G4 Human genes 0.000 claims description 5
- 108010029625 T-Box Domain Protein 2 Proteins 0.000 claims description 5
- 102100038721 T-box transcription factor TBX2 Human genes 0.000 claims description 5
- 102000004853 Transcription Factor DP1 Human genes 0.000 claims description 5
- 108090001097 Transcription Factor DP1 Proteins 0.000 claims description 5
- 108010068068 Transcription Factor TFIIIA Proteins 0.000 claims description 5
- 102100040103 Upstream stimulatory factor 2 Human genes 0.000 claims description 5
- 102000033021 YBX1 Human genes 0.000 claims description 5
- 108091002437 YBX1 Proteins 0.000 claims description 5
- 102100025431 Zinc finger protein 358 Human genes 0.000 claims description 5
- 102100040733 Zinc finger protein 395 Human genes 0.000 claims description 5
- 239000002105 nanoparticle Substances 0.000 claims description 5
- 210000002706 plastid Anatomy 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- 230000001177 retroviral effect Effects 0.000 claims description 5
- 238000001356 surgical procedure Methods 0.000 claims description 5
- 206010010356 Congenital anomaly Diseases 0.000 claims description 4
- 206010010996 Corneal degeneration Diseases 0.000 claims description 4
- 206010011033 Corneal oedema Diseases 0.000 claims description 4
- 208000003923 Hereditary Corneal Dystrophies Diseases 0.000 claims description 4
- 206010053678 Iridocorneal endothelial syndrome Diseases 0.000 claims description 4
- 241000711408 Murine respirovirus Species 0.000 claims description 4
- 201000004781 bullous keratopathy Diseases 0.000 claims description 4
- 201000004778 corneal edema Diseases 0.000 claims description 4
- 230000002463 transducing effect Effects 0.000 claims description 4
- 230000008733 trauma Effects 0.000 claims description 4
- 241000702421 Dependoparvovirus Species 0.000 claims description 3
- 201000001925 Fuchs' endothelial dystrophy Diseases 0.000 claims description 3
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 claims description 3
- 108010007568 Protamines Proteins 0.000 claims description 3
- 102000007327 Protamines Human genes 0.000 claims description 3
- 239000000412 dendrimer Substances 0.000 claims description 3
- 229920000736 dendritic polymer Polymers 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229940046166 oligodeoxynucleotide Drugs 0.000 claims description 3
- 230000002085 persistent effect Effects 0.000 claims description 3
- 229940048914 protamine Drugs 0.000 claims description 3
- 239000002047 solid lipid nanoparticle Substances 0.000 claims description 3
- 230000035882 stress Effects 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 241000700584 Simplexvirus Species 0.000 claims description 2
- 206010011005 corneal dystrophy Diseases 0.000 claims description 2
- 230000011664 signaling Effects 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 132
- 108091006267 SLC4A11 Proteins 0.000 claims 9
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 claims 4
- 108020004638 Circular DNA Proteins 0.000 claims 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 claims 1
- 230000002411 adverse Effects 0.000 claims 1
- 239000002479 lipoplex Substances 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 230000008470 skin growth Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 32
- 210000004027 cell Anatomy 0.000 description 319
- 150000001413 amino acids Chemical group 0.000 description 193
- 238000002045 capillary electrochromatography Methods 0.000 description 77
- 208000015636 celiac disease-epilepsy-cerebral calcification syndrome Diseases 0.000 description 77
- 235000018102 proteins Nutrition 0.000 description 50
- 210000001082 somatic cell Anatomy 0.000 description 49
- 210000004087 cornea Anatomy 0.000 description 34
- 239000003550 marker Substances 0.000 description 27
- 230000006870 function Effects 0.000 description 26
- 241000282414 Homo sapiens Species 0.000 description 23
- 239000002609 medium Substances 0.000 description 22
- 230000004069 differentiation Effects 0.000 description 21
- 230000008672 reprogramming Effects 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 108010028119 SLC4A Proteins Proteins 0.000 description 18
- 230000003389 potentiating effect Effects 0.000 description 18
- 210000001519 tissue Anatomy 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 210000000871 endothelium corneal Anatomy 0.000 description 17
- 108090000765 processed proteins & peptides Proteins 0.000 description 17
- 208000035475 disorder Diseases 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 230000007423 decrease Effects 0.000 description 13
- 210000001161 mammalian embryo Anatomy 0.000 description 13
- 210000001778 pluripotent stem cell Anatomy 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 12
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 11
- 230000027455 binding Effects 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 10
- 230000004568 DNA-binding Effects 0.000 description 9
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 9
- 230000002068 genetic effect Effects 0.000 description 9
- 230000014616 translation Effects 0.000 description 9
- 210000001109 blastomere Anatomy 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 238000010361 transduction Methods 0.000 description 8
- 230000026683 transduction Effects 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 108091023037 Aptamer Proteins 0.000 description 7
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 7
- 108010087132 Sodium-Bicarbonate Symporters Proteins 0.000 description 7
- 102000006633 Sodium-Bicarbonate Symporters Human genes 0.000 description 7
- 102100024270 Transcription factor SOX-2 Human genes 0.000 description 7
- 210000002555 descemet membrane Anatomy 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 210000002950 fibroblast Anatomy 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000008093 supporting effect Effects 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- 230000035897 transcription Effects 0.000 description 7
- 108091006112 ATPases Proteins 0.000 description 6
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 6
- 108010035532 Collagen Proteins 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 6
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 6
- 241000714474 Rous sarcoma virus Species 0.000 description 6
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 6
- 229920001436 collagen Polymers 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 210000002257 embryonic structure Anatomy 0.000 description 6
- 239000003623 enhancer Substances 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 230000006801 homologous recombination Effects 0.000 description 6
- 238000002744 homologous recombination Methods 0.000 description 6
- 230000000977 initiatory effect Effects 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 230000035800 maturation Effects 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 241000701022 Cytomegalovirus Species 0.000 description 5
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 5
- NLKVNZUFDPWPNL-YUMQZZPRSA-N Glu-Arg-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O NLKVNZUFDPWPNL-YUMQZZPRSA-N 0.000 description 5
- 108010026585 LIM homeobox transcription factor 1 beta Proteins 0.000 description 5
- 108700026244 Open Reading Frames Proteins 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 210000002459 blastocyst Anatomy 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 102000034356 gene-regulatory proteins Human genes 0.000 description 5
- 108091006104 gene-regulatory proteins Proteins 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 102000004888 Aquaporin 1 Human genes 0.000 description 4
- 108090001004 Aquaporin 1 Proteins 0.000 description 4
- 102100027314 Beta-2-microglobulin Human genes 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 4
- 101001139134 Homo sapiens Krueppel-like factor 4 Proteins 0.000 description 4
- 101000984042 Homo sapiens Protein lin-28 homolog A Proteins 0.000 description 4
- 102100020677 Krueppel-like factor 4 Human genes 0.000 description 4
- 108010085895 Laminin Proteins 0.000 description 4
- 102000007547 Laminin Human genes 0.000 description 4
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 4
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 102100025460 Protein lin-28 homolog A Human genes 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000004700 cellular uptake Effects 0.000 description 4
- 208000021921 corneal disease Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 210000001654 germ layer Anatomy 0.000 description 4
- 239000005090 green fluorescent protein Substances 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 210000002510 keratinocyte Anatomy 0.000 description 4
- 239000002679 microRNA Substances 0.000 description 4
- 210000003463 organelle Anatomy 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 230000003362 replicative effect Effects 0.000 description 4
- 239000002356 single layer Substances 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 230000005945 translocation Effects 0.000 description 4
- 241001529453 unidentified herpesvirus Species 0.000 description 4
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 3
- 102100038910 Alpha-enolase Human genes 0.000 description 3
- 201000004569 Blindness Diseases 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 102000000905 Cadherin Human genes 0.000 description 3
- 108050007957 Cadherin Proteins 0.000 description 3
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
- 102100034343 Integrase Human genes 0.000 description 3
- 108010061833 Integrases Proteins 0.000 description 3
- 102000003792 Metallothionein Human genes 0.000 description 3
- 108090000157 Metallothionein Proteins 0.000 description 3
- 241000713869 Moloney murine leukemia virus Species 0.000 description 3
- 102100025276 Monocarboxylate transporter 4 Human genes 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 102100028251 Phosphoglycerate kinase 1 Human genes 0.000 description 3
- 101710139464 Phosphoglycerate kinase 1 Proteins 0.000 description 3
- 108010019674 Proto-Oncogene Proteins c-sis Proteins 0.000 description 3
- 108091027981 Response element Proteins 0.000 description 3
- 108091006601 SLC16A3 Proteins 0.000 description 3
- 108091027967 Small hairpin RNA Proteins 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 208000020731 anterior segment dysgenesis 3 Diseases 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 230000004720 fertilization Effects 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000010362 genome editing Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 102000008371 intracellularly ATP-gated chloride channel activity proteins Human genes 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 230000008186 parthenogenesis Effects 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 102220278926 rs759871071 Human genes 0.000 description 3
- 239000004055 small Interfering RNA Substances 0.000 description 3
- 238000003892 spreading Methods 0.000 description 3
- 230000007480 spreading Effects 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- DDLZLOKCJHBUHD-WAVHTBQISA-N 6-bromoindirubin-3'-oxime Chemical compound O=C/1NC2=CC(Br)=CC=C2C\1=C\1/C(=N/O)/C2=CC=CC=C2N/1 DDLZLOKCJHBUHD-WAVHTBQISA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 102100032157 Adenylate cyclase type 10 Human genes 0.000 description 2
- 101710165425 Alpha-enolase Proteins 0.000 description 2
- 101710085823 Angiopoietin-related protein 7 Proteins 0.000 description 2
- 102100034598 Angiopoietin-related protein 7 Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 2
- 102100024210 CD166 antigen Human genes 0.000 description 2
- 238000010453 CRISPR/Cas method Methods 0.000 description 2
- 102000013392 Carboxylesterase Human genes 0.000 description 2
- 108010051152 Carboxylesterase Proteins 0.000 description 2
- 102000005367 Carboxypeptidases Human genes 0.000 description 2
- 108010006303 Carboxypeptidases Proteins 0.000 description 2
- 241000283153 Cetacea Species 0.000 description 2
- 101710128223 Chloride channel protein Proteins 0.000 description 2
- 102100023509 Chloride channel protein 2 Human genes 0.000 description 2
- 108010077544 Chromatin Proteins 0.000 description 2
- 108010069526 Collagen Type VIII Proteins 0.000 description 2
- 102000001191 Collagen Type VIII Human genes 0.000 description 2
- 208000028006 Corneal injury Diseases 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
- 102100020986 DNA-binding protein RFX5 Human genes 0.000 description 2
- 102100021044 DNA-binding protein RFXANK Human genes 0.000 description 2
- 101710205322 DNA-binding protein RFXANK Proteins 0.000 description 2
- 102100030091 Dickkopf-related protein 2 Human genes 0.000 description 2
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- 101710184673 Enolase 1 Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 241000282324 Felis Species 0.000 description 2
- 102100028412 Fibroblast growth factor 10 Human genes 0.000 description 2
- 108090001047 Fibroblast growth factor 10 Proteins 0.000 description 2
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 2
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 2
- 102000016970 Follistatin Human genes 0.000 description 2
- 108010014612 Follistatin Proteins 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 108060003393 Granulin Proteins 0.000 description 2
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 2
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 description 2
- 102100028970 HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 description 2
- 102100028966 HLA class I histocompatibility antigen, alpha chain F Human genes 0.000 description 2
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 2
- 108010075704 HLA-A Antigens Proteins 0.000 description 2
- 108010058607 HLA-B Antigens Proteins 0.000 description 2
- 108010050568 HLA-DM antigens Proteins 0.000 description 2
- 108010024164 HLA-G Antigens Proteins 0.000 description 2
- 102000009331 Homeodomain Proteins Human genes 0.000 description 2
- 108010048671 Homeodomain Proteins Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000775498 Homo sapiens Adenylate cyclase type 10 Proteins 0.000 description 2
- 101000980840 Homo sapiens CD166 antigen Proteins 0.000 description 2
- 101000906633 Homo sapiens Chloride channel protein 2 Proteins 0.000 description 2
- 101001075432 Homo sapiens DNA-binding protein RFX5 Proteins 0.000 description 2
- 101000864647 Homo sapiens Dickkopf-related protein 2 Proteins 0.000 description 2
- 101000986085 Homo sapiens HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 description 2
- 101000986080 Homo sapiens HLA class I histocompatibility antigen, alpha chain F Proteins 0.000 description 2
- 101000976713 Homo sapiens Integrin beta-like protein 1 Proteins 0.000 description 2
- 101000590830 Homo sapiens Monocarboxylate transporter 1 Proteins 0.000 description 2
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 2
- 101001094700 Homo sapiens POU domain, class 5, transcription factor 1 Proteins 0.000 description 2
- 101001019885 Homo sapiens Protein MGARP Proteins 0.000 description 2
- 101000713275 Homo sapiens Solute carrier family 22 member 3 Proteins 0.000 description 2
- 101000732345 Homo sapiens Transcription factor AP-2-beta Proteins 0.000 description 2
- 101000850658 Homo sapiens Voltage-dependent anion-selective channel protein 3 Proteins 0.000 description 2
- 101000744897 Homo sapiens Zinc finger homeobox protein 4 Proteins 0.000 description 2
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102100023481 Integrin beta-like protein 1 Human genes 0.000 description 2
- 239000000232 Lipid Bilayer Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 108700002010 MHC class II transactivator Proteins 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102100034068 Monocarboxylate transporter 1 Human genes 0.000 description 2
- 102100025272 Monocarboxylate transporter 2 Human genes 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108050000637 N-cadherin Proteins 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- 101150031628 PITX2 gene Proteins 0.000 description 2
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 description 2
- 229920001100 Polydextrose Polymers 0.000 description 2
- 101710101148 Probable 6-oxopurine nucleoside phosphorylase Proteins 0.000 description 2
- 102000048176 Prostaglandin-D synthases Human genes 0.000 description 2
- 108030003866 Prostaglandin-D synthases Proteins 0.000 description 2
- 102100035797 Protein MGARP Human genes 0.000 description 2
- 101710149951 Protein Tat Proteins 0.000 description 2
- 102000030764 Purine-nucleoside phosphorylase Human genes 0.000 description 2
- 101710132082 Pyrimidine/purine nucleoside phosphorylase Proteins 0.000 description 2
- 102100021043 Regulatory factor X-associated protein Human genes 0.000 description 2
- 101710189356 Regulatory factor X-associated protein Proteins 0.000 description 2
- 108091006604 SLC16A7 Proteins 0.000 description 2
- 108091006647 SLC9A1 Proteins 0.000 description 2
- 241000701062 Saimiriine gammaherpesvirus 2 Species 0.000 description 2
- 102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 description 2
- 238000010459 TALEN Methods 0.000 description 2
- 206010043276 Teratoma Diseases 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102100031372 Thymidine phosphorylase Human genes 0.000 description 2
- 102100034686 Tight junction protein ZO-1 Human genes 0.000 description 2
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 2
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 2
- 102100033348 Transcription factor AP-2-beta Human genes 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 108010022109 Voltage-Dependent Anion Channel 2 Proteins 0.000 description 2
- 102100033099 Voltage-dependent anion-selective channel protein 3 Human genes 0.000 description 2
- 102100039968 Zinc finger homeobox protein 4 Human genes 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000004115 adherent culture Methods 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000002159 anterior chamber Anatomy 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000001612 chondrocyte Anatomy 0.000 description 2
- 210000003483 chromatin Anatomy 0.000 description 2
- 238000007398 colorimetric assay Methods 0.000 description 2
- 210000003683 corneal stroma Anatomy 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 108010085933 diguanylate cyclase Proteins 0.000 description 2
- 108020001096 dihydrofolate reductase Proteins 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 210000003981 ectoderm Anatomy 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 210000001900 endoderm Anatomy 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000003560 epithelium corneal Anatomy 0.000 description 2
- 231100000040 eye damage Toxicity 0.000 description 2
- 230000004438 eyesight Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 229940098448 fibroblast growth factor 7 Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 108010085237 homeobox protein PITX2 Proteins 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000009191 jumping Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 210000002752 melanocyte Anatomy 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- 210000003716 mesoderm Anatomy 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 239000001259 polydextrose Substances 0.000 description 2
- 229940035035 polydextrose Drugs 0.000 description 2
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 208000037920 primary disease Diseases 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000011506 response to oxidative stress Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 238000010374 somatic cell nuclear transfer Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 238000004114 suspension culture Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 229960000278 theophylline Drugs 0.000 description 2
- 210000000515 tooth Anatomy 0.000 description 2
- 230000005026 transcription initiation Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- LKUDPHPHKOZXCD-UHFFFAOYSA-N 1,3,5-trimethoxybenzene Chemical compound COC1=CC(OC)=CC(OC)=C1 LKUDPHPHKOZXCD-UHFFFAOYSA-N 0.000 description 1
- SGKGZYGMLGVQHP-ZOQUXTDFSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-methylpyrimidine-2,4-dione Chemical compound CC1=CC(=O)NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 SGKGZYGMLGVQHP-ZOQUXTDFSA-N 0.000 description 1
- 101800001622 120 kDa surface-exposed protein Proteins 0.000 description 1
- SHCCKWGIFIPGNJ-NSUCVBPYSA-N 2-aminoethyl [(2r)-2,3-bis[(z)-octadec-9-enoxy]propyl] hydrogen phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCCOC[C@H](COP(O)(=O)OCCN)OCCCCCCCC\C=C/CCCCCCCC SHCCKWGIFIPGNJ-NSUCVBPYSA-N 0.000 description 1
- JLIDBLDQVAYHNE-LXGGSRJLSA-N 2-cis-abscisic acid Chemical compound OC(=O)/C=C(/C)\C=C\C1(O)C(C)=CC(=O)CC1(C)C JLIDBLDQVAYHNE-LXGGSRJLSA-N 0.000 description 1
- VPLZGVOSFFCKFC-UHFFFAOYSA-N 3-methyluracil Chemical compound CN1C(=O)C=CNC1=O VPLZGVOSFFCKFC-UHFFFAOYSA-N 0.000 description 1
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 1
- ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- AGFIRQJZCNVMCW-UAKXSSHOSA-N 5-bromouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 AGFIRQJZCNVMCW-UAKXSSHOSA-N 0.000 description 1
- ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 description 1
- 239000013607 AAV vector Substances 0.000 description 1
- 241001455214 Acinonyx jubatus Species 0.000 description 1
- 108010059616 Activins Proteins 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 1
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 1
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 1
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 1
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 1
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 1
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 1
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 1
- 241000649045 Adeno-associated virus 10 Species 0.000 description 1
- 241000958487 Adeno-associated virus 3B Species 0.000 description 1
- 241000589158 Agrobacterium Species 0.000 description 1
- 241000282452 Ailuropoda melanoleuca Species 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 101710101449 Alpha-centractin Proteins 0.000 description 1
- 102100030346 Antigen peptide transporter 1 Human genes 0.000 description 1
- 102100030343 Antigen peptide transporter 2 Human genes 0.000 description 1
- 101150019028 Antp gene Proteins 0.000 description 1
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 201000009193 Axenfeld-Rieger syndrome type 1 Diseases 0.000 description 1
- 201000009189 Axenfeld-Rieger syndrome type 3 Diseases 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102000015735 Beta-catenin Human genes 0.000 description 1
- 108060000903 Beta-catenin Proteins 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 1
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 1
- 241000701922 Bovine parvovirus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 108091033409 CRISPR Proteins 0.000 description 1
- 238000010354 CRISPR gene editing Methods 0.000 description 1
- 102100036364 Cadherin-2 Human genes 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 108090000567 Caspase 7 Proteins 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 102100038902 Caspase-7 Human genes 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 102100033780 Collagen alpha-3(IV) chain Human genes 0.000 description 1
- 102000001045 Connexin 43 Human genes 0.000 description 1
- 108010069241 Connexin 43 Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102100040501 Contactin-associated protein 1 Human genes 0.000 description 1
- 208000006069 Corneal Opacity Diseases 0.000 description 1
- 241001125840 Coryphaenidae Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000000311 Cytosine Deaminase Human genes 0.000 description 1
- 108010080611 Cytosine Deaminase Proteins 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 101000836720 Dictyostelium discoideum Aldose reductase A Proteins 0.000 description 1
- 108700006830 Drosophila Antp Proteins 0.000 description 1
- 101000595915 Drosophila melanogaster Procollagen-lysine,2-oxoglutarate 5-dioxygenase Proteins 0.000 description 1
- 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010031111 EBV-encoded nuclear antigen 1 Proteins 0.000 description 1
- 108700035208 EC 7.-.-.- Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 102100038083 Endosialin Human genes 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 101710088283 Forkhead box protein C1 Proteins 0.000 description 1
- 102000001267 GSK3 Human genes 0.000 description 1
- 108060006662 GSK3 Proteins 0.000 description 1
- 241000701047 Gallid alphaherpesvirus 2 Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 1
- 102100033079 HLA class II histocompatibility antigen, DM alpha chain Human genes 0.000 description 1
- 102100031258 HLA class II histocompatibility antigen, DM beta chain Human genes 0.000 description 1
- 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 description 1
- 102100031546 HLA class II histocompatibility antigen, DO beta chain Human genes 0.000 description 1
- 102100036243 HLA class II histocompatibility antigen, DQ alpha 1 chain Human genes 0.000 description 1
- 102100036241 HLA class II histocompatibility antigen, DQ beta 1 chain Human genes 0.000 description 1
- 102100040505 HLA class II histocompatibility antigen, DR alpha chain Human genes 0.000 description 1
- 108010052199 HLA-C Antigens Proteins 0.000 description 1
- 108010041384 HLA-DPA antigen Proteins 0.000 description 1
- 108010086786 HLA-DQA1 antigen Proteins 0.000 description 1
- 108010067148 HLA-DQbeta antigen Proteins 0.000 description 1
- 108010067802 HLA-DR alpha-Chains Proteins 0.000 description 1
- 241000713858 Harvey murine sarcoma virus Species 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 108010061414 Hepatocyte Nuclear Factor 1-beta Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000986621 Homo sapiens ATP-binding cassette sub-family C member 6 Proteins 0.000 description 1
- 101000882335 Homo sapiens Alpha-enolase Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 description 1
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 1
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 description 1
- 101100382122 Homo sapiens CIITA gene Proteins 0.000 description 1
- 101000714537 Homo sapiens Cadherin-2 Proteins 0.000 description 1
- 101000710873 Homo sapiens Collagen alpha-3(IV) chain Proteins 0.000 description 1
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 1
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
- 101000884275 Homo sapiens Endosialin Proteins 0.000 description 1
- 101100013370 Homo sapiens FOXC1 gene Proteins 0.000 description 1
- 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 description 1
- 101000866281 Homo sapiens HLA class II histocompatibility antigen, DO beta chain Proteins 0.000 description 1
- 101001046564 Homo sapiens Krueppel-like factor 13 Proteins 0.000 description 1
- 101100464684 Homo sapiens POU6F2 gene Proteins 0.000 description 1
- 101000613490 Homo sapiens Paired box protein Pax-3 Proteins 0.000 description 1
- 101000601661 Homo sapiens Paired box protein Pax-7 Proteins 0.000 description 1
- 101001115830 Homo sapiens Prostate-associated microseminoprotein Proteins 0.000 description 1
- 101001072191 Homo sapiens Protein disulfide-isomerase A2 Proteins 0.000 description 1
- 101000904783 Homo sapiens Putative tyrosine-protein phosphatase auxilin Proteins 0.000 description 1
- 101000825432 Homo sapiens SHC-transforming protein 4 Proteins 0.000 description 1
- 101001092910 Homo sapiens Serum amyloid P-component Proteins 0.000 description 1
- 101000701334 Homo sapiens Sodium/potassium-transporting ATPase subunit alpha-1 Proteins 0.000 description 1
- 101000802356 Homo sapiens Tight junction protein ZO-1 Proteins 0.000 description 1
- 101000806424 Homo sapiens V-type proton ATPase subunit G 1 Proteins 0.000 description 1
- 101000976622 Homo sapiens Zinc finger protein 42 homolog Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 102100026818 Inhibin beta E chain Human genes 0.000 description 1
- 108020005350 Initiator Codon Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 102100022254 Krueppel-like factor 13 Human genes 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 101150096639 LMX1B gene Proteins 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102100025069 MARVEL domain-containing protein 1 Human genes 0.000 description 1
- 108700005089 MHC Class I Genes Proteins 0.000 description 1
- 102100026371 MHC class II transactivator Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010023335 Member 2 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 108010057081 Merozoite Surface Protein 1 Proteins 0.000 description 1
- 101100128482 Mesocricetus auratus LMX1B gene Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- 108091028232 Mir-184 Proteins 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000000175 Nail-Patella Syndrome Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108090000304 Occludin Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 240000007019 Oxalis corniculata Species 0.000 description 1
- 208000025174 PANDAS Diseases 0.000 description 1
- 102000007354 PAX6 Transcription Factor Human genes 0.000 description 1
- 101150081664 PAX6 gene Proteins 0.000 description 1
- 208000021155 Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Diseases 0.000 description 1
- 102100040891 Paired box protein Pax-3 Human genes 0.000 description 1
- 102100037503 Paired box protein Pax-7 Human genes 0.000 description 1
- 240000004718 Panda Species 0.000 description 1
- 235000016496 Panda oleosa Nutrition 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 1
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 101710106040 Pituitary homeobox 2 Proteins 0.000 description 1
- 108010071690 Prealbumin Proteins 0.000 description 1
- 102000007584 Prealbumin Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100022407 Probable 28S rRNA (cytosine(4447)-C(5))-methyltransferase Human genes 0.000 description 1
- 241000283080 Proboscidea <mammal> Species 0.000 description 1
- 241000282335 Procyon Species 0.000 description 1
- 102100025013 Prostate-associated microseminoprotein Human genes 0.000 description 1
- 102100036351 Protein disulfide-isomerase A2 Human genes 0.000 description 1
- 108010018070 Proto-Oncogene Proteins c-ets Proteins 0.000 description 1
- 102000004053 Proto-Oncogene Proteins c-ets Human genes 0.000 description 1
- 102100023922 Putative tyrosine-protein phosphatase auxilin Human genes 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- 102100022333 SHC-transforming protein 4 Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108700025832 Serum Response Element Proteins 0.000 description 1
- 102100036202 Serum amyloid P-component Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102100030458 Sodium/potassium-transporting ATPase subunit alpha-1 Human genes 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 241000713880 Spleen focus-forming virus Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 101150116168 TFAP2B gene Proteins 0.000 description 1
- 101800000849 Tachykinin-associated peptide 2 Proteins 0.000 description 1
- 101710192266 Tegument protein VP22 Proteins 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108050005627 Transcription factor AP-2 beta Proteins 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 102100037433 V-type proton ATPase subunit G 1 Human genes 0.000 description 1
- 102000008790 VE-cadherin Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010047531 Visual acuity reduced Diseases 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 102000013814 Wnt Human genes 0.000 description 1
- 108050003627 Wnt Proteins 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 102100023550 Zinc finger protein 42 homolog Human genes 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000488 activin Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 210000004504 adult stem cell Anatomy 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000030787 anterior segment dysgenesis 4 Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000004009 axon guidance Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 208000013404 behavioral symptom Diseases 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000003012 bilayer membrane Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000004703 blastocyst inner cell mass Anatomy 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- PKFDLKSEZWEFGL-MHARETSRSA-N c-di-GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]3[C@@H](O)[C@H](N4C5=C(C(NC(N)=N5)=O)N=C4)O[C@@H]3COP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 PKFDLKSEZWEFGL-MHARETSRSA-N 0.000 description 1
- 108010018828 cadherin 5 Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 210000001011 carotid body Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000003763 chloroplast Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 108010008846 chordin Proteins 0.000 description 1
- 102000006533 chordin Human genes 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000004453 corneal transparency Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- ZPTBLXKRQACLCR-XVFCMESISA-N dihydrouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)CC1 ZPTBLXKRQACLCR-XVFCMESISA-N 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- XHBVYDAKJHETMP-UHFFFAOYSA-N dorsomorphin Chemical compound C=1C=C(C2=CN3N=CC(=C3N=C2)C=2C=CN=CC=2)C=CC=1OCCN1CCCCC1 XHBVYDAKJHETMP-UHFFFAOYSA-N 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 1
- 210000001705 ectoderm cell Anatomy 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000004039 endoderm cell Anatomy 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000002514 epidermal stem cell Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004373 eye development Effects 0.000 description 1
- VLMZMRDOMOGGFA-WDBKCZKBSA-N festuclavine Chemical compound C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C)=C3C2=CNC3=C1 VLMZMRDOMOGGFA-WDBKCZKBSA-N 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 210000000604 fetal stem cell Anatomy 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 230000003328 fibroblastic effect Effects 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 239000003540 gamma secretase inhibitor Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 230000010005 growth-factor like effect Effects 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 210000000442 hair follicle cell Anatomy 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 210000003897 hepatic stem cell Anatomy 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 102000055647 human CSF2RB Human genes 0.000 description 1
- 102000049879 human FOXC1 Human genes 0.000 description 1
- 102000051564 human POU6F2 Human genes 0.000 description 1
- 102000057652 human TFAP2B Human genes 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000010365 information processing Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000013275 interstitial granulomatous dermatitis with arthritis Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000037041 intracellular level Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 201000008633 iridogoniodysgenesis syndrome Diseases 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011901 isothermal amplification Methods 0.000 description 1
- ZNJFBWYDHIGLCU-HWKXXFMVSA-N jasmonic acid Chemical compound CC\C=C/C[C@@H]1[C@@H](CC(O)=O)CCC1=O ZNJFBWYDHIGLCU-HWKXXFMVSA-N 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 108010038862 laminin 10 Proteins 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 210000001704 mesoblast Anatomy 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 210000004944 mitochondria-rich cell Anatomy 0.000 description 1
- 230000025608 mitochondrion localization Effects 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 210000000472 morula Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 210000001982 neural crest cell Anatomy 0.000 description 1
- 210000005155 neural progenitor cell Anatomy 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 210000000276 neural tube Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 102000045246 noggin Human genes 0.000 description 1
- 108700007229 noggin Proteins 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 230000008723 osmotic stress Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 208000030825 patent ductus arteriosus 2 Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical compound NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229930195732 phytohormone Natural products 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 230000003234 polygenic effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 102000005912 ran GTP Binding Protein Human genes 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000030198 regulation of embryonic development Effects 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 210000003497 sciatic nerve Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 208000037921 secondary disease Diseases 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 229910010271 silicon carbide Inorganic materials 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000002356 skeleton Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000037423 splicing regulation Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 108010012374 type IV collagen alpha3 chain Proteins 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0618—Cells of the nervous system
- C12N5/0621—Eye cells, e.g. cornea, iris pigmented cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/38—Vitamins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/70—Undefined extracts
- C12N2500/80—Undefined extracts from animals
- C12N2500/84—Undefined extracts from animals from mammals
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/113—Acidic fibroblast growth factor (aFGF, FGF-1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/115—Basic fibroblast growth factor (bFGF, FGF-2)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/155—Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/70—Enzymes
- C12N2501/72—Transferases (EC 2.)
- C12N2501/727—Kinases (EC 2.7.)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/45—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from artificially induced pluripotent stem cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/50—Proteins
- C12N2533/52—Fibronectin; Laminin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
- C12N2830/002—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biophysics (AREA)
- Developmental Biology & Embryology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本發明提供藉由增加角膜內皮祖細胞中之轉錄因子之表現來產生角膜內皮細胞(例如,成熟角膜內皮細胞)之方法,及其組合物。
Description
本發明係關於用於產生成熟角膜內皮細胞及其組合物之方法。
角膜發揮對於正常視力及維持眼睛健康而言重要的功能,包括提供眼睛之約三分之二的屈光力及保護眼睛免受損傷或感染。在世界範圍內,角膜疾病及損傷為失明之主要原因。許多角膜疾病及損傷可藉由移植供體角膜來治療。在過去的15年中,角膜為身體內移植最多的器官且具有高成功率。舉例而言,在美國每年進行約40,000例角膜移植。然而,在世界範圍內,對用於移植的角膜之需求遠超過當前供應源,且可用的供體組織之有限的品質及數量阻礙了治療。一種造成供給角膜之供應源不足的因素為多達30%的供給角膜由於角膜內皮之品質不良而被拒絕用於移植。角膜內皮之品質通常隨供體年齡而降低,因為隨著角膜老化或受損,內皮細胞死亡且未被替換。因此,隨著人群老齡化,具有適合的健康角膜內皮之供體組織之供應源減少。此外,預期供給角膜之數目及品質會隨著LASIK手術之風行度增加而降低(此等角膜被拒絕用於移植)。
角膜疾病可涉及角膜之五個層中之一或多者:角膜上皮、鮑曼層(Bowman's layer)、角膜基質、後彈力膜(Descemet's membrane)及角膜內皮。角膜上皮、角膜基質及角膜內皮為細胞層,而鮑曼層及後彈力膜主要由膠原蛋白纖維構成。角膜內皮為角膜之內表面上的細胞單層。其面向角膜與虹膜之間形成的腔室且藉由調節流體水準來保持角膜透明。若不存在功能性角膜內皮,則角膜變得混濁且視力受損。正常發揮功能之角膜內皮細胞維持角膜中之適當流體水準,例如,流體「滲漏」至基質中與主動泵送之間的平衡,該主動泵送連續操作以使流體自基質移動至眼睛之前房。
已報導角膜內皮細胞幾乎不具有或不具有活體內增殖之能力,使得其在受損或以其他方式損失時不能被替換。在人類中,角膜內皮細胞層在出生時之填充密集度最高且隨後細胞密度隨著眼睛生長而快速降低(反映為相同數目之細胞覆蓋更大的區域)。隨後,角膜細胞密度隨著年齡的增長而逐漸降低,明顯地反映不能被替換的細胞之逐漸損失。隨著細胞密度降低,各細胞展開且覆蓋更大的區域以維持細胞層之障壁及泵送功能。然而,若細胞密度降低過多(低於約500至1000個細胞/mm
2),則其功能受損,引起角膜混濁、基質水腫、視力損失且最終失明。特定言之,已報告在年齡為兩個月之嬰兒中,活體內緊密填充之角膜內皮之細胞密度高達5624個細胞/mm
2,在出生後第一年內降低至4252個細胞/mm
2,且接著在早期兒童期快速降低(與角膜尺寸隨著眼睛生長而增加相關)。在5歲時,角膜內皮密度降低至約3591±399個細胞/mm
2且在10歲時進一步降低至約2697±246個細胞/mm
2,且在整個成人期每年進一步降低約0.6%。參見Peh等人, Transplantation. 2011年4月, 27; 91(8):811-9。
影響角膜內皮之原發性疾病包括法曲氏營養不良(Fuch's dystrophy)、虹膜角膜內皮症候群、後部多形性營養不良及先天性遺傳性內皮營養不良。最有效之治療為更換角膜內皮之繼發性疾病包括若干種角膜營養不良、隱形眼鏡之使用、白內障手術及角膜移植中之晚期內皮衰竭。當僅角膜內皮受損時,較佳治療為後彈力膜剝除伴內皮角膜成形術(Descemet's stripping with endothelial keratoplasty;DSEK),其包括移除後彈力膜及角膜內皮且隨後移植供體組織。或者,在穿透性角膜移植(PKP)中,移除且更換整個角膜。
通常,角膜移植包括獲得供體角膜(例如,來自死後解剖捐贈物)、測定供體角膜是否具有足夠的品質且在其他方面適用,及手術更換受損或患病的角膜。已研發出用於更換整個角膜(穿透性角膜移植)或保留患者之後彈力膜及內皮且用供給組織更換其餘層(板層角膜移植)之程序;後一種程序可降低移植排斥之風險,但亦可能引起移植後之視力較差。此外,板層角膜移植可能不適用於治療一些其中更換患者之角膜內皮及/或後彈力膜可能為指定治療之病狀。通常參見美國專利案第5,755,785號、美國專利案第5,649,944號、美國專利案第7,147,648號、美國專利案第7,300,653號、美國專利案第5,584,881號、美國專利案第5,686,414號、美國專利案第7,300,654號、美國專利申請案第10/525,391號,其各自以全文引用的方式併入本文中。正在研發角膜內皮手術更換之其他方法,包括後彈力膜內皮角膜成形術(Descemet's Membrane Endothelial Keratoplasty;DMEK),其中供體組織僅由後彈力膜及角膜內皮組成。另一種可能有前景的治療途徑為角膜內皮重構,其中在移植之前在活體外培養角膜內皮細胞。舉例而言,在聚合物上培養所供給之人類角膜細胞,釋放至生物黏著性明膠盤上,且接著成功地整合至經剝離之兔角膜中,其中明膠盤在移植之後溶解(Hsiue等人, Transplantation. 2006年2月, 15; 81(3):473-6,其以全文引用之方式併入本文中)。然而,利用培養物細胞之方法需要具有該等細胞之來源,且因此受如上文所描述之缺乏適合的供給組織之影響。此外,由於供給細胞之差異,發現難以產生具有恆定的品質及功效之角膜內皮細胞培養物。由於可能需要對自各供體獲得之細胞進行廣泛的安全性及/或功效測試,因此監管障礙亦可能使此類方法在後勤方面難以大規模進行。此等及其他治療方法進一步描述於Thomas John, Corneal Endothelial Transplant: DSAEK, DMEK & DLEK (JP Medical Ltd, 2010)中,其以全文引用之方式併入本文中。
其他大體上關於獲得及使用角膜細胞之方法(包括治療方法、培養方法、保存方法)、含有角膜細胞或可與角膜細胞結合使用之組合物及其類似物之揭示內容包括於U.S. 2007/0275365、US 2010/0209402、US 2010/0233240、US 2011/0009488、US 2009/0232772、美國專利案第5,166,048號、US 2007/0092550、US 2005/0214259、US 2007/0148137、美國專利案第4,959,319號、美國專利案第5,310,728號、美國專利案第5,589,451號、US 2010/0215717、美國專利案第5,703,047號、US 2009/0222086、US 2009/0263465、US 2006/0228693、US 2006/0240552、US 2009/0270982、美國專利案第5,269,812號、美國專利案第7,371,513號、US 2010/0069915、US 2011/0166650、U.S. 9,752,118、US 2018/0072989及U.S. 9,752,118中,其各自以全文引用之方式併入本文中。
因此,此項技術中需要用於製備角膜內皮細胞之簡單及有效的方法。
本發明藉由提供可行且有效的用於製備角膜內皮細胞(CEC),例如成熟CEC之方法來滿足此項技術中之此需求,該等方法係藉由增加角膜內皮祖細胞或富潛能幹細胞(例如,誘導性富潛能幹細胞或胚胎幹細胞)中之至少一種選自由以下組成之群之轉錄因子之表現來進行:成對樣同源域轉錄因子2 (PITX2)、叉頭框C1 (FOXC1)、轉錄因子AP-2β (TFAP2B)、LIM同源匣轉錄因子1β (LMX1B)及POU6F2 (第6類Pou同源盒2)。在一個態樣中,本發明提供新穎及有效的用於產生CEC,例如成熟CEC之方法,其係藉由增加角膜內皮祖細胞或富潛能幹細胞(例如,誘導性富潛能幹細胞或胚胎幹細胞)中之至少一種選自由以下組成之群之轉錄因子之表現來進行:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
本發明之方法皆為簡單、可行及有效的,且引起產生可用於本文中所揭示之各種應用(例如,治療眼部疾病,例如CEC之疾病)之CEC,例如成熟CEC。
本發明提供用於產生角膜內皮細胞之方法,該方法包含增加角膜內皮祖細胞中之至少一種選自由PITX2、FOXC1、TFAP2B、LMX1B及POU6F2組成之群之轉錄因子之表現,藉此產生角膜內皮細胞。
在某些實施例中,PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在某些實施例中,PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在一個實施例中,角膜內皮細胞為成熟角膜內皮細胞。
在另一實施例中,轉錄因子為PITX2。
在另一實施例中,PITX2為至少一種選自由以下組成之群之PITX2之同功型:PITX2,同功型1;PITX2,同功型2;PITX2,同功型3;PITX2,同功型4;及PITX2,同功型5。
在另一實施例中,轉錄因子為FOXC1。
在另一實施例中,轉錄因子為TFAP2B。
在另一實施例中,TFAP2B為至少一種選自由以下組成之群之TFAP2B之同功型:TFAP2B,同功型1及TFAP2B,同功型2。
在另一實施例中,轉錄因子為LMX1B。
在另一實施例中,LMX1B為至少一種選自由以下組成之群之LMX1B之同功型:LMX1B,同功型1;LMX1B,同功型2;及LMX1B,同功型3。
在另一實施例中,轉錄因子為POU6F2。
在另一實施例中,POU6F2為至少一種選自由以下組成之群之POU6F2之同功型:POU6F2,同功型1及POU6F2,同功型2。
在另一實施例中,方法進一步包含增加角膜內皮祖細胞中之一或多種選自由以下組成之群之轉錄因子之表現:ERG、ATF4、ATMIN、BHLHE40、CEBPD、CSRNP1、DRAP1、EGR1、ELF2、EMX2、ESRRA、ETS2、FOS、FOSB、FOSL2、GTF3A、HIF1A、JUN、JUNB、JUND、KLF10、KLF9、MBD3、NFE2L1、NME2、NR1D1、NR4A1、PA2G4、POU3F3、RELA、TBX2、TFDP1、TSC22D1、USF2、YBX1、ZNF207、ZNF358及ZNF395。
在另一實施例中,該一或多種轉錄因子為ERG。在另一實施例中,該一或多種轉錄因子為BHLHE40。在另一實施例中,該一或多種轉錄因子為CEBPD。在另一實施例中,該一或多種轉錄因子為CSRNP1。在另一實施例中,該一或多種轉錄因子為EGR1。在另一實施例中,該一或多種轉錄因子為ESRRA。在另一實施例中,該一或多種轉錄因子為ETS2。在另一實施例中,該一或多種轉錄因子為FOS。在另一實施例中,該一或多種轉錄因子為FOSB。在另一實施例中,該一或多種轉錄因子為FOSL2。在另一實施例中,該一或多種轉錄因子為JUN。在另一實施例中,該一或多種轉錄因子為JUNB。在另一實施例中,該一或多種轉錄因子為JUND。在另一實施例中,該一或多種轉錄因子為KLF10。在另一實施例中,該一或多種轉錄因子為KLF9。在另一實施例中,該一或多種轉錄因子為NR1D1。在另一實施例中,該一或多種轉錄因子為NR4A1。在另一實施例中,該一或多種轉錄因子為TSC22D1。
在另一實施例中,增加角膜內皮祖細胞中之至少一種轉錄因子之表現包含使角膜內皮祖細胞與至少一種轉錄因子接觸。
在另一實施例中,角膜內皮祖細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體。
在另一實施例中,角膜內皮祖細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體包含自我裂解序列。
在另一實施例中,角膜內皮祖細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體為病毒載體。
在另一實施例中,角膜內皮祖細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體為非病毒載體。
在另一實施例中,角膜內皮祖細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體為誘導型表現載體。
在另一實施例中,角膜內皮祖細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體包含以可操作方式連接至編碼至少一種轉錄因子之核酸之啟動子。
在一個實施例中,啟動子為內源性啟動子。
在一個實施例中,啟動子為人工啟動子。
在一個實施例中,啟動子為誘導型啟動子。
在另一實施例中,增加角膜內皮祖細胞中之至少一種轉錄因子之表現包含用編碼至少一種轉錄因子之病毒載體轉導角膜內皮祖細胞。
在另一實施例中,增加角膜內皮祖細胞中之至少一種轉錄因子之表現包含用編碼至少一種轉錄因子之表現載體轉染角膜內皮祖細胞。
在另一實施例中,在增加至少一種轉錄因子之表現之前,將角膜內皮祖細胞培養至少2、3、4、5、6、7、8、9、10、11或12天。
在另一實施例中,在增加至少一種轉錄因子之表現之後,將角膜內皮祖細胞培養至少10、12、14、16、18、20、21、22、23、24、25、26、27、28、29或30天。
在另一實施例中,增加PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。
在另一實施例中,增加FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,增加TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,增加LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,增加POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞呈現增加的一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B、LMX1B及MRGPRX3。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞呈現增加的一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B及LMX1B。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞呈現增加的一或多種選自由以下組成之群之標記物之表現:COL8A1、COL8A2、SLC4A11及MRGPRX3。
在另一實施例中,增加的一或多種標記物之表現包含相對於角膜內皮祖細胞增加至少2倍、5倍、10倍、50倍、100倍、200倍、500倍、1,000倍、2,000倍、5,000倍或10,000倍。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞呈現降低之NGFR、SOX10、HNK1、SSEA4、NANOG、OCT4、vWF及/或CD31之表現。
在另一實施例中,降低之NGFR、SOX10、HNK1、SSEA4、NANOG、OCT4、vWF及/或CD31之表現包含相對於角膜內皮祖細胞降低至少0.1倍、0.2倍、0.5倍、1倍、2倍、3倍或4倍。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞呈現以下中之一或多者:增加之泵送功能、增強之緊密接合區形成、增加之對氧化應力之抗性及增加之多邊形形態。
在另一實施例中,增加之泵送功能、增強之緊密接合區形成、增加之對氧化應力之抗性及增加之多邊形形態包含相對於角膜內皮祖細胞增加至少5%、10%、15%、20%或25%。
在另一實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本朝向角膜內皮細胞之總轉錄本偏移至少1%、5%、10%、20%、30%、40%或50%。
在另一實施例中,在向有需要之個體之角膜投與角膜內皮細胞後,角膜呈現以下中之一或多者:增加之泵送活性、增加之緊密接合區形成、增加之對氧化應力之抗性、增加之透明度及降低之厚度。
在另一實施例中,角膜內皮祖細胞係衍生自富潛能幹細胞。
在另一實施例中,角膜內皮祖細胞係衍生自富潛能幹細胞,該等富潛能幹細胞為胚胎幹細胞或誘導性富潛能幹細胞。
在另一實施例中,誘導角膜內皮祖細胞中之至少一種轉錄因子之表現包含使用編碼該至少一種轉錄因子之基因開關構築體。
在另一實施例中,誘導角膜內皮祖細胞中之至少一種轉錄因子之表現包含使用編碼該至少一種轉錄因子之基因開關構築體,其中該基因開關構築體為轉錄基因開關構築體。
在另一實施例中,誘導角膜內皮祖細胞中之至少一種轉錄因子之表現包含使用編碼該至少一種轉錄因子之基因開關構築體,其中該基因開關構築體為轉錄後基因開關構築體。
本發明亦提供用於產生富潛能幹細胞衍生之角膜內皮細胞之方法,該方法包含:(a)培養富潛能幹細胞及誘導角膜內皮祖細胞或神經脊幹細胞之形成,其中富潛能幹細胞包含有包含編碼至少一種選自由以下組成之群之轉錄因子之核酸之表現載體:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2,及(b)增加角膜內皮祖細胞或神經脊幹細胞中之該至少一種來自表現載體之轉錄因子之表現,藉此產生角膜內皮細胞。
在某些實施例中,PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在某些實施例中,PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在一個實施例中,角膜內皮細胞為成熟角膜內皮細胞。
在另一實施例中,富潛能幹細胞為胚胎幹細胞。
在另一實施例中,富潛能幹細胞為誘導性富潛能幹細胞。
在另一實施例中,轉錄因子為PITX2。
在另一實施例中,PITX2為至少一種選自由以下組成之群之PITX2之同功型:PITX2,同功型1;PITX2,同功型2;PITX2,同功型3;PITX2,同功型4;及PITX2,同功型5。
在另一實施例中,轉錄因子為FOXC1。
在另一實施例中,轉錄因子為TFAP2B。
在另一實施例中,TFAP2B為至少一種選自由以下組成之群之TFAP2B之同功型:TFAP2B,同功型1及TFAP2B,同功型2。
在另一實施例中,轉錄因子為LMX1B。
在另一實施例中,LMX1B為至少一種選自由以下組成之群之LMX1B之同功型:LMX1B,同功型1;LMX1B,同功型2;及LMX1B,同功型3。
在另一實施例中,轉錄因子為POU6F2。
在另一實施例中,POU6F2為至少一種選自由以下組成之群之POU6F2之同功型:POU6F2,同功型1及POU6F2,同功型2。
在另一實施例中,方法進一步包含增加一或多種選自由以下組成之群之轉錄因子之表現:ERG、ATF4、ATMIN、BHLHE40、CEBPD、CSRNP1、DRAP1、EGR1、ELF2、EMX2、ESRRA、ETS2、FOS、FOSB、FOSL2、GTF3A、HIF1A、JUN、JUNB、JUND、KLF10、KLF9、MBD3、NFE2L1、NME2、NR1D1、NR4A1、PA2G4、POU3F3、RELA、TBX2、TFDP1、TSC22D1、USF2、YBX1、ZNF207、ZNF358及ZNF395。
在另一實施例中,一或多種轉錄因子為ERG。在另一實施例中,一或多種轉錄因子為BHLHE40。在另一實施例中,一或多種轉錄因子為CEBPD。在另一實施例中,一或多種轉錄因子為CSRNP1。在另一實施例中,一或多種轉錄因子為EGR1。在另一實施例中,一或多種轉錄因子為ESRRA。在另一實施例中,一或多種轉錄因子為ETS2。在另一實施例中,一或多種轉錄因子為FOS。在另一實施例中,一或多種轉錄因子為FOSB。在另一實施例中,一或多種轉錄因子為FOSL2。在另一實施例中,一或多種轉錄因子為JUN。在另一實施例中,一或多種轉錄因子為JUNB。在另一實施例中,一或多種轉錄因子為JUND。在另一實施例中,一或多種轉錄因子為KLF10。在另一實施例中,一或多種轉錄因子為KLF9。在另一實施例中,一或多種轉錄因子為NR1D1。在另一實施例中,一或多種轉錄因子為NR4A1。在另一實施例中,一或多種轉錄因子為TSC22D1。
在另一實施例中,表現載體為病毒載體。
在另一實施例中,表現載體為非病毒載體。
在另一實施例中,表現載體為誘導型表現載體。
在另一實施例中,表現載體包含啟動子,其以可操作方式連接至編碼至少一種轉錄因子之核酸。
在另一實施例中,表現載體包含啟動子,其以可操作方式連接至編碼至少一種轉錄因子之核酸,其中啟動子為內源性啟動子。
在另一實施例中,表現載體包含啟動子,其以可操作方式連接至編碼至少一種轉錄因子之核酸,其中該啟動子為人工啟動子。
在另一實施例中,表現載體包含啟動子,其以可操作方式連接至編碼至少一種轉錄因子之核酸,其中啟動子為誘導型啟動子。
在另一實施例中,增加角膜內皮祖細胞中之至少一種轉錄因子之表現包含誘導角膜內皮祖細胞或神經脊幹細胞中之至少一種轉錄因子之表現。
在另一實施例中,誘導角膜內皮祖細胞或神經脊幹細胞中之至少一種轉錄因子之表現包含使用編碼至少一種轉錄因子之基因開關構築體。
在另一實施例中,誘導角膜內皮祖細胞或神經脊幹細胞中之至少一種轉錄因子之表現包含使用編碼至少一種轉錄因子之基因開關構築體,其中該基因開關構築體為轉錄基因開關構築體。
在另一實施例中,誘導角膜內皮祖細胞或神經脊幹細胞中之至少一種轉錄因子之表現包含使用編碼至少一種轉錄因子之基因開關構築體,其中該基因開關構築體為轉錄後基因開關構築體。
在另一實施例中,用編碼至少一種轉錄因子之病毒載體轉導富潛能幹細胞。
在另一實施例中,用編碼至少一種轉錄因子之表現載體轉染富潛能幹細胞。
在另一實施例中,步驟(a)包含將富潛能幹細胞與小型/母體抗果蠅皮膚生長因子(Small/Mothers Against Decapentaplegic;SMAD)蛋白質信號傳導之至少一種抑制劑一起培養,以誘導富潛能幹細胞分化成角膜內皮祖細胞或神經脊幹細胞。
在另一實施例中,在增加至少一種轉錄因子之表現之前,將角膜內皮祖細胞或神經脊幹細胞培養至少2、3、4、5、6、7、8、9、10、11或12天。
在另一實施例中,在增加至少一種轉錄因子之表現之後,將角膜內皮祖細胞或神經脊幹細胞培養至少8、10、12、14、16、18、20、21、22、23、24、25、26、27、28、29或30天。
在另一實施例中,增加PITX2之表現包含相對於角膜內皮祖細胞或神經脊幹細胞中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,增加FOXC1之表現包含相對於角膜內皮祖細胞或神經脊幹細胞中之FOXC1之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,增加TFAP2B之表現包含相對於角膜內皮祖細胞或神經脊幹細胞中之TFAP2B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,增加LMX1B之表現包含相對於角膜內皮祖細胞或神經脊幹細胞中之LMX1B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,增加POU6F2之表現包含相對於角膜內皮祖細胞或神經脊幹細胞中之POU6F2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞或神經脊幹細胞呈現增加的一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B、LMX1B及MRGPRX3。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞或神經脊幹細胞呈現增加的一或多種選自由以下組成之群的標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B及LMX1B。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞或神經脊幹細胞呈現增加的一或多種選自由以下組成之群之標記物之表現:COL8A1、COL8A2、SLC4A11及MRGPRX3。
在另一實施例中,增加的一或多種標記物之表現包含相對於角膜內皮祖細胞增加至少2倍、5倍、10倍、50倍、100倍、200倍、500倍、1,000倍、2,000倍、5,000倍或10,000倍。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞或神經脊幹細胞呈現降低之NGFR、SOX10、HNK1、SSEA4、NANOG、OCT4、vWF及/或CD31之表現。
在另一實施例中,降低之NGFR、SOX10、HNK1、SSEA4、NANOG、OCT4、vWF及/或CD31之表現包含相對於角膜內皮祖細胞或神經脊幹細胞降低至少0.1倍、0.2倍、0.5倍、1倍、2倍、3倍或4倍。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞呈現以下中之一或多者:增加之泵送功能、增強之緊密接合區形成、增加之對氧化應力之抗性及增加之多邊形形態。
在另一實施例中,增加之泵送功能、增強之緊密接合區形成、增加之對氧化應力之抗性及增加之多邊形形態包含相對於角膜內皮祖細胞增加至少5%、10%、15%、20%或25%。
在另一實施例中,在向有需要之個體之角膜投與角膜內皮細胞後,角膜呈現以下中之一或多者:增加之泵送活性、增加之緊密接合區形成、增加之對氧化應力之抗性、增加之透明度及降低之厚度。
在另一實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本朝向角膜內皮細胞之總轉錄本偏移至少1%、5%、10%、20%、30%、40%或50%。
在另一實施例中,增加至少一種轉錄因子之表現使神經脊幹細胞之總轉錄本朝向角膜內皮細胞之總轉錄本偏移至少1%、5%、10%、20%、30%、40%或50%。
本發明亦提供由本發明之方法產生之角膜內皮細胞群體。
本發明亦提供由包含以下之方法產生之角膜內皮細胞群體:增加角膜內皮祖細胞中之選自由PITX2、FOXC1、TFAP2B、LMX1B及POU6F2組成之群之至少一種轉錄因子之表現,藉此產生角膜內皮細胞。
本發明亦提供藉由包含以下之方法產生之角膜內皮細胞群體:(a)培養富潛能幹細胞及誘導角膜內皮祖細胞之形成,其中富潛能幹細胞包含有包含編碼至少一種選自由以下組成之群之轉錄因子之核酸之表現載體:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2,及(b)增加角膜內皮祖細胞中之來自表現載體之至少一種轉錄因子之表現,藉此產生角膜內皮細胞。
在某些實施例中,PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在某些實施例中,PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
本發明亦提供醫藥組合物,其包含由本發明之方法產生之角膜內皮細胞群體及醫藥學上可接受之載劑。
本發明亦提供醫藥組合物,其包含由包含以下之方法產生之角膜內皮細胞群體及醫藥學上可接受之載劑:增加角膜內皮祖細胞中之至少一種選自由PITX2、FOXC1、TFAP2B、LMX1B及POU6F2組成之群之轉錄因子之表現,藉此產生角膜內皮細胞。
本發明亦提供醫藥組合物,其包含藉由包含以下之方法產生之角膜內皮細胞群體及醫藥學上可接受之載劑:(a)培養富潛能幹細胞及誘導角膜內皮祖細胞之形成,其中富潛能幹細胞包含有包含編碼至少一種選自由以下組成之群之轉錄因子之核酸之表現載體:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2,及(b)增加角膜內皮祖細胞中之來自表現載體之至少一種轉錄因子之表現,藉此產生角膜內皮細胞。
在某些實施例中,PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在某些實施例中,PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
本發明亦提供角膜內皮細胞群體,其包含相對於角膜內皮細胞群體中之轉錄因子之內源性表現量增加的至少一種選自由以下組成之群之轉錄因子之表現量:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
在一個實施例中,角膜內皮細胞為成熟角膜內皮細胞。
在另一實施例中,角膜內皮細胞相對於角膜內皮祖細胞呈現增加的一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B、LMX1B及MRGPRX3。
在某些實施例中,PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在某些實施例中,PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在另一實施例中,角膜內皮細胞群體中之角膜內皮細胞相對於角膜內皮祖細胞呈現增加之一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B及LMX1B。
在另一實施例中,角膜內皮細胞群體中之角膜內皮細胞相對於角膜內皮祖細胞呈現增加之一或多種選自由以下組成之群之標記物之表現:COL8A1、COL8A2、SLC4A11及MRGPRX3。
在另一實施例中,增加之表現包含至少一種轉錄因子之外源性表現。
在另一實施例中,角膜內皮細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體。
在另一實施例中,角膜內皮祖細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體包含自我裂解序列。
在另一實施例中,角膜內皮細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體為病毒載體。
在一個實施例中,病毒載體係選自由以下組成之群:腺相關病毒(AAV)載體、腺病毒載體、慢病毒載體、單純疱疹病毒載體、仙台病毒(sendai virus)載體及反轉錄病毒載體。
在另一實施例中,角膜內皮細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體為非病毒載體。
在一個實施例中,非病毒載體係選自由以下組成之群:質體DNA、線形雙股DNA (dsDNA)、線形單股DNA (ssDNA)、奈米質體、微型環DNA、單股寡脫氧核苷酸(ssODN)、DDNA寡核苷酸、單股mRNA (ssRNA)及雙股mRNA (dsRNA)。
在另一實施例中,非病毒載體包含裸核酸、脂質體、樹枝狀聚合物、奈米粒子、脂質-聚合物系統、固體脂質奈米粒子及/或脂質體魚精蛋白/DNA脂質複合物(LPD)。
在另一實施例中,角膜內皮細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體為誘導型表現載體。
在另一實施例中,角膜內皮細胞包含有包含編碼至少一種轉錄因子之核酸之表現載體,其中該表現載體包含以可操作方式連接至編碼至少一種轉錄因子之核酸之啟動子。
在另一實施例中,啟動子為內源性啟動子。
在另一實施例中,啟動子為人工啟動子。
在另一實施例中,啟動子為誘導型啟動子。
在一個實施例中,轉錄因子為PITX2。
在另一實施例中,增加之PITX2之表現包含相對於角膜內皮細胞群體中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,轉錄因子為FOXC1。
在另一實施例中,增加之FOXC1之表現包含相對於角膜內皮細胞群體中的FOXC1之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,轉錄因子為TFAP2B。
在另一實施例中,增加之TFAP2B之表現包含相對於角膜內皮細胞群體中的TFAP2B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,轉錄因子為LMX1B。
在另一實施例中,增加之LMX1B之表現包含相對於角膜內皮細胞群體中的LMX1B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,轉錄因子為POU6F2。
在另一實施例中,增加之POU6F2之表現包含相對於角膜內皮細胞群體中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
在另一實施例中,角膜內皮細胞群體為成熟角膜內皮細胞群體。
在另一實施例中,角膜內皮細胞係衍生自富潛能幹細胞。
在另一實施例中,富潛能幹細胞為胚胎幹細胞或誘導性富潛能幹細胞。
在另一實施例中,角膜內皮細胞群體包含至少10
6個角膜內皮細胞。
本發明亦提供包含表現載體之富潛能幹細胞,該表現載體包含編碼至少一種選自由以下組成之群之轉錄因子之核酸:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
在某些實施例中,PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在某些實施例中,PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在一個實施例中,表現載體為病毒載體。
在另一實施例中,表現載體為非病毒載體。
在另一實施例中,表現載體為誘導型表現載體。
在另一實施例中,表現載體包含啟動子,其以可操作方式連接至編碼至少一種轉錄因子之核酸。
在另一實施例中,啟動子為內源性啟動子。
在另一實施例中,啟動子為人工啟動子。
在另一實施例中,啟動子為誘導型啟動子。
在另一實施例中,富潛能幹細胞包含編碼至少一種轉錄因子之基因開關構築體。
在另一實施例中,基因開關構築體為轉錄基因開關構築體。
在另一實施例中,基因開關構築體為轉錄後基因開關構築體。
本發明亦提供角膜內皮細胞,其包含有包含編碼至少一種選自由以下組成之群之轉錄因子之核酸之表現載體:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
在某些實施例中,PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在某些實施例中,PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在一個實施例中,角膜內皮細胞為成熟角膜內皮細胞。
在另一實施例中,表現載體為病毒載體。
在另一實施例中,表現載體為非病毒載體。
在另一實施例中,表現載體為誘導型表現載體。
在另一實施例中,表現載體包含啟動子,其以可操作方式連接至編碼至少一種轉錄因子之核酸。
在另一實施例中,啟動子為內源性啟動子。
在另一實施例中,表現載體包含啟動子,其以可操作方式連接至編碼至少一種轉錄因子之核酸,其中該啟動子為人工啟動子。
在另一實施例中,表現載體包含啟動子,其以可操作方式連接至編碼至少一種轉錄因子之核酸,其中該啟動子為誘導型啟動子。
在另一實施例中,富潛能幹細胞包含編碼至少一種轉錄因子之基因開關構築體。
在另一實施例中,富潛能幹細胞包含編碼至少一種轉錄因子之基因開關構築體,其中該基因開關構築體為轉錄基因開關構築體。
在另一實施例中,富潛能幹細胞包含編碼至少一種轉錄因子之基因開關構築體,其中該基因開關構築體為轉錄後基因開關構築體。
本發明亦提供包含本發明之角膜內皮細胞群體、角膜內皮細胞之組合物或角膜內皮細胞之醫藥組合物。
本發明亦提供包含由本發明之方法製備之角膜內皮細胞群體、角膜內皮細胞之組合物或角膜內皮細胞之醫藥組合物。
本發明亦提供用於治療有需要之個體中之疾病之方法,該方法包含向個體投與有效量之根據本發明之角膜內皮細胞群體;包含角膜內皮細胞之組合物;角膜內皮細胞;或包含有角膜內皮細胞群體、包含角膜內皮細胞之組合物或角膜內皮細胞之醫藥組合物,藉此治療個體中之疾病。
本發明亦提供用於治療有需要之個體中之疾病之方法,該方法包含向個體投與有效量之藉由本發明之方法製備之角膜內皮細胞群體;包含角膜內皮細胞之組合物;角膜內皮細胞;或包含有角膜內皮細胞群體、包含角膜內皮細胞之組合物或角膜內皮細胞之醫藥組合物,藉此治療個體中之疾病。
在一個實施例中,疾病係選自由以下組成之群:法曲氏營養不良、虹膜角膜內皮症候群、後部多形性營養不良、先天性遺傳性內皮營養不良、角膜營養不良及角膜移植中之晚期內皮衰竭。
本發明亦提供用於治療有需要之個體之方法,其中該個體呈現引起大皰性角膜病變之角膜水腫之症狀,其中該個體患有由使用隱形眼鏡或白內障手術引起之眼部損傷或其中該個體患有持續性手術創傷,該方法包含向個體投與根據本發明之角膜內皮細胞群體;包含角膜內皮細胞之組合物;角膜內皮細胞;或包含有角膜內皮細胞群體、包含角膜內皮細胞之組合物或角膜內皮細胞之醫藥組合物,藉此治療個體。
本發明亦提供用於治療有需要之個體之方法,其中該個體呈現引起大皰性角膜病變之角膜水腫之症狀,其中該個體患有由使用隱形眼鏡或白內障手術引起之眼部損傷或其中該個體患有持續性手術創傷,該方法包含向個體投與有效量之藉由本發明之方法製備之角膜內皮細胞群體;包含角膜內皮細胞之組合物;角膜內皮細胞;或包含有角膜內皮細胞群體、包含角膜內皮細胞之組合物或角膜內皮細胞之醫藥組合物,藉此治療個體。
本發明亦提供套組,其包含根據本發明之包含角膜內皮細胞群體之組合物;包含角膜內皮細胞之組合物;角膜內皮細胞;或包含有角膜內皮細胞群體、包含角膜內皮細胞之組合物或角膜內皮細胞之醫藥組合物。
本發明亦提供套組,其包含根據本發明之方法製備之包含角膜內皮細胞群體之組合物;包含角膜內皮細胞之組合物;角膜內皮細胞;或包含有角膜內皮細胞群體、包含角膜內皮細胞之組合物或角膜內皮細胞之醫藥組合物。
在一個實施例中,套組包含表現載體,該表現載體包含編碼至少一種選自由以下組成之群之轉錄因子之核酸:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
在某些實施例中,PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在某些實施例中,PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。在某些實施例中,POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
本發明亦提供套組,其包含至少一種選自由以下組成之群之轉錄因子:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
藉由以下詳細說明及圖式進一步說明本發明。
相關申請案
本申請案主張2021年5月3日提交之名稱為「METHODS OF GENERATING MATURE CORNEAL ENDOTHELIAL CELLS」之美國臨時申請案第63/183,562號在35 U.S.C. § 119(e)下之權利。
本發明提供可行及有效的用於產生CEC,例如成熟CEC之方法。該等方法包括增加角膜內皮祖細胞或富潛能幹細胞(例如,誘導性富潛能幹細胞或胚胎幹細胞)中之至少一種選自由以下組成之群之轉錄因子之表現,藉此產生CEC,例如成熟CEC:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。本發明亦提供藉由此等方法產生之組合物及使用此等組合物之方法。CEC,例如成熟CEC,係經由富潛能或多潛能幹細胞之定向分化而產生,該等幹細胞包括人類誘導性富潛能幹細胞(hiPSC)、人類胚胎幹細胞(hESC)及體細胞(包括經轉分化之細胞及幹細胞,諸如神經脊幹細胞)。本發明之方法為可行及有效的,且引起產生可用於本文中所揭示之各種應用(例如,治療眼部疾病,例如角膜之疾病)之CEC,例如成熟CEC。預期此等細胞可提供用於治療用途之難以收集的供給角膜之替代物。
以下詳細說明揭示如何製備及使用本發明。
為了使本發明可更易於理解,首先對某些術語進行定義。亦應注意,不論何時敍述參數之值或值之範圍,意欲所述值之範圍內的值及範圍亦為本發明之一部分。
在以下描述中,出於說明之目的,闡述特定數量、材料及組態以便提供對本發明之透徹理解。然而,一般熟習此項技術者將顯而易見,本發明可在無此等特定細節之情況下實踐。在一些情況下,可省略或簡化熟知的特徵以免混淆本發明。此外,說明書中提及諸如「一個實施例」或「一實施例」之片語意謂結合實施例所描述之特定特性、結構或特徵包括於本發明之至少一個實施例中。說明書中多處出現的諸如「在一個實施例中」之片語未必皆指同一實施例。
定義
除非另外規定,否則以下術語中之每一者具有此章節中所闡述之含義。
不定冠詞「一(a/an)」係指相關名詞中之至少一者,且可與術語「至少一個」及「一或多個」互換使用。
連詞「或」及「及/或」可與非排他性分離詞(disjunction)互換地使用。
根據本申請案,術語「約」意謂參考值之+/-5%。
「角膜內皮細胞」或「CEC」通常係指在角膜之後表面上排列且面向眼睛之前房的富含粒線體之細胞(在活機體中)。CEC亦可使用本文中所描述之方法自另一種細胞類型產生,例如藉由神經脊幹細胞、胚胎幹細胞(ESC)或誘導性富潛能幹細胞(iPSC)之分化。自NCSC、ES細胞或iPS細胞分化之CEC可由其呈現內源性CEC之一或多種屬性來鑑別或識別,該一或多種屬性諸如CEC標記物之表現;形成具有明顯的六邊形形狀之大小均勻的細胞之單層之能力;形成允許溶質及營養物自眼房液滲漏至角膜之更淺的表層,同時以相反方向(自基質至眼房液)主動泵送水之「滲漏泵」之能力。例示性CEC標記物包括(但不限於):Na+/K+ ATP酶、ZO-1、KLF13、AQP1、膠原蛋白VIII、SLC16A3、CFTR、NBC1、CA2、AE2 SCL4A2、SCL16A1、CA12、CA4、FOXC1。舉例而言,CEC通常表現膠原蛋白VIII、Na+K+ ATP酶泵及ZO-1,且不表現vWF及CD31 (後者存在於血管內皮細胞中)。此外,CEC可表現一或多種角膜內皮泵標記物(其包括:Na+/K+ ATP酶、SLC4A4、SLC4A11、AQP1、CA2、CA4、CA12、SCL14A2、SLC16A1、SLC16A3、SLC16A7、CFTR、NHE1、ADCY10、電壓依賴性陰離子通道VDAC2及VDAC3、氯離子通道蛋白質CLCN2及CLC)、眼周神經脊標記物(其包括:PITX2及FOXC1)及/或細胞黏附及基質蛋白(其包括:緊連蛋白(Occludin)、連結蛋白(Connexin) 43、9.3E抗原、膠原蛋白III、膠原蛋白IV、N鈣黏素、VE鈣黏素、E鈣黏素、β連環蛋白、p120、p190層黏連蛋白α4、巢蛋白-2及軸突引導因子4)。舉例而言,CEC可表現至少一種角膜內皮泵標記物、至少一種眼周神經脊標記物以及至少一種細胞黏附及基質蛋白。角膜內皮細胞包括如本文中所定義之成熟角膜內皮細胞。
在另一實施例中,CEC顯示指示CEC成熟之整體基因表現圖譜。藉由此項技術中已知之任何方法(例如轉錄組學分析或微陣列分析)獲得整體基因表現圖譜。
如本文中所使用之術語「成熟角膜內皮細胞」或「成熟CEC」係指呈現與成熟表現型相關之標記物之CEC,該等標記物包括COL8A1、COL8A2、SLC4A11及MRGPRX3中之一或多者。成熟CEC形成具有明顯六邊形或多邊形形態之大小均勻的細胞之單層,其中細胞呈現彼此之間的緊密黏附及形成緊密接合區之能力,該等緊密接合區形成維持基質脫水之障壁。部分歸因於成熟CEC彼此之間的緊密黏附、形成緊密接合區之能力、細胞之間的緊密接合區之數目及調節角膜內皮泵之蛋白質之表現,成熟CEC呈現高水準的泵送功能。緊密接合區形成障壁以減少流入基質之水且經改良之泵活性可促進維持角膜中之適當流體水準。成熟角膜內皮細胞亦可呈現對氧化應力之抗性。成熟角膜內皮細胞可表現與泵送功能相關之標記物,例如SLC4A11及SLC4A4。成熟角膜內皮細胞中可表現之其他與泵送功能相關之標記物包括Na+/K+ ATP酶、AQP1、CA2、CA4、CA12、SCL14A2、SLC16A1、SLC16A3、SLC16A7、CFTR、NHE1、ADCY10、電壓依賴性陰離子通道VDAC2及VDAC3、氯離子通道蛋白質CLCN2及CLC。
成熟CEC可呈現活體內功效,舉例而言,在將成熟角膜內皮細胞移植至患有角膜病症之個體中之後,可將成熟角膜內皮細胞植入受體角膜上且形成細胞之單層,其中該等細胞形成緊密接合區。可使用熟習此項技術者已知的方法實現移植。舉例而言,可使用利用生物材料之經生物工程改造之角膜移植物來實現移植(參見例如2019年4月11日申請之PCT公開案第WO 2019/198086號)。由於形成緊密接合區及表現與泵送功能相關之標記物,活體內成熟CEC可改良受體角膜之泵送功能,引起角膜之透明度增加。所移植的成熟CEC亦可降低受體角膜之厚度且增加受體角膜之透明度。成熟角膜內皮細胞中可表現之其他標記物包括(但不限於) PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B、LMX1B、AQP1、ATP1A1、TJP1、NCAM1、CDH2、SLC4A4、CD166、POU6F2、CD248及MRGPRX3。在一個實施例中,成熟角膜內皮細胞中表現之標記物為PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2b、LMX1B及MRGPRX3。在一個實施例中,成熟角膜內皮細胞中表現之標記物為PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B及LMX1B。在一個實施例中,成熟角膜內皮細胞中表現之標記物為COL8A1、COL8A2、SLC4A11及MRGPRX3。
「神經脊幹細胞」或「NCSC」通常係指具有產生各種細胞類型之發育潛力之神經祖細胞,該等細胞類型諸如黑色素細胞、顱面骨骼、周邊神經系統、神經膠質、平滑肌、角化細胞及角膜內皮。神經脊幹細胞可自iPSC或hES細胞分化,例如使用如本文中所描述或如WO/2010/096496或U.S. 9,752,118中所描述之雙重SMAD抑制劑,其各自以全文引用之方式併入本文中。神經脊幹細胞可使用Wnt促效劑(諸如Wnt3a及/或(2'Z,3'E)-6-溴靛玉紅至3'-肟(BIO))及SMAD抑制劑(諸如SB431542及/或諾金)之組合自hES細胞或iPSC分化;參見Menendez等人, PNAS, 2011年11月29日, 第108卷, 第48號, 19240-19245。舉例而言,在hESC與SB431542及BIO (在存在或不存在諾金之情況下)或與Wnt3a及SB431542接觸之後報導NCSC之有效誘導。NCSC亦可自神經玫瑰結(neural rosettes)之培養物獲得,例如藉由在MS5基質飼養細胞上培養hES細胞(參見Lee等人, Stem Cells 25 (8), 1931-1393 (2007),其以全文引用之方式併入本文中)。NCSC亦可自許多組織獲得,包括在正在發育的胚胎中,在神經管、坐骨神經、消化道及背根節中;及在青少年及成年人中,在背根節、骨髓、皮膚、心臟、角膜、牙齒及頸動脈體中。參見Nagoshi等人, Journal of Cellular Biochemistry 107:1046-1052 (2009);Crane及Trainor, Annu. Rev. Cell Dev. Biol. 2006. 22:267-86;及Blum, Brain Research Bulletin 83 (2010) 189-193,其各自以全文引用之方式併入本文中。
可藉由本文中鑑別及此項技術中已知的標記物之表現鑑別神經脊幹細胞。例示性神經脊幹細胞標記物包括(但不限於):SOX10、AP2、HNK1、PAX3、PAX7及p75 (NGFR),以及低或不存在Pax6表現。眼周間質(POM)為對PITX2及FOXC1呈陽性之神經脊細胞之亞群,其亦可表現TFAP2B及/或LMX1B。
術語「角膜內皮祖細胞」通常係指後神經脊階段細胞,其開始獲取CEC之一些特徵,諸如早期至中期CEC標記物(ZO1、Na+/K+ ATP酶、N-鈣黏素、NCAM1、CD166、PITX2、FOXC1、COL8A1、TFAP2B、SLC4A4)之表現,及形成多邊形或六邊形細胞之單層之能力。此等細胞未必以與成熟CEC相等之水準或以與成熟CEC相同的表現水準百分比來表現CEC標記物。
如本文中所使用,術語「標記物」或「細胞標記物」係指其存在可鑑別特定細胞或細胞類型之基因(例如,以RNA形式)或蛋白質。細胞之標記物可不限於一種標記物,標記物可指標記物之「模式」,使得指定的標記物組可區分一種細胞或細胞類型與另一種細胞或細胞類型,例如包括一些標記物之表現且不存在或存在較低的指示其他細胞類型之其他標記物之表現之模式。舉例而言,CEC群體(例如成熟CEC)可對CEC (例如成熟CEC)之標記物呈陽性且對指示其他細胞類型之標記物呈陰性,諸如不存在表現於其他內皮細胞類型上之標記物、不存在由hES細胞或iPSC表現之標記物及/或不存在由神經脊幹細胞表現之標記物。此外,當藉由細胞染色方法(例如,免疫螢光及其類似方法)偵測到標記物表現時,可鑑別細胞對提供所預期的染色模式(諸如標記物ZO-1之緊密接合區定位)之特定標記物呈陽性。可藉由此項技術中已知的任何方法偵測標記物之表現,包括(但不限於):西方墨點法(Western blotting)、基於mRNA擴增之方法(例如,PCR、等溫擴增等,其可包括反轉錄且可用於偵測來自單一細胞或多種細胞之表現)、北方墨點法(Northern blotting)、免疫染色等。此外,可由受基因元件控制之報導子構築體(諸如,螢光蛋白,其表現可以目視方式偵測;抗生素抗性基因,其表現可藉由在存在抗生素之情況下之細胞存活率來偵測等)之表現來推斷該等標記物之表現,該基因元件賦予細胞類型特異性表現,諸如一種前述標記物或其片段之啟動子。來自文獻之例示性報導子構築體為pOCT4-GFP及pOCT4-LUC基因,其分別驅動ES細胞中之GFP及螢光素酶之表現,其表現皆可使用習知方法容易地偵測。其他可使用的偵測標記物表現之方法為此項技術中已知的。通常參見Ausubel, Current Protocols in Molecular Biology (Current Protocols, 1988);Ausubel等人, Short Protocols in Molecular Biology (Current Protocols; 第5版, 2002);Sambrook等人, Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 第3版, 2001);Sambrook等人, The Condensed Protocols from Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 2006),其各自以全文引用之方式併入本文中。
如本文中所使用,「增加」或「增加的」在其指表現或活性之水準時意謂與對照性表現或活性之水準相比增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、3倍、4倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。「增加」在其指表現或活性之水準時亦意謂與對照性表現或活性之水準相比增加至少5%、10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、79%、75%、80%、85%、90%、95%或100%。
如本文中所使用,術語「增加表現」係指相對於轉錄因子之內源性核酸水準及/或蛋白質水準,增加編碼本文中所揭示之轉錄因子之核酸(例如,RNA或DNA)之水準及/或活性及/或增加本文中所揭示之轉錄因子之水準及/或活性。在一些實施例中,增加至少一種轉錄因子之表現包含使細胞(例如,角膜內皮祖細胞或富潛能幹細胞,例如胚胎幹細胞或誘導性富潛能幹細胞)與至少一種轉錄因子接觸。在一些實施例中,增加至少一種轉錄因子之表現包含用編碼至少一種轉錄因子之病毒載體轉導細胞(例如,角膜內皮祖細胞或富潛能幹細胞,例如胚胎幹細胞或誘導性富潛能幹細胞)。在一些實施例中,增加至少一種轉錄因子之表現包含用編碼至少一種轉錄因子之表現載體轉染細胞(例如,角膜內皮祖細胞或富潛能幹細胞,例如胚胎幹細胞或誘導性富潛能幹細胞)。
在一些實施例中,增加至少一種轉錄因子之表現包含相對於細胞(例如,角膜內皮祖細胞或富潛能幹細胞,例如胚胎幹細胞或誘導性富潛能幹細胞)中之至少一種轉錄因子之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。在一些實施例中,增加至少一種轉錄因子之表現包含相對於細胞(例如,角膜內皮細胞或富潛能幹細胞,例如胚胎幹細胞或誘導性富潛能幹細胞)中之至少一種轉錄因子之內源性表現量增加至少5%、10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%、85%、90%、95%、100%、150%、200%、300%、400%、500%或1000%。
如本文中所使用,「降低」或「降低的」在其指表現或活性之水準時意謂與對照性表現或活性之水準相比降低至少0.1倍、0.2倍、0.5倍、1倍、2倍、3倍、4倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。「降低」在其指表現或活性之水準時亦意謂與對照性表現或活性之水準相比降低至少5%、10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、79%、75%、80%、85%、90%、95%或100%。
本發明之各種方法包括涉及與對照物比較值、水準、特性、特徵、及/或性質之步驟。「對照物」可為一般熟習此項技術者熟悉的適用於比較目的之任何對照物或標準。在一個實施例中,「對照物」為在增加如本文中所描述之細胞(例如,富潛能幹細胞、角膜內皮祖細胞、CEC,例如成熟CEC)中之轉錄因子之表現之前測定的值、水準、特性、特徵、性質等。舉例而言,可在細胞中表現轉錄因子之前或在不存在轉錄因子之情況下測定轉錄因子之表現量、CEC譜系之細胞(CEC)之標記物(例如,成熟CEC活性或形態,例如泵送功能、對氧化應力之抗性或細胞群體中之緊密接合區形成)之表現量。在另一實施例中,「對照物」為在呈現例如正常特性之細胞或生物體(例如,對照性或正常細胞或生物體)中測定之值、水準、特性、特徵、性質等。在另一實施例中,「對照物」為在轉錄因子之表現之前測定的預定值、水準、特性、特徵、性質等。在另一實施例中,「對照物」意謂可作為CEC,例如成熟CEC之對照物之角膜內皮祖細胞。
「對照細胞」可指與表現轉錄因子之細胞進行比較之細胞。「對照細胞」可不表現轉錄因子。「對照細胞」與使用其作為對照物之細胞相比可在不同條件(包括劑量、時間長度等)下與表現轉錄因子之表現載體接觸。
如本文中所使用,術語「內源性」係指核酸、多核苷酸、寡核苷酸、DNA、RNA、基因、肽或多肽在其位於細胞或細胞之基因體中之天然位置處之原生形式。
如本文中所使用,「外源性」係指來源於細胞外部或細胞之基因體外部之核酸、多核苷酸、寡核苷酸、DNA、RNA、基因、肽或多肽。
如本文中所使用,術語「成熟」係指細胞(例如,角膜內皮祖細胞)變得特殊化程度及/或功能性更高(例如,與其活體內功能狀態類似)所需之過程。在一個實施例中,角膜內皮祖細胞變成CEC,例如成熟CEC之過程稱為成熟。
如本文中所使用,術語「富潛能幹細胞」、「PS細胞」或「PSC」包括胚胎幹細胞、誘導性富潛能幹細胞及胚胎衍生之富潛能幹細胞,與用於衍生富潛能幹細胞之方法無關。在功能上將富潛能幹細胞定義為滿足以下條件之幹細胞::(a)當在免疫缺乏(SCID)小鼠中移植時能夠誘發畸胎瘤;(b)能夠分化成所有三種胚層之細胞類型(例如,可分化成外胚層、中胚層及內胚層細胞類型);(c)表現胚胎幹細胞之一或多種標記物(例如,表現OCT4、鹼性磷酸酶、SSEA-3表面抗原、SSEA-4表面抗原、NANOG、TRA-1-60、TRA-1-81、SOX2、REX1等);及(d)能夠自我更新。術語「富潛能」係指細胞形成身體或軀體(亦即,胚體)之所有譜系的能力。舉例而言,胚胎幹細胞及誘導性富潛能幹細胞為一種能夠自三個胚層:外胚層、中胚層及內胚層中之每一者形成細胞的富潛能幹細胞。多能性為發育效能之連續體,其範圍介於不能產生完全生物體之不完全或部分富潛能細胞至能夠產生完全生物體之更原始、更富潛能的細胞(例如,胚胎幹細胞)。可使用例如此項技術中已知之方法產生例示性富潛能幹細胞。例示性富潛能幹細胞包括(但不限於)衍生自囊胚期胚胎之內細胞團的胚胎幹細胞、衍生自卵裂期或桑椹胚期胚胎之一或多種分裂球的胚胎幹細胞(視情況在不破壞胚胎之其餘部分之情況下)、藉由將體細胞重編程為富潛能狀態而產生的誘導性富潛能幹細胞及由胚胎生殖(EG)細胞產生的富潛能細胞(例如,藉由在存在FGF-2、LIF及SCF之情況下培養)。此類胚胎幹細胞可自藉由授精或藉由無性方式產生之胚胎材料產生,無性方式包括體細胞核轉移(somatic cell nuclear transfer;SCNT)、孤雌生殖及雄核生殖。
在一個實施例中,富潛能幹細胞可經基因工程改造或以其他方式經修飾例如以增加壽命、效能、導向;預防或降低免疫反應;或遞送自此類富潛能細胞(例如,角膜內皮細胞)獲得之細胞中之所需因子。舉例而言,富潛能幹細胞且因此,所得分化細胞可經工程改造或以其他方式經修飾以不具有或具有降低之β2微球蛋白、I類基因(包括HLA-A、HLA-B、HLA-C、HLA-E、HLA-F及HLA-G)、TAP1、TAP2、甲巰蛋白、CTIIA、RFX5、TRAC或TRAB基因之表現。如以全文引用之方式併入本文中的WO2012145384及WO2013158292中所描述,在一些實施例中,細胞(諸如富潛能幹細胞及所得分化細胞,諸如成熟CEC)包含β-2微球蛋白(B2M)基因中之經基因工程改造之破壞。在一些實施例中,細胞進一步包含能夠編碼單鏈融合人類白血球抗原(HLA)I類蛋白質之多核苷酸,該蛋白質包含直接或經由連接子序列共價連接至HLA-1α鏈之至少一部分的B2M蛋白之至少一部分。在一些實施例中,HLA-1α鏈係選自HLA-A、HLA-B、HLA-C、HLA-E、HLA-F及HLA-G。在一些實施例中,細胞包含人類白血球抗原(HLA)II類相關基因中之經基因工程改造之破壞。在一些實施例中,HLA II類相關基因係選自含有調節因子X相關錨蛋白之蛋白質(RFXANK)、調節因子5 (RFX5)、調節因子X相關蛋白(RFXAP)、II類反式活化因子(CIITA)、HLA-DPA (α鏈)、HLA-DPB (β鏈)、HLA-DQA、HLA-DQB、HLA-DRA、HLA-DRB、HLA-DMA、HLA-DMB、HLA-DOA及HLA-DOB。在一些實施例中,細胞包含一或多種編碼單鏈融合HLA II類蛋白或HLA II類蛋白之多核苷酸。
富潛能幹細胞及所得分化細胞可經工程改造或以其他方式經修飾以增加基因之表現。在一個實施例中,富潛能幹細胞可經工程改造以表現一或多種本發明之轉錄因子或增加其表現。存在多種用於工程改造細胞以調節一或多種基因(或蛋白質)之表現之技術,包括使用病毒載體,諸如AAV載體;鋅指核酸酶(ZFN);轉錄活化因子樣效應物核酸酶(TALEN);及用於基因體工程改造之基於CRISPR/Cas之方法;以及使用轉錄及轉譯抑制劑,諸如反義及RNA干擾(其可使用穩定整合之載體及游離基因組載體來實現)。
術語「胚胎」或「胚胎型」意謂尚未植入母體宿主之子宮膜中之正在發育的細胞塊。「胚胎細胞」為自胚胎分離或胚胎中所含的細胞。此細胞亦包括早在二細胞階段獲得之分裂球及在提取後聚集的分裂球。
如本文中所使用,術語「胚胎衍生之細胞」(EDC)廣泛地指桑椹胚衍生之細胞、囊胚衍生之細胞(包括內細胞團、胚盾或上胚層之細胞)或早期胚胎之其他富潛能幹細胞(包括原始內胚層、外胚層及中胚層以及其衍生物)。「EDC」亦包括分裂球及來自聚集的單一分裂球之細胞塊或來自不同發育期之胚胎,但不包括已以細胞株形式傳代之人類胚胎幹細胞。
如本文中所使用,術語「胚胎幹細胞」、「ES細胞」或「ESC」廣泛地指自囊胚或桑椹胚之內細胞團分離且以細胞株形式連續傳代之細胞。該術語亦包括自胚胎之一或多個分裂球分離(較佳不破壞胚胎之其餘部分)之細胞(參見例如Chung等人, Cell Stem Cell. 2008年2月7日;2(2): 1 13-7;美國公開案第20060206953號;美國公開案第2008/0057041號,其各自以全文引用之方式併入本文中)。ES細胞可由卵細胞被精子或DNA授精、核轉移、孤雌生殖或藉由任何用於產生在HLA區域中具有純合性之ES細胞之手段而獲得。ES細胞亦可指由精子及卵細胞之融合、核轉移、孤雌生殖或染色質之重編程及隨後將重編程染色質併入質膜以產生細胞而產生的接合子、分裂球或囊胚期哺乳動物胚胎獲得的細胞。在一個實施例中,胚胎幹細胞可為人類胚胎幹細胞(或「hES細胞」)。在一個實施例中,人類胚胎幹細胞並非自授精超過14天之胚胎獲得。在另一實施例中,人類胚胎幹細胞並非自活體內發育之胚胎獲得。在另一實施例中,自藉由活體外授精產生之植入前胚胎獲得人類胚胎幹細胞。
如本文中所使用,「誘導性富潛能幹細胞」或「iPS細胞」或「iPSC」通常係指由重編程體細胞獲得之富潛能幹細胞。iPS細胞可藉由在體細胞中表現或誘導表現各因子(「重編程因子」)之組合而生成,該等因子例如OCT4 (有時稱為Oct 3/4)、SOX2、MYC (例如c-MYC或任何MYC變異體)、NANOG、LIN28及KLF4。在一個實施例中,重編程因子包含OCT4、SOX2、c-MYC及KLF4。在另一實施例中,重編程因子包含OCT4、SOX2、NANOG及LIN28。在某些實施例中,在體細胞中表現至少兩種重編程因子,以成功地重編程體細胞。在其他實施例中,在體細胞中表現至少三種重編程因子,以成功地重編程體細胞。在其他實施例中,在體細胞中表現至少四種重編程因子,以成功地重編程體細胞。在另一實施例中,在體細胞中表現至少五種重編程因子,以成功地重編程體細胞。在另一實施例中,在體細胞中表現至少六種重編程因子,例如OCT4、SOX2、c-MYC、NANOG、LIN28及KLF4。在其他實施例中,鑑別其他重編程因子且單獨使用或與一或多種已知的重編程因子組合使用,以將體細胞重編程為富潛能幹細胞。
可使用胎兒、產後、新生兒、青少年或成人體細胞產生iPS細胞。體細胞可包括(但不限於)成纖維細胞、角質細胞、脂肪細胞、肌肉細胞、器官及組織細胞,以及各種血液細胞,包括(但不限於)造血細胞(例如,造血幹細胞)。在一個實施例中,體細胞為成纖維細胞,諸如真皮成纖維細胞、滑膜成纖維細胞、或肺成纖維細胞,或非成纖維細胞型體細胞。
可自細胞庫獲得iPS細胞。或者,可藉由此項技術中已知的方法新產生iPS細胞。可使用來自特定患者或匹配供體之材料來特異性產生iPS細胞,從而產生組織匹配的細胞。在一個實施例中,iPS細胞可為實質上不具有免疫原性之通用供體細胞。
可藉由在體細胞中表現或誘導表現一或多種重編程因子來產生誘導性富潛能幹細胞。可藉由使用病毒載體(諸如(但不限於)慢病毒載體或反轉錄病毒載體)感染或使用其他基因編輯技術(諸如CRISPR、Talen、鋅指核酸酶(ZFN)),在體細胞中表現重編程因子。此外,可使用非整合載體(諸如游離基因組質體)或RNA (諸如合成mRNA)或經由RNA病毒(諸如仙台病毒)在體細胞中表現重編程因子。當使用非整合載體表現重編程因子時,可使用載體對體細胞進行電穿孔、轉染或轉型,而在細胞中表現該等因子。舉例而言,在小鼠細胞中,使用整合病毒載體之四種因子(OCT3/4、SOX2、c-MYC及KLF4)之表現即足以重編程體細胞。在人類細胞中,使用整合病毒載體之四種因子(OCT3/4、SOX2、NANOG及LIN28)之表現即足以重編程體細胞。
可藉由使體細胞與至少一種誘導重編程因子之表現之試劑(諸如小型有機分子試劑)接觸來誘導重編程因子之表現。
體細胞亦可使用其中表現重編程因子(例如,使用病毒載體、質體及其類似物)及誘導重編程因子之表現(例如,使用小型有機分子)之組合方法重編程。
在細胞中表現或誘導重編程因子後,可培養細胞。隨時間推移,培養皿中出現具有ES特徵之細胞。可基於例如ES細胞形態或基於可選擇或可偵測標記物之表現來選擇及繼代培養細胞。可培養細胞以產生與ES細胞類似之細胞之培養物。
為了確認iPS細胞之富潛能性,可在一或多種富潛能性分析法中測試細胞。舉例而言,可測試細胞之ES細胞標記物之表現;可評估細胞在移植至SCID小鼠中時產生畸胎瘤的能力;可評估細胞分化以產生所有三種胚層之細胞類型的能力。
iPS細胞可來自任何物種。此等iPS細胞已使用小鼠及人類細胞成功地產生。此外,已使用胚胎、胎兒、新生兒及成人組織成功地產生iPS細胞。因此,可使用來自任何物種之供體細胞容易地產生iPS細胞。因此,可自任何物種產生iPS細胞,包括(但不限於)人類、非人類靈長類動物、嚙齒類動物(小鼠、大鼠)、有蹄類動物(牛、羊等)、犬(家養及野生犬)、貓科動物(家養及野生貓科動物,諸如獅子、老虎、獵豹)、兔、倉鼠、山羊、大象、熊貓(包括大熊貓)、豬、浣熊、馬、斑馬、海洋哺乳動物(海豚、鯨等)及其類似物。
如本文中所使用,「有效量」廣泛地指在投與患者以用於治療疾病時足以實現此類疾病之治療的化合物或細胞之量。有效量可為有效實現防治之量及/或有效實現預防之量。有效量可為可有效實現緩解之量、有效實現以下目的之量:預防病徵/症狀之發生、降低病徵/症狀之發生之嚴重程度、消除病徵/症狀之發生、減緩病徵/症狀之發生之發展、預防病徵/症狀之發生之發展及/或實現病徵/症狀之發生之防治。「有效量」可視疾病及其嚴重程度以及所治療之患者之年齡、體重、醫療史、敏感性及先前存在的病狀而變化。在本發明中,術語「有效量」與「治療有效量」具有相同含義。
術語「接觸」(例如,使細胞(諸如角膜內皮祖細胞或富潛能幹細胞,例如胚胎幹細胞或誘導性富潛能幹細胞)與根據本發明之轉錄因子接觸)意欲包括任何用於將轉錄因子引入細胞及/或活體外共同培育轉錄因子及細胞之方法(例如,將轉錄因子添加至培養物中之細胞中)。在一些實施例中,術語「接觸」並不意欲包括細胞在活體內暴露於可能天然存在於個體中之如本文中所揭示之轉錄因子。可以任何適合的方式進行使細胞與如本文中所揭示之轉錄因子接觸之步驟。可在貼壁培養物或懸浮培養物中處理細胞,且可實質上同時(例如,共同以混合物形式)或依序(例如,與第一轉錄因子之添加間隔1小時、1天或更長時間以內)添加轉錄因子。應理解,與如本文中所揭示之轉錄因子接觸的細胞亦可同時或接著與另一試劑,諸如生長因子或其他分化試劑或環境接觸,以使細胞穩定或使細胞進一步分化。在一個實施例中,使細胞與轉錄因子接觸包括用包含編碼轉錄因子之核酸的載體轉導細胞或用包含編碼轉錄因子之核酸的表現載體轉染細胞,且可包括在此項技術中已知(例如用於培養富潛能及/或分化細胞)的條件下培養細胞,例如實施例中進一步描述。
「接觸」亦指使細胞(例如,富潛能幹細胞、角膜內皮祖細胞、神經脊幹細胞、CEC,例如成熟CEC)與調節表現轉錄因子之誘導型表現載體之表現之試劑(例如,活化/誘導來自包含誘導型啟動子之載體或包含基因開關之載體之轉錄因子之表現之試劑,例如小分子試劑)接觸。
術語「接觸」(例如,使角膜內皮祖細胞或富潛能幹細胞與根據本發明之轉錄因子接觸)意欲包括任何用於將轉錄因子引入角膜內皮祖細胞或富潛能幹細胞中及/或在活體外共同培育轉錄因子及角膜內皮祖細胞或富潛能幹細胞之方法(例如,向培養物中之細胞中添加轉錄因子)。在一些實施例中,術語「接觸」並不意欲包括角膜內皮祖細胞或富潛能幹細胞活體內暴露於可天然存在於個體中之如本文中所揭示之轉錄因子。可以任何適合的方式進行使角膜內皮祖細胞或富潛能幹細胞與如本文中所揭示之轉錄因子接觸之步驟。可在貼壁培養物或懸浮培養物中處理細胞,且可實質上同時(例如,共同以混合物形式)或依序(例如,與第一轉錄因子之添加間隔1小時、1天或更長時間以內)添加轉錄因子。應理解,與如本文中所揭示之轉錄因子接觸的細胞亦可同時或接著與另一試劑,諸如生長因子或其他分化試劑或環境接觸,以使細胞穩定或使細胞進一步分化。在一個實施例中,使角膜內皮祖細胞或富潛能幹細胞與轉錄因子包括用包含編碼轉錄因子之核酸之載體轉導角膜內皮祖細胞或富潛能幹細胞,或用包含編碼轉錄因子之核酸之表現載體轉染角膜內皮祖細胞或富潛能幹細胞,且可包括在此項技術中已知(例如,用於培養分化細胞)的條件下培養細胞,例如實例中進一步描述。
如本文中所使用,術語「分化」為未特化(「未定型」)或特化程度較低的細胞獲得特化細胞(諸如CEC,例如成熟CEC)之特徵的過程。分化細胞為在細胞譜系中佔據更特殊位置的細胞。舉例而言,iPSC或hES細胞可分化成各種分化程度較高的細胞類型,包括CEC,例如成熟CEC。在某些實施例中,在活體外進行細胞之分化且排除活體內分化。
如本文中所使用,術語「經培養」或「培養」係指將細胞置放於尤其含有維持所培養之細胞之生命所需的營養物(包括任何指定的添加物)之培養基中。當用於維持細胞之培養基含有指定物質時,此類細胞係「在存在此類指定物質之情況下」培養。培養可在其中細胞可保持暴露於培養基之任何容器或設備中進行,包括(但不限於)皮氏培養皿(petri dish)、培養皿(culture dish)、血液收集袋、滾瓶、培養瓶、試管、微量滴定孔、中空纖維筒或此項技術中已知的任何其他設備。
如本文中所使用,術語「繼代培養」或「傳代」係指將來自先前培養物之一些或所有細胞轉移至新鮮的生長培養基及/或塗佈於新的培養皿上且進一步培養細胞。可進行繼代培養例如以延長壽命、富集所需細胞群體及/或擴增培養物中之細胞之數目。舉例而言,該術語包括以較低細胞密度將一些或所有細胞轉移、培養或塗佈至新的培養容器以允許細胞增殖。
如本文中所使用,「投藥」、「投與」及其變異形式係指將組合物或藥劑引入個體且包括同時及依序引入組合物或藥劑。「投藥」可指例如治療、藥物動力學、診斷、研究、安慰劑以及實驗方法。「投藥」亦涵蓋活體外及離體治療。投藥包括自行投藥及由另一者投藥。可藉由任何適合的途徑進行投藥。適合的投藥途徑允許組合物或藥劑發揮其所欲功能。舉例而言,若適合的途徑為靜脈內,則藉由將組合物或藥劑引入個體之靜脈來投與組合物。
如本文中所使用,術語「個體(subject/individual)」、「宿主」及「患者」在本文中可互換使用,且係指需要診斷、治療或療法之任何哺乳動物個體,尤其人類。本文中所描述之方法適用於人類療法及獸醫學應用。在一些實施例中,個體為哺乳動物,且在特定實施例中,個體為人類。
如本文中所使用,術語活性劑(例如,CEC,例如成熟CEC)之「治療量」、「治療有效量」、「有效量」或「醫藥學上有效量」可互換地用於指足以提供所欲治療益處之量。然而,劑量水準係基於各種因素,包括損傷類型、患者之年齡、體重、性別、醫學狀況、病狀之嚴重程度、投藥途徑、預期的細胞移植、長期存活期及/或所使用之特定活性劑。因此,給藥方案可廣泛變化,但可常規地由醫師使用標準方法確定。此外,術語「治療量」、「治療有效量」及「醫藥學上有效量」包括所描述發明之組合物之防治或預防量。在所描述發明之防治或預防應用中,以足以消除或降低風險、減輕嚴重程度或延遲疾病、病症或病狀發作之量,向容易發生該疾病、病症或病狀或處於其風險下之患者投與醫藥組合物或藥劑,包括該疾病、病症或病狀之生物化學、組織學及/或行為症狀、其併發症及在該疾病、病症或病狀發展期間呈現之中間病理性表現型。通常較佳的是,使用最大劑量,亦即,根據一些醫學判斷之最高安全劑量。術語「劑量(dose/dosage)」在本文中可互換使用。
如本文中所使用,術語「治療作用」係指治療之結果,其結果判定為所期望的且有益的。治療作用可包括直接地或間接地抑制、減少或消除疾病表現。治療作用亦可包括直接地或間接地抑制、減少或消除疾病表現之發展。
對於本文中所描述之治療劑(例如,CEC,例如成熟CEC),可最初由初步活體外研究及/或動物模型確定治療有效量。亦可由人類資料確定治療有效劑量。可基於所投與之化合物之相關生物可用性及效能來調節所施用之劑量。基於上文所描述之方法及其他熟知方法調節劑量以達成最大功效在一般熟習此項技術者之能力範圍內。
藥物動力學原理為修改給藥方案以在最小的不可接受的副作用下獲得所需程度之治療功效提供基礎。在藥劑之血漿濃度可量測且與治療窗相關之情況下,可獲得關於劑量修改的額外指導。
如本文中所使用,術語「治療(treat/treating/treatment)」包括消除、實質上抑制、減緩或逆轉病狀之發展,實質上改善病狀之臨床症狀,或實質上預防病狀(例如病理學病狀)之臨床症狀之出現,從而獲得有利或所需的臨床結果。治療亦指實現以下中之一或多者:(a)降低病症之嚴重程度;(b)限制所治療之病症之特徵性症狀的發展;(c)限制所治療之病症之特徵性症狀的惡化;(d)限制先前患有病症之患者的病症復發;及(e)限制先前無病症之症狀的患者之症狀復發。
有利或所需臨床結果,諸如藥理學及/或生理學作用包括(但不限於)預防可能易患疾病、病症或病狀但尚未經歷或呈現出疾病之症狀的個體發生疾病、病症或病狀(預防性治療);緩解疾病、病症或病狀之症狀;減輕疾病、病症或病狀之程度;使疾病、病症或病狀穩定(亦即,不惡化);防止疾病、病症或病狀擴散;延遲或減緩疾病、病症或病狀進程;改善或緩和疾病、病症或病狀;及其組合,以及與在不接受治療之情況下之預期存活期相比延長存活期。
如本文中所使用,疾病之「病徵」廣泛地指疾病之任何異常指示,其可在對患者進行檢查後發現;疾病之客觀指示而非症狀(其為疾病之主觀指示)。
如本文中所使用,疾病之「症狀」廣泛地指患者經歷及指示疾病之任何病理現象或在結構、功能或感覺上與正常情況之偏差。
I. 本發明之方法
本發明係基於發現用於促進CEC,例如成熟CEC之成熟且藉此實現產生成熟及功能性CEC之方法,其包括增加至少一種選自由以下組成之群之轉錄因子之表現:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。本發明之方法係可行且有效的,且引起例如由富潛能幹細胞產生可用於本文中所揭示之各種應用之CEC,例如成熟CEC,該等應用為例如治療影響CEC或適於藉由移植或投與CEC來治療之疾病或病症,包括例如原發性疾病,諸如法曲氏營養不良(Fuch's dystrophy)、虹膜角膜內皮症候群、後部多形性營養不良及先天性遺傳性內皮營養不良,可使用更換角膜內皮作為有效治療之繼發性疾病,包括角膜營養不良,或其中個體呈現引起大皰性角膜病變之角膜水腫之症狀、個體患有由使用隱形眼鏡或白內障手術引起之眼部損傷或其中個體考慮角膜移植之疾病。
在一些實施例中,增加PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。
在一些實施例中,增加FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。
在一些實施例中,增加TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。
在一些實施例中,增加LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。
在一些實施例中,增加POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。
在一些實施例中,角膜內皮祖細胞包含表現載體,其包含編碼至少一種轉錄因子之核酸。
在一些實施例中,增加角膜內皮祖細胞中之至少一種轉錄因子之表現包含誘導角膜內皮祖細胞中之至少一種轉錄因子之表現。
在一些實施例中,角膜內皮祖細胞係衍生自富潛能幹細胞,例如誘導性富潛能幹細胞或胚胎幹細胞。可使用任何用於使富潛能細胞分化成角膜內皮祖細胞之方法。舉例而言,可藉由分化如本文中所描述之富潛能幹細胞來獲得角膜內皮祖細胞。
在一些實施例中,富潛能幹細胞可經工程改造以包含表現載體,其包含編碼至少一種轉錄因子之核酸。在一些實施例中,表現載體包含以可操作方式連接至編碼至少一種轉錄因子之核酸之啟動子,例如內源性啟動子、人工啟動子或誘導型啟動子。
用於產生角膜內皮細胞之細胞
在本發明之某些實施例中,揭示用於藉由增加角膜內皮祖細胞中之至少一種選自由以下組成之群的轉錄因子之表現來產生CEC,例如成熟CEC之方法及組合物:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。在一些實施例中,CEC,例如成熟CEC及角膜內皮祖細胞係衍生自富潛能幹細胞,例如誘導性富潛能幹細胞、胚胎幹細胞、胎兒幹細胞及/或成人幹細胞。在其他實施例中,CEC,例如成熟CEC及角膜內皮祖細胞可衍生自體細胞。
A. 幹細胞
在正在發育的胚胎中,幹細胞可分化成所有特化的胚胎組織。在成年生物體中,幹細胞及祖細胞充當身體的修復系統,補充特化細胞,且亦維持再生器官(諸如血液、皮膚或腸道組織)之正常運轉。
富潛能幹細胞(諸如人類胚胎幹細胞(ESC)及誘導性富潛能幹細胞(iPSC))能夠在活體外長期增殖,同時保留分化成身體之所有細胞類型(包括角膜內皮祖細胞)之潛力。因此,此等細胞可潛在地為藥物開發及移植療法提供無限供應的患者特異性功能性CEC。富潛能幹細胞活體外分化成CEC,例如成熟CEC可涉及在不同分化階段添加不同生長因子且可能需要分化約10-30天(參見例如圖1)。與體細胞相比,富潛能幹細胞由於其無限的增殖能力而更宜作為用於CEC分化之起始細胞群體。
富潛能幹細胞,例如胚胎幹(ES)細胞或iPS細胞,可為所揭示之方法之起始材料。在本文中之任何實施例中,富潛能幹細胞可為人類富潛能幹細胞(hPSC)。可以此項技術中已知的任何方式培養富潛能幹細胞(PSC),諸如在存在或不存在飼養細胞之情況下。此外,使用任何方法產生之PSC皆可用作起始物質以產生CEC,例如成熟CEC。舉例而言,hES細胞可衍生自囊胚期胚胎,該等胚胎為卵子及精子之活體外授精的產物。或者,hES細胞可衍生自由早期卵裂期胚胎移出的一或多個分裂球,視情況不破壞胚胎之其餘部分。在其他實施例中,可使用核轉移產生hES細胞。在另一實施例中,可使用iPSC。作為起始材料,可使用先前冷凍保存的PSC。在另一實施例中,可使用從未進行冷凍保存之PSC。
在本發明之一個態樣中,在存在飼養細胞或不存在飼養細胞之條件下將PSC塗佈於細胞外基質上。在一個實施例中,可在細胞外基質上培養PSC,包括(但不限於)層黏連蛋白、纖維結合蛋白、玻璃連結蛋白、Matrigel、CellStart、膠原蛋白或明膠。在一些實施例中,細胞外基質為具有或不具有e-鈣黏素之層黏連蛋白。在一些實施例中,層黏連蛋白可選自包含以下之群:層黏連蛋白521、層黏連蛋白511或iMatrix511。在一些實施例中,飼養細胞為人類飼養細胞,諸如人類真皮成纖維細胞(HDF)。在其他實施例中,飼養細胞為小鼠胚胎成纖維細胞(MEF)。
在某些實施例中,在培養PSC時所使用之培養基可選自適合於培養PSC之任何培養基。在一些實施例中,可使用任何能夠支持PSC培養之培養基。舉例而言,熟習此項技術者可在市售或專屬培養基中選擇。
支持富潛能性之培養基可為此項技術中已知的任何此類培養基。在一些實施例中,支持富潛能性之培養基為Nutristem™。在一些實施例中,支持富潛能性之培養基為TeSR™。在一些實施例中,支持富潛能性之培養基為StemFit™。在其他實施例中,支持富潛能性之培養基為Knockout™ DMEM(Gibco),其可補充有Knockout™血清替代物(Gibco)、LIF、bFGF或任何其他因子。此等例示性培養基中之每一者為此項技術中已知的及市售的。在其他實施例中,支持富潛能性之培養基可補充有ROCK抑制劑、bFGF或任何其他因子。在一個實施例中,可以低濃度(例如4 ng/mL)補充bFGF。在另一實施例中,可以較高濃度(例如100 ng/mL)補充bFGF,此可引發PSC分化。
用於本發明之製造方法中之PSC之濃度不受特定限制。舉例而言,當使用10 cm培養皿時,使用每個培養皿1×10
4-1×10
8個細胞,較佳每個培養皿5×10
4-5×10
6個細胞,更佳每個培養皿1×10
5-1×10
7個細胞。
在一些實施例中,PSC係以約1,000-100,000個細胞/cm
2之細胞密度塗佈。在一些實施例中,PSC係以約5000-100,000個細胞/cm
2、約5000-50,000個細胞/cm
2或約5000-15,000個細胞/cm
2之細胞密度塗佈。在其他實施例中,以約10,000個細胞/cm
2之密度塗佈PSC。
在一些實施例中,用分化培養基更換支持富潛能性之培養基(例如,StemFit™或其他類似培養基)以使細胞分化成神經脊幹細胞或角膜內皮祖細胞。在一些實施例中,將培養基自支持富潛能性之培養基更換為分化培養基可在PSC之細胞培養期間的不同時間點進行,且亦可取決於PSC之初始塗佈密度。在一些實施例中,培養基之更換可在將PSC在富潛能性培養基中培養2-14天後進行。在一些實施例中,培養基之更換可在第2、3、4、5、6、7、8、9、10、11、12、13或14天進行。
在一些實施例中,適用於本文中所描述之方法之幹細胞包括(但不限於)胚胎幹細胞、誘導性富潛能幹細胞、間質幹細胞、骨髓衍生之幹細胞、造血幹細胞、軟骨細胞祖細胞、表皮幹細胞、胃腸道幹細胞、神經幹細胞、肝幹細胞、衍生之間質幹細胞、胰臟祖細胞、毛囊幹細胞、內皮祖細胞及平滑肌祖細胞。
在一些實施例中,用於本文中所描述之方法之幹細胞係自臍帶、胎盤、羊水、絨毛、囊胚、骨髓、脂肪組織、腦、周邊血液、胃腸道、臍帶血、血管、骨骼肌、皮膚、肝臟及月經血分離。
自各種來源分離人類幹細胞之詳細程序描述於Current Protocols in Stem Cell Biology (2007)中,其以全文引用的方式併入本文中。自各種來源分離及培養幹細胞之方法亦描述於美國專利案第5,486,359號、第6,991,897號、第7,015,037號、第7,422,736號、第7,410,798號、第7,410,773號、第7,399,632號中;其各自以全文引用的方式併入本文中。
B. 體細胞
在本發明之某些態樣中,亦提供轉分化方法,亦即,將一種體細胞類型直接轉化成另一種,例如自其他體細胞衍生CEC,例如成熟CEC。轉分化可涉及使用CEC分化轉錄因子基因或基因產物以增加體細胞中此類基因之表現量,以產生CEC,例如成熟CEC。
然而,人類體細胞之供應可能有限,尤其來自活供體之體細胞。為了向CEC分化提供無限供應的起始細胞,可藉由引入永生化基因或蛋白質,諸如hTERT及/或其他致癌基因使體細胞永生化。細胞之永生化可為可逆的(例如使用可移除的表現卡匣)或可誘導的(例如使用誘導型啟動子)。
在本發明之某些態樣中,體細胞可為初生細胞(非永生化細胞),諸如自動物新鮮分離之細胞,或可衍生自細胞株(永生化細胞)。細胞在自個體分離後可維持在細胞培養物中。在某些實施例中,細胞在用於本發明之方法中之前傳代一次或超過一次(例如,2-5、5-10、10-20、20-50、50-100次或更多次)。在一些實施例中,細胞在用於本發明之方法中之前已傳代不超過1、2、5、10、20或50次。
本文中所使用或描述之體細胞可為原生體細胞,或經工程改造之體細胞,亦即,已經基因改變之體細胞。本發明之體細胞通常為哺乳動物細胞,諸如人類細胞、靈長類動物細胞或小鼠細胞。其可藉由熟知方法獲得,且可自任何含有活的體細胞之器官或組織獲得,例如血液、骨髓、皮膚、肺、胰臟、肝臟、胃、腸道、心臟、生殖器官、膀胱、腎臟、尿道及其他泌尿器官等。
適用於本發明之哺乳動物體細胞包括(但不限於)塞特利氏細胞(Sertoli cells)、內皮細胞、粒層上皮細胞、神經元、胰島細胞、表皮細胞、上皮細胞、肝細胞、毛囊細胞、角質細胞、造血細胞、黑色素細胞、軟骨細胞、淋巴球(B及T淋巴球)、紅血球、巨噬細胞、單核球、單核細胞、心肌細胞及其他肌肉細胞等。
本文中所描述之方法可用於將一或多種體細胞,例如體細胞之群落或群體程式化為CEC,例如成熟CEC。在一些實施例中,本發明之細胞群體為實質上均勻的,因為至少90%之細胞顯示相關表現型或特徵。在一些實施例中,至少95%、96%、97%、98%、99%、99.5%、99.8%、99.9、99.95%或更多的細胞顯示相關表現型或特徵。在本發明之某些實施例中,體細胞具有分裂能力,亦即,體細胞不為有絲分裂後的。
體細胞可部分或完全分化。如本文中所描述,部分分化的體細胞及完全分化的體細胞皆可分化以產生角膜內皮細胞。
用於本發明之方法之轉錄因子
可藉由增加角膜內皮祖細胞中之至少一種本文中所描述之轉錄因子之表現來產生CEC,例如成熟CEC。可使用任何對促進CEC、成熟或功能重要的轉錄因子,例如選自表1中所描述之轉錄因子的至少一種轉錄因子。表1中所列舉之轉錄因子的所有同功型及變異體可包括在本發明中。本發明之轉錄因子之某些同功型或變異體之寄存編號的非限制性實例描述於表1中。
表
1.
用於產生成熟角膜內皮細胞之轉錄因子
轉錄因子 | 寄存編號 | mRNA SEQ ID NO. | 胺基酸SEQ ID NO. |
PITX2同功型1 | NM_153427 | 1 | 51 |
PITX2同功型2 | NM_001204397 | 2 | 52 |
PITX2同功型3 | NM_001204398 | 3 | 52 |
PITX2同功型4 | NM_001204399 | 4 | 51 |
PITX2同功型5 | NM_000325 | 5 | 53 |
PITX2同功型6 | NM_153426 | 6 | 52 |
FOXC1 | NM_001453 | 7 | 54 |
TFAP2B | NM_003221 | 8 | 55 |
LMX1B同功型1 | NM_001174146 | 9 | 56 |
LMX1B同功型2 | NM_002316 | 10 | 57 |
LMX1B同功型3 | NM_001174147 | 11 | 58 |
POU6F2同功型1 | NM_007252 | 12 | 59 |
POU6F2同功型2 | NM_001166018 | 13 | 60 |
ATF4 | NM_182810 | 14 | 61 |
ATMIN | NM_015251 | 15 | 62 |
BHLHE40 | NM_003670 | 16 | 63 |
CEBPD | NM_005195 | 17 | 64 |
CSRNP1 | NM_033027 | 18 | 65 |
DRAP1 | NM_006442 | 19 | 66 |
EGR1 | NM_001964 | 20 | 67 |
ELF2 | NM_201999 | 21 | 68 |
EMX2 | NM_004098 | 22 | 69 |
ESRRA | NM_004451 | 23 | 70 |
ETS 2 | NM_005239 | 24 | 71 |
FOS | NM_005252 | 25 | 72 |
FOSB | NM_006732 | 26 | 73 |
FOSL2 | NM_005253 | 27 | 74 |
GTF3A | NM_002097 | 28 | 75 |
HIF1A | NM_001530 | 29 | 76 |
JUN | NM_002228 | 30 | 77 |
JUNB | NM_002229 | 31 | 78 |
JUND | NM_001286968 | 32 | 79 |
KLF10 | NM_005655 | 33 | 80 |
KLF9 | NM_001206 | 34 | 81 |
MBD3 | NM_001281454 | 35 | 82 |
NFE2L1 | NM_003204 | 36 | 83 |
NME2 | NM_002512 | 37 | 84 |
NR1D1 | NM_021724 | 38 | 85 |
NR4A1 | NM_173157 | 39 | 86 |
PA2G4 | NM_006191 | 40 | 87 |
POU3F3 | NM_006236 | 41 | 88 |
RELA | NM_021975 | 42 | 89 |
TBX2 | NM_005994 | 43 | 90 |
TFAP2B | NM_003221 | 8 | 55 |
TFDP1 | NM_007111 | 44 | 91 |
TSC22D1 | NM_006022 | 45 | 92 |
USF2 | NM_003367 | 46 | 93 |
YBX1 | NM_004559 | 47 | 94 |
ZNF207 | NM_001098507 | 48 | 95 |
ZNF358 | NM_018083 | 49 | 96 |
ZNF395 | NM_018660 | 50 | 97 |
在一些實施例中,至少一種轉錄因子係選自由以下組成之群:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
在一些實施例中,可藉由增加角膜內皮祖細胞中之本文中所描述之轉錄因子之組合之表現來產生CEC,例如成熟CEC。舉例而言,在一些實施例中,可藉由增加角膜內皮祖細胞中之PITX2及至少一種(例如,1、2、3或4種)本文中所描述之其他轉錄因子之表現來產生CEC,例如成熟CEC。在一些實施例中,可藉由增加角膜內皮祖細胞中之FOXC1及至少一種(例如,1、2、3或4種)本文中所描述之其他轉錄因子之表現來產生CEC,例如成熟CEC。在一些實施例中,可藉由增加角膜內皮祖細胞中之TFAP2B及至少一種(例如,1、2、3或4種)本文中所描述之其他轉錄因子之表現來產生CEC,例如成熟CEC。在一些實施例中,可藉由增加角膜內皮祖細胞中之LMX1B及至少一種(例如,1、2、3或4種)本文中所描述之其他轉錄因子之表現來產生CEC,例如成熟CEC。在一些實施例中,可藉由增加角膜內皮祖細胞中之POU6F2及至少一種(例如,1、2、3或4種)本文中所描述之其他轉錄因子之表現來產生CEC,例如成熟CEC。
在一些實施例中,轉錄因子之組合係選自表1A中所描述之轉錄因子之組合:
表 1A. 轉錄因子之組合之實例
PITX2 + FOXC1 | PITX2 + FOXC1 + TFAP2B | PITX2 + FOXC1 + TFAP2B + LMX1B | PITX2 + FOXC1 + TFAP2B + LMX1B + POU6F2 |
PITX2 + TFAP2B | PITX2 + FOXC1 + LMX1B | PITX2 + FOXC1 + TFAP2B + POU6F2 | |
PITX2 + LMX1B | PITX2 + FOXC1 + POU6F2 | PITX2 + FOXC1 + LMX1B + POU6F2 | |
PITX2 + POU6F2 | PITX2 + TFAP2B + LMX1B | PITX2 + TFAP2B + LMX1B + POU6F2 | |
FOXC1 + TFAP2B | PITX2 + TFAP2B + POU6F2 | FOXC1 + TFAP2B + LMX1B + POU6F2 | |
FOXC1 + LMX1B | PITX2 + LMX1B + POU6F2 | ||
FOXC1 + POU6F2 | FOXC1 + TFAP2B + LMX1B | ||
TFAP2B + LMX1B | FOXC1 + TFAP2B + POU6F2 | ||
TFAP2B + POU6F2 | FOXC1 + LMX1B + POU6F2 | ||
LMX1B + POU6F2 | TFAP2B + LMX1B + POU6F2 |
在一些實施例中,轉錄因子為成對樣同源域轉錄因子2 (PITX2)。如本文中所使用,「PITX2」係指熟知的基因及蛋白質。術語PITX2包括蛋白質同功型及交替剪接或轉錄變異體。PITX2亦稱為垂體同源匣2、ARP1、Brx1、IDG2、IGDS、IGDS2、IHG2、IRID2、Otlx2、PTX2、RGS、RIEG、RIEG1、RS、成對樣同源域2及ASGD4。由PITX2基因編碼之蛋白質為調節原膠原離胺醯基羥化酶基因表現之轉錄因子且涉及眼睛、牙齒及腹部器官之發育。人類PITX2 mRNA轉錄物之序列可見於國家生物技術資訊中心(National Center for Biotechnology Information;NCBI) Ref Seq寄存編號NM_153427 (SEQ ID NO:1)中。PITX2同功型包括PITX2同功型2 (NM_001204397,SEQ ID NO:2)、PITX2同功型3 (NM_001204398,SEQ ID NO:3)、PITX2同功型4 (NM_001204399,SEQ ID NO:4)、PITX2同功型5 (NM_000325,SEQ ID NO:5)及PITX2同功型6 (NM_153426,SEQ ID NO:6)。
PITX2 mRNA序列之其他實例可容易地使用公開可用的資料庫獲得,例如GenBank、UniProt及OMIM。
PITX2之例示性序列包含SEQ ID NO:1、2、3、4、5或6中之任一者之核苷酸序列或由其編碼之胺基酸序列。在一些實施例中,PITX2包含與SEQ ID NO:1、2、3、4、5或6中之任一者之核苷酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之核苷酸序列。在一些實施例中,PITX2包含與由SEQ ID NO:1之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在一些實施例中,本發明之方法係關於使PITX2之表現相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少0.1倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少0.2倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少0.5倍。在一些實施例中,增加之Pitx2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少1倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少2倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少5倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少10倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少20倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少50倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少100倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少200倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少500倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少1,000倍。在一些實施例中,增加之PITX2之表現包含相對於角膜內皮祖細胞中之PITX2之內源性表現量增加至少10,000倍。
在一些實施例中,轉錄因子為叉頭框C1 (FOXC1)。如本文中所使用,「FOXC1」係指熟知的基因及蛋白質。術語FOXC1包括蛋白質同功型或交替剪接或轉錄變異體。FOXC1亦稱為ARA、FKHL7、FREAC-3、FREAC3、IGDA、IHG1、IRID1、RIEG3、叉頭框C1、ASGD3。由FOXC1基因編碼之蛋白質為在胚胎及眼睛發育之調節中起作用之轉錄因子。人類FOXC1 mRNA轉錄物之序列可見於國家生物技術資訊中心(NCBI) Ref Seq寄存編號NM_001453 (SEQ ID NO:7)中。FOXC1 mRNA序列之其他實例可容易地使用公開可用的資料庫獲得,例如GenBank、UniProt及OMIM。
FOXC1之例示性序列包含SEQ ID NO:7之核苷酸序列或由其編碼之胺基酸序列。在一些實施例中,FOXC1包含與SEQ ID NO:7之核苷酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之核苷酸序列。在一些實施例中,FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在一些實施例中,本發明之方法係關於使FOXC1之表現相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少0.1倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少0.2倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少0.5倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少1倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少2倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少5倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少10倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少20倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少50倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少100倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少200倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少500倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少1,000倍。在一些實施例中,增加之FOXC1之表現包含相對於角膜內皮祖細胞中之FOXC1之內源性表現量增加至少10,000倍。
在一些實施例中,轉錄因子為轉錄因子AP-2β (TFAP2B)。如本文中所使用,「TFAP2B」係指熟知的基因及蛋白質。TFAP2B亦稱為AP-2B、AP2-B、轉錄因子AP-2β、PDA2。術語TFAP2B包括交替剪接或轉錄變異體(例如,TFAP2B轉錄變異體X)及蛋白質同功型。由TFAP2B基因(AP2-β)編碼之蛋白質係認為在胚胎發育期間刺激細胞增殖及抑制特異性細胞類型之最終分化之轉錄因子。人類TFAP2B mRNA轉錄物之序列可見於國家生物技術資訊中心(NCBI) Ref Seq寄存編號NM_003221 (SEQ ID NO:8)中。TFAP2B mRNA序列之其他實例可容易地使用公開可用的資料庫獲得,例如GenBank、UniProt及OMIM。
TFAP2B之例示性序列包含SEQ ID NO:8之核苷酸序列或由其編碼之胺基酸序列。在一些實施例中,TFAP2B包含與SEQ ID NO:8之核苷酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之核苷酸序列。在一些實施例中,TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在一些實施例中,本發明之方法係關於使TFAP2B之表現相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少0.1倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少0.2倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少0.5倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少1倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少2倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少5倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少10倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少20倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少50倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少100倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少200倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少500倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少1,000倍。在一些實施例中,增加之TFAP2B之表現包含相對於角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少10,000倍。
在一些實施例中,轉錄因子為LIM同源匣轉錄因子1β (LMX1B)。如本文中所使用,「LMX1B」係指熟知的基因及蛋白質。術語LMX1B包括蛋白質同功型及交替剪接或轉錄變異體。LMX1B亦稱為LMX1.2、NPS1、LIM同源匣轉錄因子1β、FSGS10。由LMX1B基因編碼之蛋白質為在脊椎動物肢體之背腹側圖案化中起重要作用之轉錄因子。人類LMX1B mRNA轉錄物之序列可見於國家生物技術資訊中心(NCBI) Ref Seq寄存編號NM_001174146 (SEQ ID NO:9)中。LMX1B同功型包括LMX1B同功型2 (NM_002316,SEQ ID NO:10)及LMX1B同功型3 (NM_00117,SEQ ID NO:11)。LMX1B mRNA序列之其他實例可容易地使用公開可用的資料庫獲得,例如GenBank、UniProt及OMIM。
例示性LMX1B之序列包含SEQ ID NO:9-11中之任一者之核苷酸序列及由其編碼之胺基酸序列。在一些實施例中,LMX1B包含與SEQ ID NO:9-11中之任一者之核苷酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之核苷酸序列。在一些實施例中,LMX1B包含與由SEQ ID NO:9-11之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在一些實施例中,本發明之方法係關於使LMX1B之表現相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少0.1倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少0.2倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少0.5倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少1倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少2倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少5倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少10倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少20倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少50倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少100倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少200倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少500倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少1,000倍。在一些實施例中,增加之LMX1B之表現包含相對於角膜內皮祖細胞中之LMX1B之內源性表現量增加至少10,000倍。
在一些實施例中,轉錄因子為POU類別6同源匣2 (POU6F2)。如本文中所使用,「POU6F2」係指熟知的基因及蛋白質。術語POU6F2包括交替剪接或轉錄變異體及蛋白質同功型。由POU6F2基因編碼之蛋白質為涉及諸如細胞定型及分化之發育過程之轉錄因子。人類POU6F2 mRNA轉錄物之序列可見於國家生物技術資訊中心(NCBI) Ref Seq寄存編號NM_007252 (SEQ ID NO:12)中。POU6F2之其他同功型包括POU6F2同功型2 (NM_001166018,SEQ ID NO:13)。POU6F2 mRNA序列之其他實例可容易地使用公開可用的資料庫獲得,例如GenBank、UniProt及OMIM。
例示性POU6F2之序列包含SEQ ID NO:12-13中之任一者之核苷酸序列或由其編碼之胺基酸序列。在一些實施例中,POU6F2包含與SEQ ID NO:12-13中之任一者之核苷酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之核苷酸序列。在一些實施例中,POU6F2包含與由SEQ ID NO:12-13之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
在一些實施例中,本發明之方法係關於使POU6F2之表現相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少0.1倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少0.2倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少0.5倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少1倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少2倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少5倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少10倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少20倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少50倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少100倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少200倍。在一些實施例中,增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少500倍。增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少1,000倍。增加之POU6F2之表現包含相對於角膜內皮祖細胞中之POU6F2之內源性表現量增加至少10,000倍。
增加轉錄因子之表現
用於遞送編碼本發明之轉錄因子之核酸之載體可經構築以在本發明之細胞(例如,角膜內皮祖細胞、神經脊幹細胞或富潛能幹細胞,例如胚胎幹細胞或誘導性富潛能幹細胞)中表現轉錄因子。在一些實施例中,核酸為DNA。在一些實施例中,核酸為RNA。在一些實施例中,核酸為經修飾之DNA。在一些實施例中,核酸為經修飾之RNA。
此外,蛋白質轉導組合物或方法亦可用於在本發明之方法中實現轉錄因子之表現。
A. 核酸遞送系統
熟習此項技術者將熟知如何經由標準重組技術構築載體(參見例如Sambrook等人, 2001及Ausubel等人, 1996,其各自以全文引用之方式併入本文中)。包含編碼至少一種本發明之轉錄因子之核酸的載體包括(但不限於)病毒載體、非病毒載體及/或誘導型表現載體。
如本文中所使用,「核酸」係指脫氧核糖核苷酸、核糖核苷酸或經修飾之核苷酸,及其呈單股或雙股形式之聚合物。該術語涵蓋含有已知的核苷酸類似物或經修飾之主鏈殘基或鍵聯之核酸,其為合成、天然存在及非天然存在的,具有與參考核酸類似之結合特性且在某些情況下,以與參考核苷酸類似之方式代謝。此類類似物之實例包括(但不限於)硫代磷酸酯、胺基磷酸酯、甲基磷酸酯、對掌性膦酸甲酯、2-O-甲基核糖核苷酸、肽-核酸(PNA)。
如本文中所使用,「核苷酸」係如此項技術中公認地用於包括具有天然鹼基(標準)及此項技術中熟知的經修飾之鹼基之核苷酸。此類鹼基通常位於核苷酸糖部分之l'位置。核苷酸通常包含鹼基、糖及磷酸酯基。核苷酸可在糖、磷酸酯及/或鹼基部分處未經修飾或經修飾(亦可互換地稱為核苷酸類似物、經修飾之核苷酸、非天然核苷酸、非標準核苷酸等;參見例如Usman及McSwiggen, 見上文;Eckstein等人, 國際PCT公開案第WO 92/07065號;Usman等人, 國際PCT公開案第WO 93/15187號;Uhlman及Peyman, 見上文,其皆以引用之方式併入本文中)。此項技術中存在經修飾之核酸鹼基之若干實例,如由Limbach等人, Nucleic Acids Res. 22:2183, 1994概述。可引入核酸分子中之鹼基修飾之一些非限制性實例包括次黃嘌呤、嘌呤、吡啶-4-酮、吡啶-2-酮、苯基、假尿嘧啶、2,4,6-三甲氧基苯、3-甲基尿嘧啶、二氫尿苷、萘基、胺基苯基、5-烷基胞嘧啶核苷(例如,5-甲基胞嘧啶核苷)、5-烷基尿苷(例如,胸腺嘧啶核糖核苷)、5-鹵尿苷(例如,5-溴尿苷)或6-氮雜嘧啶或6-烷基嘧啶(例如,6-甲基尿苷)、丙炔等(Burgin等人, Biochemistry 35:14090, 1996;Uhlman及Peyman, 見上文)。在此態樣中,「經修飾之鹼基」意謂位於l'位置或其等效位置處的除腺嘌呤、鳥嘌呤、胞嘧啶及尿嘧啶以外之核苷酸鹼基。
載體亦可包含其他組分或功能,從而進一步調節基因遞送及/或基因表現,或以其他方式為目標細胞提供有益的特性。此類其他組分包括例如影響結合或靶向細胞之組分(包括介導細胞類型或組織特異性結合之組分);影響細胞吸收載體核酸之組分;影響吸收後多核苷酸在細胞內定位之組分(諸如介導核定位之藥劑);及影響多核苷酸表現之組分。
此類組分亦可包括標記物,諸如可偵測及/或選擇標記物,其可用於偵測或選擇已吸收且表現由載體遞送之核酸的細胞。此類組分可作為載體之天然特徵提供(諸如使用具有介導結合及吸收之組分或功能的某些病毒載體),或載體可經修飾以提供此類功能。大量此類載體為此項技術中已知的且通常為可用的。當載體維持在宿主細胞中時,載體可在有絲分裂期間作為自主結構由細胞穩定複製,併入宿主細胞之基因體內,或維持在宿主細胞的細胞核或細胞質中。
熟習此項技術者將熟知如何經由標準重組技術構築載體(參見例如,Maniatis等人, 1988及Ausubel等人, 1994,其各自以引用之方式併入本文中)。
1. 病毒載體
本發明之某些態樣中提供編碼至少一種本發明之轉錄因子的病毒載體。病毒載體為一種利用病毒序列將核酸及可能的蛋白質引入細胞中之表現構築體。可用於遞送本發明之某些態樣之核酸之病毒載體的非限制性實例描述如下。
在一些實施例中,病毒載體為非整合病毒載體。本發明之例示性非整合病毒載體係選自由以下組成之群:腺相關病毒(AAV)載體,例如AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9、AAV10、AAV3B、AAV-2i8、RhlO、Rh74等;腺病毒(Ad)載體,包括其複製勝任型、複製缺陷型及無腸形式,例如Ad7、Ad4、Ad2、Ad5等;猿猴病毒40 (SV-40)載體、牛乳頭狀瘤病毒載體、埃-巴二氏病毒載體(Epstein-Barr virus vector)、疱疹病毒載體、痘瘡病毒載體、哈維鼠類肉瘤病毒載體(Harvey murine sarcoma virus vector)、鼠類乳房腫瘤病毒載體或勞斯肉瘤病毒載體(Rous sarcoma virus vector)。
在一些實施例中,病毒載體為整合病毒載體,例如反轉錄病毒載體。反轉錄病毒由於能夠將其基因整合至宿主基因體中、轉移大量外來遺傳物質、感染廣泛範圍之物種及細胞類型及在特殊細胞株中封裝而有希望作為基因遞送載體。
在一些實施例中,整合病毒載體係衍生自反轉錄病毒載體(例如,莫洛尼鼠類白血病病毒載體(Moloney murine leukemia virus vector;MoMLV)、MSCV、SFFV、MPSV、SNV等)、慢病毒載體(例如,衍生自HIV-1、HIV-2、SIV、BIV、FIV等)或由其衍生之載體。
重組載體亦能夠感染非分裂細胞,且可在本發明之方法中用於活體內及離體基因轉移及核酸序列之表現。舉例而言,能夠感染非分裂細胞之重組慢病毒描述於美國專利案第5,994,136號中,其以全文引用之方式併入本文中,其中用兩種或更多種攜帶封裝功能之載體(亦即,gag、pol及env,以及rev及tat)轉染適合的宿主細胞(亦即,產生病毒之細胞,且不為本發明之角膜內皮祖細胞或CEC)。
2. 游離基因組載體及其他非病毒載體
在本發明之某些態樣中亦可提供基於質體或脂質體之染色體外(亦即,游離基因組)載體之使用。此類游離基因組載體可包括例如基於oriP之載體及/或編碼EBNA-1之衍生物之載體。此等載體可允許將DNA之大型片段引入細胞中且在染色體外維持、每個細胞週期複製一次、有效地分配至子細胞且實質上不引發免疫反應。
其他染色體外載體包括其他基於親淋巴性疱疹病毒之載體。例示性親淋巴性疱疹病毒包括(但不限於) EBV、卡波西氏肉瘤疱疹病毒(Kaposi's sarcoma herpes virus;KSHV);狨疱疹病毒(Herpes virus saimiri;HS)及馬立克氏病病毒(Marek's disease virus;MDV)。亦涵蓋其他來源之基於游離基因體之載體,諸如酵母ARS、腺病毒、SV40或BPV。
在一些實施例中,載體為非病毒載體。在一些實施例中,非病毒載體係選自由以下組成之群:質體DNA、線性雙股DNA (dsDNA)、線性單股DNA (ssDNA)、奈米質體、微型環DNA、單股寡脫氧核苷酸(ssODN)、DDNA寡核苷酸、單股mRNA (ssRNA)及雙股mRNA (dsRNA)。
在一些實施例中,非病毒載體包含裸核酸、脂質體、樹枝狀聚合物、奈米粒子、脂質-聚合物系統、固體脂質奈米粒子及/或脂質體魚精蛋白/DNA脂質複合物(LPD)。
在一些實施例中,非病毒載體包含mRNA。在一些實施例中,mRNA可以裸修飾mRNA形式傳遞,例如在蔗糖-檸檬酸鹽緩衝液或生理鹽水溶液中。在其他實施例中,非病毒載體包含與轉染試劑,諸如Lipofectamine 2000、jetPEI、RNAiMAX及/或Invivofectamine複合之mRNA。為了保護mRNA免受核酸酶降解且屏蔽其負電荷,含有胺之材料亦常用作非病毒載體。最成熟的mRNA遞送方法之一為共同調配至脂質奈米粒子(LNP)中。LNP調配物典型地由以下構成:(1)可離子化或陽離子脂質或聚合材料,其攜有三級胺或四級胺以囊封聚陰離子mRNA;(2)兩性離子脂質(例如,1,2-二油醯基-sn-甘油-3-磷酸乙醇胺[DOPE]),其與細胞膜中之脂質類似;(3)膽固醇,其使LNP之脂質雙層穩定;及(4)聚乙二醇(PEG)脂質,其為奈米粒子提供水合層、改良膠體穩定性且減少蛋白質吸收。包含mRNA之例示性非病毒載體描述於Kowalksi等人, 2019,
Mol Ther.; 27(4): 710-728中;其以全文引用的方式併入本文中。
3. 基於轉位子之系統
根據一個特定實施例,核酸之引入可使用轉位子-轉位酶系統。所使用之轉位子-轉位酶系統可為熟知的睡美人(Sleeping Beauty)、青蛙王子(Frog Prince)轉位子-轉位酶系統(關於後者之描述參見例如EP1507865)或TTAA特異性轉位子piggyBac系統。
轉位子為可在單個細胞之基因體內移動至不同位置之DNA序列,此過程稱為轉位。在該過程中,其可引起突變且改變基因體中之DNA之量。存在多種移動遺傳元件,且其可基於其轉位機制進行分組。I類移動遺傳元件或反轉錄轉位子藉由首先轉錄為RNA,隨後藉由反轉錄酶反轉錄成DNA,且隨後插入基因體中之另一位置來複製自身。II類移動遺傳元件使用轉位酶在基因體內「剪貼」而直接自一個位置移動至另一個位置。
4. 同源重組
同源重組(HR)為一種靶向基因體修飾技術,自1980年代中期以來一直為在哺乳動物細胞中進行基因體工程改造之標準方法。使用大範圍核酸酶或導向核酸內切酶,諸如I-SceI,已用於提高HR之效率。天然大範圍核酸酶以及經工程改造以具有改良之靶向特異性之大範圍核酸酶皆已用於提高HR效率。另一種提高HR效率之途徑為用可程式化DNA特異性域工程改造嵌合核酸內切酶。鋅指核酸酶(ZFN)為此類嵌合分子之一個實例,其中鋅指DNA結合域與IIS型限制性核酸內切酶,諸如FokI之催化域融合。另一種此類特異性分子包括與IIS型限制性核酸內切酶,諸如FokI之催化域融合之轉錄活化因子樣效應子(TALE) DNA結合域。另一種促進靶向基因體修飾之此類分子包括CRISPR/Cas系統,例如Ran等人, 2013;
Nature Protocols8:2281-2308中所述;其以全文引用的方式併入本文中。
B. 調節元件
載體中所包括之真核表現卡匣較佳含有(以5'至3'方向)以可操作方式連接至蛋白編碼序列之真核轉錄啟動子、包括介入序列之剪接信號及轉錄終止/聚腺苷酸化序列。
1. 啟動子 / 強化子
「啟動子」為控制序列,其為核酸序列中控制轉錄起始及速率之區域。其可含有調節蛋白質及分子可結合之基因元件,諸如RNA聚合酶及其他轉錄因子,以起始核酸序列之特異性轉錄。片語「可操作地定位」、「以可操作方式連接(operatively linked/operably linked)」、「在……控制下」及「在轉錄控制下」意謂啟動子相對於核酸序列處於正確的功能位置及/或定向,以控制該序列之轉錄起始及/或表現。
啟動子通常包含用於定位RNA合成之起始位點的序列。額外啟動子元件調節轉錄起始之頻率。通常,此等元件定位於起始位點上游之30-110 bp區中,但許多啟動子已證實亦含有位於起始位點下游之功能元件。為了「在啟動子之控制下」引入編碼序列,將轉錄閱讀框架之轉錄起始位點之5'端置於所選擇的啟動子之「下游」(亦即,3'端)。「上游」啟動子刺激DNA之轉錄且促進經編碼之RNA之表現。
啟動子元件之間的間距通常為靈活的,因此當元件相對彼此倒置或移動時保留啟動子功能。在tk啟動子中,啟動子元件之間的間距可在活性開始下降之前增加至間隔50 bp。視啟動子而定,個別元件似乎可協作地或獨立地起活化轉錄作用。啟動子可與或可不與「強化子」(其係指涉及核酸序列之轉錄活化的順式作用調節序列)結合使用。
除以合成方式產生啟動子及強化子之核酸序列以外,可結合本文中所揭示之組合物使用重組選殖及/或核酸擴增技術,包括PCR™產生序列(參見美國專利案第4,683,202號及第5,928,906號,其各自以全文引用之方式併入本文中)。此外,經考慮,亦可使用引導非核細胞器(諸如粒線體、葉綠體及其類似物)內之序列之轉錄及/或表現的控制序列。
所使用之啟動子可為組成性的、組織特異性的、誘導性的及/或適用於在適當條件下引導所引入之DNA區段的大量表現,諸如在重組蛋白質及/或肽的大規模產生方面有利。啟動子可為人工或內源性的。
在一些實施例中,啟動子為誘導型啟動子。術語「誘導型啟動子」為此項技術中已知的,且係指僅回應於刺激而具有活性的啟動子。誘導型啟動子回應於內源性或外源性刺激,例如化合物(化學誘導劑)之存在或回應於環境、激素、化學及/或發育信號而選擇性地表現核酸分子。誘導型啟動子包括例如由光、熱、應力(例如鹽應力或滲透應力)、植物激素、創傷或化學物質(諸如乙醇、脫落酸(ABA)、茉莉酸酯、水楊酸或安全劑)誘導或調節之啟動子。在一些實施例中,誘導型啟動子為EF1a啟動子。在一些實施例中,誘導型啟動子為PGK啟動子。
在一些實施例中,異源核酸由選自由以下組成之群之啟動子序列控制:巨細胞病毒(CMV)即刻早期啟動子、RSV LTR、MoMLV LTR、磷酸甘油酸激酶-1 (PGK)啟動子、猿猴病毒40 (SV40)啟動子、CK6啟動子、甲狀腺素運載蛋白啟動子(TTR)、TK啟動子、四環素反應性啟動子(TRE)、HBV啟動子、hAAT啟動子、LSP啟動子、嵌合肝特異性啟動子(LSP)、E2F啟動子、端粒酶(hTERT)啟動子;巨細胞病毒強化子/雞β-肌動蛋白/兔.β.-血球蛋白啟動子(CAG)啟動子、延長因子1-α啟動子(EF1-α)啟動子、人類.β.-葡糖苷酸酶啟動子、雞.β.-肌動蛋白(CBA)啟動子、反轉錄病毒勞斯肉瘤病毒(RSV) LTR啟動子、二氫葉酸還原酶啟動子及β-肌動蛋白啟動子。在一些實施例中,異源核酸以可操作方式連接至適用於在CNS之一或多種細胞中表現治療性多肽或治療性核酸之啟動子。
在另一實施例中,將使用轉錄因子之原生啟動子或其片段。當需要轉錄因子之表現模擬原生表現時可使用原生啟動子。當必須在時間上或發育上,或以組織特異性方式,或回應於特異性轉錄刺激調節轉錄因子之表現時,可使用原生啟動子。在另一實施例中,其他原生表現控制元件,諸如強化子元件、聚腺苷酸化位點或Kozak共有序列,亦可用於模擬原生表現。
誘導型啟動子允許基因表現之調節且可由以下調節:外源提供之化合物;環境因素,諸如溫度;或特定生理狀態(例如急性期,細胞之特定分化狀態)之存在,或僅在複製細胞中調節。誘導型啟動子及誘導型系統可自許多商業來源獲得,包括(但不限於)Invitrogen、Clontech及Ariad。已描述許多其他系統且其可由熟習此項技術者容易地選擇。由外源提供之啟動子調節之誘導型啟動子之實例包括鋅誘導型綿羊金屬硫蛋白(MT)啟動子、地塞米松(dexamethasone) (Dex)誘導型小鼠乳房腫瘤病毒(MMTV)啟動子、T7聚合酶啟動子系統(WO 98/10088);蛻皮激素昆蟲啟動子(No等人,P
roc. Natl. Acad. Sci. USA, 93:3346-3351 (1996))、四環素可抑制型系統(Gossen等人,
Proc. Natl. Acad. Sci. USA, 89:5547-5551 (1992))、四環素誘導型系統(Gossen等人,
Science, 268:1766-1769 (1995), 亦參見Harvey等人,
Curr. Opin. Chem. Biol., 2:512-518 (1998))、RU486誘導型系統(Wang等人,
Nat. Biotech., 15:239-243 (1997)及Wang等人,
Gene Ther., 4:432-441 (1997))及雷帕黴素(rapamycin)誘導型系統(Magari等人,
J. Clin. Invest., 100:2865-2872 (1997))。可適用於此上下文之其他類型之誘導型啟動子係由特定生理學狀態(例如溫度、急性期)、細胞之特定分化狀態調節或僅在複製細胞中調節的啟動子。
在一些實施例中,異源核酸由在CEC譜系之一或多種細胞中表現之啟動子序列控制。CEC特異性啟動子可包括用於任何以下基因之啟動子:ATP6V1G1 (遞送V1子單元G1之ATP酶H+,C4orf49 (MGARP) (定位富含麩胺酸之蛋白質之粒線體)、CA12 (碳酸酐酶12)、COL4A3 (IV型膠原蛋白α3鏈)、COL8A1 (VIII型膠原蛋白α1鏈)、COL8A2 (VIII型膠原蛋白α2蛋白質)、DNAC6 (DNAJ熱休克蛋白質家族(HSP40)成員C6)、ENO1 (烯醇酶1)、ENO1P1 (烯醇酶1假基因1)、ENST00000354541、ENST00000357401、ERG (ETS轉錄因子)、FGF10 (成纖維細胞生長因子10)、FGF7 (成纖維細胞生長因子7)、IGFBP2 (胰島素生長因子樣結合蛋白質2)、ITGBL1 (整合素子單元β樣1)、LMX1B (LIM同源匣轉錄因子1β)、MIR184 (微型RNA 184)、MSMP (微精漿蛋白,前列腺相關)、PITX2 (成對樣同源域2)、POU6F2 (POU類別6同源匣2)、PTGDS (前列腺素D2合成酶)、SHC4 (SHC轉接蛋白質4)、SLC4A11 (溶質載體家族4成員11)、SLC4A4 (溶質載體家族4成員4)以及TFAP2B (轉錄因子AP-2β)及ZFHX4 (鋅指同源匣4) (Yoshihara等人, 2017, EBio Medicine, 25(2017), 第175-186頁)。在一些實施例中,啟動子序列可廣泛地表現於生物體中,且因此可藉由將其遞送至細胞而表現於細胞中,例如富潛能幹細胞、神經脊幹細胞、角膜內皮祖細胞或CEC,例如成熟CEC。在其他實施例中,可使用特異性表現於CEC譜系之細胞(例如,神經脊幹細胞、角膜內皮祖細胞或CEC,例如成熟CEC)中之啟動子序列。
此外,任何啟動子/強化子組合(根據例如真核啟動子資料庫EPDB,經由萬維網epd.isb-sib.ch/)亦可用於驅動表現。啟動子之非限制性實例包括組成性EF1α啟動子;早期或晚期病毒啟動子,諸如SV40早期或晚期啟動子、巨細胞病毒(CMV)即刻早期啟動子、勞斯肉瘤病毒(RSV)早期啟動子;真核細胞啟動子,諸如β肌動蛋白啟動子、GADPH啟動子、金屬硫蛋白啟動子;及串聯反應元件啟動子,諸如環狀AMP反應元件啟動子(cre)、血清反應元件啟動子(sre)、佛波醇酯啟動子(TPA)及靠近最小TATA盒之反應元件啟動子(tre)。
2. 起始信號及內部核糖體結合位點
特定起始信號亦可用於編碼序列之有效轉譯。此等信號包括ATG起始密碼子或相鄰序列。可能需要提供包括ATG起始密碼子之外源性轉譯控制信號。一般熟習此項技術者將容易地能夠確定此情形且提供必需信號。眾所周知,起始密碼子必須與所需編碼序列之閱讀框架「同框」,以確保整個插入物之轉譯。外源性轉譯控制信號及起始密碼子可為天然或合成的。表現效率可藉由包括適當轉錄強化子元件來提高。
在本發明之某些實施例中,使用內部核糖體入口位點(IRES)元件以用於產生多基因或多順反子訊息。IRES元件能夠繞過5'甲基化帽依賴性轉譯之核糖體掃描模型且在內部位點開始轉譯。IRES元件可連接至異源開放閱讀框架。多個開放閱讀框架可共同轉錄,各自藉由IRES分離,產生多順反子訊息。藉助於IRES元件,各開放閱讀框架可接近核糖體以便有效轉譯。使用單一啟動子/強化子轉錄單一訊息可有效表現多個基因(參見美國專利案第5,925,565號及第5,935,819號;其各自以全文引用的方式併入本文中)。
在一些實施例中,自我裂解序列可用於共同表現基因。如本文中所使用,術語「自我裂解序列」係指連接開放閱讀框架以形成單一順反子且在轉譯期間誘導核糖體跳躍之序列。核糖體跳躍引起由自我裂解序列連接之兩個編碼序列轉譯成兩個獨立的肽。舉例而言,2A自我裂解序列可用於在本發明中所提供之構築體中產生基因之連鎖表現或共同表現。例示性自我裂解序列包括(但不限於)T2A、P2A、E2A及F2A,如表2中所描述。
表 2. 例示性 2A 序列
T2A | GSGEGRGSLLTCGDVEENPGP | SEQ ID NO:182 |
P2A | GSGATNFSLLKQAGDVEENPGP | SEQ ID NO:183 |
E2A | GSGQCTNYALLKLAGDVESNPGP | SEQ ID NO:184 |
F2A | GSGVKQTLNFDLLKLAGDVESNPGP | SEQ ID NO:185 |
在一些實施例中,T2A包含與SEQ ID NO:182之胺基酸序列具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%一致性之胺基酸序列或編碼此類胺基酸序列之核酸。
在一些實施例中,P2A包含與SEQ ID NO:183之胺基酸序列具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%一致性之胺基酸序列或編碼此類胺基酸序列之核酸。
在一些實施例中,E2A包含與SEQ ID NO:184之胺基酸序列具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%一致性之胺基酸序列或編碼此類胺基酸序列之核酸。
在一些實施例中,F2A包含與SEQ ID NO:185之胺基酸序列具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%一致性之胺基酸序列或編碼此類胺基酸序列之核酸。
3. 複製起點
為了在宿主細胞中繁殖載體,其可含有一或多個複製起點位點(通常稱為「ori」),例如對應於如上文所描述之EBV之oriP或經基因工程改造以在程式化中具有類似或升高之功能之oriP的核酸序列,其為啟動複製之特定核酸序列。或者,可使用如上文所描述之其他超染色體複製病毒或自主複製序列(ARS)之複製起點。
4. 選擇及可篩選標記物
在本發明之某些實施例中,含有本發明之核酸構築體的細胞可藉由在表現載體中包括標記物而在活體外或活體內鑑別。此類標記物將賦予細胞可鑑別之變化,允許容易地鑑別含有表現載體之細胞。通常,選擇標記物為賦予允許選擇之特性的標記物。陽性選擇標記物為標記物之存在允許其選擇的標記物,而陰性選擇標記物為其存在阻止其選擇的標記物。陽性選擇標記物之實例為耐藥性標記物。
通常,包括藥物選擇標記物有助於選殖及鑑別轉形體,例如賦予對新黴素、嘌呤黴素、潮黴素、DHFR、GPT、吉歐黴素(zeocin)及組織醇之抗性的基因為適用的選擇標記物。除了賦予允許基於條件之實施來鑑別轉形體之表現型的標記物以外,亦涵蓋其他類型之標記物,包括基於比色分析之可篩選標記物,諸如GFP。
或者,可使用可篩選酶作為陰性選擇標記物。在某些實施例中,陰性選擇標記物包含一或多種自殺基因,其在投與前藥後實現基因產物轉變為殺傷其宿主細胞的化合物。本發明之例示性自殺基因包括(但不限於)誘導型凋亡蛋白酶9 (或凋亡蛋白酶3或7)、CD20、CD52、EGFR、胸苷激酶、胞嘧啶脫胺酶、HER1及其任何組合。此項技術中已知的可用於本發明之其他自殺基因包括嘌呤核苷磷酸化酶(PNP)、細胞色素p450酶(CYP)、羧基肽酶(CP)、羧酸酯酶(CE)、硝基還原酶(NTR)、鳥嘌呤核糖基轉移酶(XGRTP)、糖苷酶及胸苷磷酸化酶(TP)。
熟習此項技術者亦將知曉如何使用免疫標記物,可能與FACS分析相結合。咸信所使用之標記物並不重要,只要其能夠與編碼基因產物之核酸同時表現即可。選擇及可篩選標記物之其他實例為熟習此項技術者所熟知的。本發明之一個特徵包括在轉錄因子在角膜內皮細胞中實現所需變化後,使用選擇及可篩選標記物選擇此等細胞。
在本發明之某些實施例中,含有本發明之核酸構築體的細胞可藉由在表現載體中包括標記物而在活體外或活體內鑑別。此類標記物將賦予細胞可鑑別之變化,允許容易地鑑別含有表現載體之細胞。通常,選擇標記物為賦予允許選擇之特性的標記物。陽性選擇標記物為標記物之存在允許其選擇的標記物,而陰性選擇標記物為其存在阻止其選擇的標記物。陽性選擇標記物之實例為耐藥性標記物。
通常,包括藥物選擇標記物有助於選殖及鑑別轉形體,例如賦予對新黴素、嘌呤黴素、潮黴素、DHFR、GPT、吉歐黴素及組織醇之抗性的基因為適用的選擇標記物。除了賦予允許基於條件之實施來鑑別轉形體之表現型的標記物以外,亦涵蓋其他類型之標記物,包括基於比色分析之可篩選標記物,諸如GFP。
C. 核酸遞送
在某些實施例中,增加角膜內皮祖細胞中之至少一種轉錄因子之表現包含使細胞,例如角膜內皮祖細胞或富潛能幹細胞與至少一種轉錄因子接觸。在一些實施例中,細胞,例如角膜內皮祖細胞或富潛能幹細胞包含表現載體,其包含編碼至少一種轉錄因子之核酸。
將核酸(諸如DNA、RNA、經修飾之DNA或經修飾之RNA)引入本發明之細胞(例如,角膜內皮祖細胞或富潛能幹細胞)中可使用任何適用於細胞之轉型之核酸遞送之方法,如本文中所描述或如一般熟習此項技術者已知。該等方法包括(但不限於)直接遞送DNA,諸如藉由離體轉染(Wilson等人, 1989, Nabel等人, 1989;其各自以全文引用之方式併入本文中)、藉由注射(美國專利案第5,994,624號、第5,981,274號、第5,945,100號、第5,780,448號、第5,736,524號、第5,702,932號、第5,656,610號、第5,589,466號及第5,580,859號;其各自以全文引用之方式併入本文中),包括顯微注射(Harland及Weintraub, 1985;美國專利案第5,789,215號;其各自以全文引用之方式併入本文中);藉由電穿孔(美國專利案第5,384,253號;Tur-Kaspa等人, 1986;Potter等人, 1984;其各自以全文引用之方式併入本文中);藉由磷酸鈣沈澱(Graham及Van Der Eb, 1973;Chen及Okayama, 1987;Rippe等人, 1990;其各自以全文引用之方式併入本文中);藉由使用DEAE-聚葡萄糖,接著使用聚乙二醇;藉由直接音波加載(Fechheimer等人, 1987;其以全文引用之方式併入本文中);藉由脂質體介導之轉染(Nicolau及Sene, 1982;Fraley等人, 1979;Nicolau等人, 1987;Wong等人, 1980;Kaneda等人, 1989;Kato等人, 1991;其各自以全文引用之方式併入本文中)及受體介導之轉染(Wu及Wu, 1987;Wu及Wu, 1988;其各自以全文引用之方式併入本文中);藉由微彈轟擊(PCT申請案第WO 94/09699號及第WO 95/06128號;美國專利案第5,610,042號、第5,322,783號、第5,563,055號、第5,550,318號、第5,538,877號及第5,538,880號;其各自以全文引用之方式併入本文中);藉由與碳化矽纖維一起攪拌(Kaeppler等人, 1990;美國專利案第5,302,523號及第5,464,765號;其各自以全文引用之方式併入本文中);藉由農桿菌介導之轉型(美國專利案第5,591,616號及第5,563,055號;其各自以全文引用之方式併入本文中);藉由乾化/抑制介導之DNA吸收(Potrykus等人, 1985;其以全文引用之方式併入本文中),及此類方法之任何組合。經由應用諸如此等方法之技術,可穩定或暫時地轉型細胞器、細胞、組織或生物體。
在本發明之某一實施例中,核酸可包埋於脂質複合物(諸如脂質體)中。脂質體為以磷脂雙層膜及內部水性介質為特徵之囊泡結構。多層脂質體具有由水性介質分隔之多個脂質層。其在磷脂懸浮於過量的水性溶液中時自發地形成。脂質組分在形成封閉結構之前進行自我重排,且在脂質雙層之間截留水及溶解的溶質。亦考慮與Lipofectamine(Gibco BRL)或Superfect(Qiagen)複合之核酸。脂質體之使用量可根據脂質體之性質以及所使用之細胞而變化,例如可考慮每1至1000萬個細胞使用約5至約20 μg載體DNA。
在本發明之某些實施例中,經由電穿孔將核酸引入細胞器、細胞、組織或生物體中。電穿孔涉及將細胞及DNA之懸浮液暴露於高壓放電。可使得受體細胞更易於藉由機械創傷轉形。此外,載體之使用量可根據所使用之細胞之性質而變化,例如,可考慮每1至1000萬個細胞使用約5至約20 μg載體DNA。
在本發明之其他實施例中,使用磷酸鈣沈澱將核酸引入細胞中。
在另一實施例中,使用DEAE-聚葡萄糖,接著使用聚乙二醇將核酸遞送至細胞中。
本發明之其他實施例包括藉由直接音波加載來引入核酸。
微彈轟擊技術亦可用於將核酸引入至少一個細胞器、細胞、組織或生物體中(美國專利案第5,550,318號;第5,538,880號;第5,610,042號;及PCT申請案WO 94/09699;其各自以引用的方式併入本文中)。此方法取決於將DNA包覆之微彈加速至高速度,使其能夠刺穿細胞膜且進入細胞而不將其殺傷的能力(Klein等人, 1987;其以全文引用的方式併入本文中)。此項技術中已知多種適用於本發明之方法之微彈轟擊技術。
D. 基因開關
在一些實施例中,本發明之細胞(例如,富潛能幹細胞或角膜內皮祖細胞)經工程改造以包含編碼本發明之轉錄因子之基因開關構築體。基因開關構築體提供用於構築複雜的基因迴路之基本構築嵌段,該等基因迴路將細胞轉形為適用的基於細胞之機器,以用於生物醫學應用。配位體反應性基因開關構築體為細胞感測器,其能夠處理特定信號以產生基因產物反應。其參與複雜的基因迴路,產生複雜的電路拓樸結構,使人聯想到電子裝置且能夠為經工程改造之細胞提供記憶事件、振盪蛋白質生產及執行複雜的資訊處理任務(參見Ausländer等人, 2016;
Cold Spring Harb Perspect Biol.; 8(7): a023895;其以全文引用的方式併入本文中)。基於基因開關構築體設計策略,本發明之細胞(例如,富潛能幹細胞或角膜內皮祖細胞)可經工程改造以包含編碼本發明之轉錄因子之基因開關構築體以及各種合成系統,由此感測不同的配位體輸入,其又介導編碼本發明之轉錄因子之基因開關構築體之表現。
1. 轉錄基因開關
在一些實施例中,基因開關構築體為轉錄基因開關構築體。在一些實施例中,轉錄基因開關構築體包含使用與轉錄調節因子蛋白融合之原核或真核調節因子蛋白,其與DNA操縱子序列結合,以配體反應性方式控制基因開關構築體之表現。在一些實施例中,轉錄基因開關構築體包含使用將原核調節因子蛋白與配位體或光誘發性二聚化系統(DS)組合,從而能夠實現轉錄調節因子蛋白之信號依賴性募集。在一些實施例中,轉錄基因開關構築體包含使用位於細胞表面之G蛋白偶聯受體(GPCR),該等受體感測胞外信號且經由信號傳導途徑觸發信號轉導以控制基因開關構築體之表現。在一些實施例中,轉錄基因開關構築體包含使用經工程改造之二鳥苷酸環化酶(DGCL),其以紅光反應性方式合成第二信使環狀二-GMP,觸發下游信號傳導途徑且引起基因開關構築體之轉錄活化。在一些實施例中,轉錄基因開關構築體包含使用Ausländer等人, 2016中所描述之任何合成系統;其以全文引用的方式併入本文中。
2. 轉錄後基因開關
在一些實施例中,基因開關構築體為轉錄後基因開關構築體。在一些實施例中,轉錄後基因開關構築體包含使用與初級微型RNA (pri-miRNA)分子融合之適體酶,從而能夠實現對pri-miRNA處理之配位體反應性控制及轉錄後目標基因控制。在一些實施例中,轉錄後基因開關構築體包含使用整合至信使RNA (mRNA)中之蛋白質反應性適體酶來調節其穩定性,此取決於存在或不存在蛋白配位體。在一些實施例中,轉錄後基因開關構築體包含使用與蛋白質結合適體結合之蛋白質,該等適體整合至小型髮夾RNA (shRNA)中且抑制shRNA處理,且允許蛋白質控制之基因開關構築體之表現。在一些實施例中,轉錄後基因開關構築體包含使用整合至mRNA之5'非轉譯區(UTR)中之蛋白質結合適體,以蛋白質依賴性方式控制轉譯起始。在一些實施例中,轉錄後基因開關構築體包含將蛋白質結合適體整合至剪接位點附近,以允許蛋白質反應性替代性剪接調節。在一些實施例中,轉錄後基因開關構築體包含使用ATetR結合適體與茶鹼反應性適體之組合,從而能夠實現TetR結合適體之茶鹼依賴性摺疊。當與同源適體結合時,TetR蛋白失去其DNA操縱子結合能力且在轉錄層面上影響基因表現。
整合酶亦可充當功能性基因開關控制器,活化編碼序列或經設計以在真核細胞中啟動的啟動子開關。整合酶在其位點識別及重組過程中展示準確性,且不具有細胞毒性。在一些實施例中,基因開關構築體包含使用由絲胺酸整合酶控制之基因開關,如Gomide等人, 2020,
Commun Biol.;3(1):255中所描述;其以全文引用的方式併入本文中。
E. 蛋白質轉導
在某些實施例中,可以足以產生成熟角膜內皮細胞之量使本發明之細胞(例如,角膜內皮祖細胞)與包含多肽之轉錄因子接觸。蛋白質轉導已用作增強大分子遞送至細胞中之方法。蛋白質轉導域可用於將轉錄因子多肽或其功能片段直接引入細胞中。
「蛋白質轉導域」或「PTD」為可穿過生物膜,尤其細胞膜之胺基酸序列。當連接至異源多肽時,PTD可增強異源多肽跨越生物膜之易位。PTD典型地共價連接(例如,藉由肽鍵)至異源DNA結合域。舉例而言,PTD及異源DNA結合域可由單一核酸編碼,例如在共同開放閱讀框架中或在共同基因之一或多個外顯子中。例示性PTD可包括10-30個胺基酸且可形成兩性螺旋。許多PTD之特徵為鹼性。舉例而言,鹼性PTD可包括至少4、5、6或8個鹼性殘基(例如,精胺酸或離胺酸)。PTD可能夠增強多肽易位至缺乏細胞壁之細胞或特定物種之細胞,例如哺乳動物細胞,諸如人類、猿猴、鼠類、牛類、馬類、貓類或綿羊細胞中。
PTD可連接至人工轉錄因子,例如使用可撓性連接子。可撓性連接子可包括一或多個甘胺酸殘基以允許自由旋轉。舉例而言,PTD可與轉錄因子之DNA結合域間隔至少10、20或50個胺基酸。PTD可相對於DNA結合域位於N端或C端。位於特定域之N端或C端並不需要與該特定域相鄰。舉例而言,位於DNA結合域之N端之PTD可藉由間隔子及/或其他類型之域與DNA結合域分開。PTD可以化學方式合成,隨後在存在或不存在連接子肽之情況下以化學方式與單獨製備的DNA結合域結合。人工轉錄因子亦可包括複數個PTD,例如複數個不同PTD或一個PTD之至少兩個複本。
若干蛋白質及小型肽具有獨立於經典受體或胞吞作用介導之途徑轉導或穿過生物膜的能力。此等蛋白質之實例包括HIV-1 TAT蛋白、單純疱疹病毒1(HSV-1)DNA結合蛋白VP22及果蠅觸角足(Drosophila Antennapedia;Antp)同源轉錄因子。此等蛋白質之小型蛋白質轉導域(PTD)可與其他大分子、肽或蛋白質融合,以成功地將其轉運至細胞中。此等蛋白質之轉導域的序列比對展示高鹼性胺基酸含量(Lys及Arg),其可有助於此等區域與膜中帶負電荷之脂質的相互作用。二級結構分析證實所有三個域之間不存在一致的結構。
使用此等轉導域之融合物的優點為蛋白質進入速度快、依賴於濃度且似乎對困難的細胞類型有效。PTD進一步描述於U.S. 2003/0082561;U.S. 2002/0102265;U.S. 2003/0040038中;其各自以全文引用的方式併入本文中。
除PTD以外,亦可使用細胞吸收信號。此類信號包括由細胞受體或其他表面蛋白特異性識別之胺基酸序列。細胞吸收信號與細胞之間的相互作用引起包括細胞吸收信號之人工轉錄因子的內化。一些PTD亦可藉由與細胞受體或其他表面蛋白之相互作用而發揮作用。
細胞培養
通常,在培養基中培養本發明之細胞,培養基為能夠維持細胞生長之富含營養物的緩衝溶液。
可藉由在培養基中,在使本文中所描述之轉錄因子之細胞內含量增加達到足以促進產生CEC,例如成熟CEC的條件下培養富潛能幹細胞或其他細胞(例如,角膜內皮祖細胞或神經脊幹細胞),來製備本發明之CEC。培養基亦可含有一或多種CEC分化劑,如各種生長因子。此等藥劑可幫助誘導細胞進入更成熟的表現型,或優先促進成熟細胞之存活,或具有此等作用之組合。
本發明中說明之CEC分化劑可包括能夠促進CEC譜系之細胞生長的可溶性生長因子(肽激素、細胞介素、配位體-受體複合物、及其他化合物,諸如硫酸軟骨素A、垂體提取物及抗壞血酸)。此類製劑之非限制性實例包括(但不限於)諾金(Noggin)、SB431542、鹼性成纖維細胞生長因子(FGF)、表皮生長因子(EGF)、Rock抑制劑、及神經生長因子(NGF)。其他因子可包括白血病抑制因子(LIF)、GSK3抑制劑、視黃酸、γ分泌酶抑制劑、TGFβ/活化素(Activin)/Nodal之BMP抑制劑(包括多索嗎啡(dorsomorphin)、脊索發生素(chordin)及卵泡抑素(follistatin))、IL-1、胰島素、TGF-α、TGF-β、肝素、胰島素樣生長因子I及II (IGF-I、IGF-2)、血小板衍生之生長因子B (PDGFB)及PDGFB促效劑、DKK2及DKK2促效劑、血管生成素樣蛋白質7 (ANGPL7)、B27補充劑及升糖素。
富潛能細胞或其他細胞(例如,角膜內皮祖細胞或神經脊幹細胞)可在諾金(例如人類諾金多肽,諸如NP_005441.1或其中所含之成熟多肽)及/或SB431542或衍生物(統稱為「雙重SMAD抑制劑」)之存在下分化。富潛能細胞或其他細胞(例如,角膜祖細胞或神經脊細胞)可在天然分泌之BMP抑制劑脊索發生素及卵泡抑素以及其類似物或模擬物、會與BMP2、BMP4及/或BMP7螯合之顯性負向受體或阻斷抗體、及/或多索嗎啡(或化合物C)之存在下分化。SMAD蛋白質之抑制亦可使用可溶性抑制劑執行,諸如SIS3 (6,7-二甲氧基-2-((2E)-3-(1-甲基-2-苯基-1H-吡咯并[2,3-b]吡啶-3-基-丙-2-烯醯基))-1,2,3,4-四氫異喹啉;Smad3之特異性抑制劑SIS3;抑制劑SMAD (例如SMAD6、SMAD7、SMAD10)中之一或多者或受體SMAD中之一者(SMAD1、SMAD2、SMAD3、SMAD5、SMAD8/9)之RNAi之過度表現。其他用於富潛能細胞或其他細胞(例如,角膜祖細胞或神經脊幹細胞)之分化之試劑可為白血病抑制因子(LIF)、GSK3抑制劑(CHIR 99021)、化合物E (γ分泌酶抑制劑XXI)及/或TGFβ抑制劑SB431542 (Li等人, Proc Natl Acad Sci USA. 2011年5月17日; 108(20):8299-304)。
經歷角膜祖細胞或神經脊誘導之富潛能幹細胞可在SB431542之存在下培養,培養基中之SB431542濃度可以低達10 nM、20 nM、50 nM、0.1 μM或更低,或高達20 μM、50 μM、100 μM或更高(諸如10 nM至100 μM、0.1 μM至50 μM、0.1-20 μM或1-20 μM,或約10 μM)。
富潛能細胞,諸如經歷角膜祖細胞或神經脊誘導之富潛能細胞可在存在諾金之情況下培養,諾金可以低至10 ng/ml、20 ng/ml、50 ng/ml、100 ng/ml或更低或高達700 ng/ml、1000 ng/ml、1500 ng/ml、2000 ng/ml、3000 ng/ml、4000 ng/ml、5000 ng/ml或更高(諸如10 ng/ml至5,000 ng/ml、100 ng/ml至700 ng/ml,或400 ng/ml至600 ng/ml,較佳約500 ng/ml)之濃度存在於培養基中。富潛能細胞亦可與SB431542及諾金之組合(例如,前述濃度之組合)一起培養。
鹼性FGF可存在於富潛能細胞之培養物中,例如在角膜祖細胞或神經脊誘導期間,其可以低至1 ng/ml、2 ng/ml、3 ng/ml、4 ng/ml、5 ng/ml、6 ng/ml或更低,或高達10 ng/ml、20 ng/ml、50 ng/ml、100 ng/ml、500 ng/ml或1 μg/ml (諸如1 ng/ml-1 μg/ml、1 ng/ml-100 ng/ml、2 ng/ml-10 ng/ml、6 ng/ml-100 ng/ml,或約6 ng/ml)之濃度存在於培養基中。
鹼性FGF可存在於角膜祖細胞、神經脊幹細胞或CEC之培養物(例如在自角膜祖細胞或神經脊幹細胞之CEC分化期間)或包含CEC之培養物中,其可以低至0.1 ng/ml、0.2 ng/ml、0.5 ng/ml、1 ng/ml、2 ng/ml、3 ng/ml、4 ng/ml、5 ng/ml、6 ng/ml或更低,或高達10 ng/ml、20 ng/ml、50 ng/ml、100 ng/ml、500 ng/ml或1 μg/ml (諸如0.1 ng/ml-1 μg/ml、0.1 ng/ml-400 ng/ml、0.1 ng/ml-100 ng/ml、0.1 ng/ml-10 ng/ml、1 ng/ml-100 ng/ml,或約6 ng/ml)之濃度存在於培養基中。
EGF可存在於角膜祖細胞、神經脊幹細胞或CEC之培養物(例如在自角膜祖細胞或神經脊幹細胞之CEC分化期間)或包含CEC之培養物中,其可以低至0.1 ng/ml、0.2 ng/ml、0.5 ng/ml、1 ng/ml、2 ng/ml、3 ng/ml、4 ng/ml、5 ng/ml、6 ng/ml或更低,或高達10 ng/ml、20 ng/ml、50 ng/ml、100 ng/ml、500 ng/ml或1 μg/ml (諸如0.1 ng/ml-1 μg/ml、0.1 ng/ml-400 ng/ml、0.1 ng/ml-100 ng/ml、0.1 ng/ml-10 ng/ml、1 ng/ml-100 ng/ml,或約5 μg/ml)之濃度存在於培養基中。
NGF可存在於角膜祖細胞、神經脊幹細胞或CEC之培養物(例如在自角膜祖細胞或神經脊幹細胞之CEC分化期間)或包含CEC之培養物中,其可以低至0.1 ng/ml、0.2 ng/ml、0.5 ng/ml、1 ng/ml、2 ng/ml、3 ng/ml、4 ng/ml、5 ng/ml、6 ng/ml或更低,或高達10 ng/ml、20 ng/ml、50 ng/ml、100 ng/ml、500 ng/ml或1 μg/ml (諸如0.1 ng/ml-1 μg/ml、0.1 ng/ml-400 ng/ml、0.1 ng/ml-100 ng/ml、0.1 ng/ml-10 ng/ml、1 ng/ml-100 ng/ml,或約20 ng/ml)之濃度存在於培養基中。
ROCK抑制劑可存在於富潛能幹細胞之培養物中,或在CEC分化期間存在。「ROCK抑制劑」係指抑制或減少細胞中之Rho相關激酶或其信號傳導途徑之功能的任何物質,諸如小分子、siRNA、miRNA、反義RNA或其類似物。如本文中所使用,「ROCK信號傳導途徑」可包括涉及細胞中之ROCK相關信號傳導途徑,諸如Rho-ROCK-肌凝蛋白II信號傳導途徑、其上游信號傳導途徑或其下游信號傳導途徑之任何信號處理器。可使用之例示性ROCK抑制劑為Stemgent中Stemolecule Y-27632、rho相關蛋白質激酶(ROCK)抑制劑(參見Watanabe等人, Nat Biotechnol. 2007年6月; 25(6):681-6)。其他ROCK抑制劑包括例如H-1152、Y-30141、Wf-536、HA-1077、羥基-HA-1077、GSK269962A及SB-772077-B。Doe等人, J. Pharmacol. Exp. Ther., 32:89-98, 2007;Ishizaki等人, Mol. Pharmacol., 57:976-983, 2000;Nakajima等人, Cancer Chemother. Pharmacol., 52:319-324, 2003;及Sasaki等人, Pharmacol. Ther., 93:225-232, 2002,其各自以引用之方式併入本文中如同以其全文所闡述一般。ROCK抑制劑可以如此項技術中已知的濃度及/或培養條件使用,例如美國公開案第2012/0276063號中所描述,其以全文引用之方式併入本文中。Rho相關激酶抑制劑之其他實例包括以下參考文獻中所揭示之化合物:美國專利案第4,678,783號、美國專利案第3,421,217號、WO99/20620、WO99/61403、WO02076976、WO02/076977、WO02/100833、WO03/059913、WO03/062227、WO2004/009555、WO2004/022541、WO2004/108724、WO2005/003101、WO2005/039564、WO2005/034866、WO2005/037197、WO2005/037198、WO2005/035501、WO2005/035503、WO2005/035506、WO2005/080394、WO2005/103050、WO2006/057270、WO2007/026664等。此類化合物可根據各別參考文獻中之每一者中所描述之方法製備。特定實例包括1-(5-異喹啉磺醯基)高哌𠯤(法舒地爾(fasudil))、(+)-反-4-(1-胺基乙基)-1-(4-吡啶基胺甲醯基)環己烷(Y-27632)及其類似物,以及其鹽,較佳醫藥學上可接受之鹽,諸如鹽酸鹽。在例示性實施例中,ROCK抑制劑之濃度可為約0.05至約50 μM,例如至少或約0.05、0.1、0.2、0.5、0.8、1、1.5、2、2.5、5、7.5、10、15、20、25、30、35、40、45或50 μM,包括任何可自其中衍生之範圍,或任何可有效促進細胞生長或存活之濃度。
角膜內皮祖細胞或神經脊幹細胞可在存在PDGFB (例如,人類PDGFB多肽,諸如NP_002599.1或其中所含之成熟多肽)之情況下培養,且培養基包含PDGFB,及/或PDGFAA或PDGFAB,佛波醇(Phorbol) 12-豆蔻酸酯13-乙酸酯(PMA)或血管內皮生長因子(VEGF)。包含角膜內皮祖細胞或神經脊幹細胞之培養物(諸如在包含富潛能細胞(在開始神經脊誘導之後或在神經脊誘導期間)或角膜內皮祖細胞之培養物中)可在存在PDGFB之情況下培養,PDGFB可以低至0.1 ng/ml、0.2 ng/ml、0.5 ng/ml、1 ng/ml或更低,或高達10 ng/ml、20 ng/ml、30 ng/ml、50 ng/ml、75 ng/ml、100 ng/ml、125 ng/ml、150 ng/ml、200 ng/ml、250 ng/ml或更高(諸如0.1 ng/ml至250 ng/ml、0.5 ng/ml至150 ng/ml、1-50 ng/ml、2-20 ng/ml,或較佳約10 ng/ml)之濃度存在於培養基中。
富潛能細胞或其他細胞(例如,角膜祖細胞或神經脊細胞)可在存在DKK2 (例如,人類DKK2多肽,諸如NP_055236.1或其中所含之成熟多肽)之情況下培養,且培養基包含DKK2。在預期產生神經脊幹細胞(例如,在存在雙重SMAD抑制劑之情況下培養)或角膜內皮祖細胞之條件下培養的神經脊幹細胞(無論自分化富潛能細胞或其他來源獲得)及/或分化富潛能細胞可在存在DKK2或DKK2促效劑之情況下培養。DKK2促效劑可包括任何可在功能上替代CEC之分化中之DKK2的Wnt途徑活化劑及/或抑制劑。除DKK2以外或替代DKK2,可使用靶向及減弱LRP5/6或Kremen之表現之RNAi。除DKK2以外或替代DKK2,亦可使用Wnt途徑抑制劑(諸如DKK 1、3、4以及Soggy)、分泌型捲曲相關蛋白(Frzb)以及Wnt抑制劑因子(WIF)或酪蛋白激酶1-7或其他使β-連環蛋白穩定或去穩定之因子。此外,除DKK2以外或替代DKK2,可使用調節LEF/TCF轉錄因子成員。例示性Wnt途徑活化劑包括Wnt蛋白質、編碼Wnt蛋白質之核酸、LiCl、Wnt途徑之負調節子之抑制劑(例如,RNAi或其他靶向軸蛋白及/或APC之抑制劑)、norrin、R-脊椎蛋白2。小分子Wnt途徑活化劑包括:(雜)芳基嘧啶、IQ1、BIO (6-溴靛玉紅-3'-肟)、2-胺基-4-[3,4-(亞甲二氧基)苯甲基-胺基]-6-(3-甲氧苯基)嘧啶-e、WAY-316606、QS11、SB-216763、SB-216763及DCA。小分子Wnt途徑抑制劑包括:IWR、吡維氯銨(pyrvinium)、ICG-001、PKF115-584 (及若干其他化合物)、IWP、Ant1.4Br/Ant 1.4Cl、氯硝柳胺(Niclosamide)、阿匹拉倫(apicularen)及巴弗洛黴素(bafilomycin)、XAV939、NSC668036、2,4-二胺基-喹唑啉及槲皮素(Quercetin)。可使用之其他例示性WNT途徑抑制劑包括ID8 (Hasagawa等人, Stem Cells Transl Med. 2012年1月; 1(1):18-28)、Wnt C59 (Proffitt Cancer Res,2012年11月27日首次線上公開, 2012; DOI:10.1158/0008-5472.CAN-12-2258)、CGK062 (Gwak等人, PLoS ONE. 2012; 7(10):e46697)、IWP2 (Blauwkamp等人, Nat Commun. 2012; 3:1070)、FH535 (Iida等人, PLoS One. 2012; 7(9):e44418)及利魯唑(Riluzole) (Zhao等人, J Biomol Screen. 2012年10月; 17(9):1252-63)。除DKK2以外或替代DKK2,亦可使用前述因子之組合,例如包含超過一種Wnt途徑活化劑、超過一種Wnt途徑抑制劑或至少一種Wnt途徑活化劑及至少一種Wnt途徑抑制劑之組合。
在開始神經脊誘導之後或在神經脊誘導期間,角膜祖細胞或神經脊幹細胞(諸如在包含富潛能細胞之培養物中)可在存在DKK2之情況下培養,DKK2可以低至1 ng/ml、2 ng/ml、3 ng/ml、4 ng/ml、5 ng/ml、6 ng/ml或更低,或高達10 ng/ml、20 ng/ml、50 ng/ml、100 ng/ml、1 μg/ml、5 μg/ml、10 μg/ml、15 μg/ml或更高(諸如1 ng/ml-15 μg/ml、10 ng/ml-15 μg/ml、1 ng/ml-1 μg/ml、1 ng/ml-100 ng/ml、2 ng/ml-20 ng/ml或5 ng/ml-20 ng/ml,或較佳約10 ng/ml)之濃度存在於培養基中。
富潛能細胞或其他細胞(例如,角膜祖細胞或神經脊細胞)可與一或多種促進CEC增殖之因子一起培養。此類因子可在角膜內皮細胞之形成期間及/或之後包括於細胞之培養物中,且可包括含有胰島素及/或運鐵蛋白之EGF、NGF及ITS補充劑。
在一些實施例中,本發明之方法包含增加角膜內皮祖細胞中之至少一種選自由以下組成之群之轉錄因子之表現:ATF4、ATMIN、BHLHE40、CEBPD、CSRNP1、DRAP1、EGR1、ELF2、EMX2、ESRRA、ETS 2、FOS、FOSB、FOSL2、GTF3A、HIF1A、JUN、JUNB、JUND、KLF10、KLF9、MBD3、NFE2L1、NME2、NR1D1、NR4A1、PA2G4、POU3F3、RELA、TBX2、TFAP 2B、TFDP1、TSC22D1、USF2、YBX1、ZNF207、ZNF358及ZNF395,及在培養基中培養角膜祖細胞。
在一些實施例中,本發明之方法包含增加富潛能幹細胞(例如,誘導性富潛能幹細胞或胚胎幹細胞)中之至少一種選自由以下組成之群之轉錄因子之表現:ATF4、ATMIN、BHLHE40、CEBPD、CSRNP1、DRAP1、EGR1、ELF2、EMX2、ESRRA、ETS2、FOS、FOSB、FOSL2、GTF3A、HIF1A、JUN、JUNB、JUND、KLF10、KLF9、MBD3、NFE2L1、NME2、NR1D1、NR4A1、PA2G4、POU3F3、RELA、TBX2、TFAP2B、TFDP1、TSC22D1、USF2、YBX1、ZNF207、ZNF358及ZNF395,及在培養基中培養富潛能幹細胞。
在一些實施例中,在增加本文中所揭示之至少一種轉錄因子之表現之前,將角膜祖細胞培養至少2、3、4、5、6、7、8、9、10、11或12天或更長時間。在一些實施例中,在增加至少一種轉錄因子之表現之前,將角膜祖細胞培養至少8天。在一些實施例中,在增加至少一種轉錄因子之表現之前,將角膜祖細胞培養至少10天。在一些實施例中,在增加至少一種轉錄因子之表現之前,將角膜祖細胞培養至少12天。
在一些實施例中,在增加本文中所揭示之至少一種轉錄因子之表現之後,將角膜祖細胞培養至少2、4、6、8、10、12、14、16、18、20、22或24天或更長時間。在一些實施例中,在增加至少一種轉錄因子之表現之後,將角膜祖細胞培養至少2天。在一些實施例中,在增加至少一種轉錄因子之表現之後,將角膜祖細胞培養至少4天、至少10天、至少18天或至少24天。在一些實施例中,在增加至少一種轉錄因子之表現之後,將角膜祖細胞培養至少18天。
在一些實施例中,角膜祖細胞係衍生自富潛能幹細胞。適用於根據本文中所描述之方法將富潛能幹細胞分離、擴增及分化成角膜祖細胞之培養基包括(但不限於)StemFit Basic03培養基(Ajinomoto)、mTeSR1培養基、高葡萄糖達爾伯克氏改良伊格爾氏培養基(Dulbecco's Modified Eagle's Medium;DMEM)、DMEM/F-15 (Thermo Fisher#11330-032)、Liebovitz L-15、RPMI 1640、伊斯科夫氏改良達爾伯克氏培養基(Iscove's modified Dubelcco's media;IMDM)及Opti-MEM SFM ( Invitrogen Inc.)。化學成分確定的培養基包含最低必需培養基,諸如補充有人類血清白蛋白、人類Ex Cyte脂蛋白、運鐵蛋白、胰島素、維生素、必需及非必需胺基酸、丙酮酸鈉、麩醯胺酸及有絲分裂誘致劑之伊斯科夫氏改良達爾伯克氏培養基(IMDM)(Gibco)亦為適合的。如本文中所使用,有絲分裂原係指刺激細胞之細胞分裂的試劑。試劑可為化學物質,通常為某種形式之蛋白質,其促使細胞開始細胞分裂,從而觸發有絲分裂。在一個實施例中,考慮將無血清培養基(美國申請案第08/464,599號及PCT公開案第WO96/39487號;其各自以全文引用的方式併入本文中)及完全培養基(美國專利案第5,486,359號,其以全文引用的方式併入本文中)與本文中所描述之方法一起使用。在一些實施例中,培養基補充有10%胎牛血清(FBS)、人類自體血清、人類AB血清或補充有肝素(2 U/ml)之富含血小板的血漿。可將細胞培養物維持在CO
2氛圍(例如,5%至12%)中以維持培養液之pH值,在潮濕氛圍中在37℃下培育,且在角膜內皮祖細胞分化期間傳代以維持100%匯合。
可在足以維持富潛能性之培養基中培養待分化成角膜祖細胞或神經脊幹細胞之富潛能幹細胞。培養在本發明之某些態樣中產生之誘導性富潛能幹(iPS)細胞可使用為培養靈長類動物富潛能幹細胞,更特定言之,胚胎幹細胞而開發的各種培養基及技術(美國專利申請案第20070238170號及美國專利申請案第20030211603號;其各自以全文引用的方式併入本文中)。舉例而言,PSCs可在存在或不存在ROCK抑制劑之情況下維持於StemFit培養基或mTeSR1培養基中。與人類胚胎幹(hES)細胞相同,iPS細胞可維持在80% DMEM(Gibco #10829-018或#11965-092)、20%未熱滅活之確定胎牛血清(FBS)、1%非必需胺基酸、1 mM L-麩醯胺酸及0.1 mM β-巰基乙醇中。或者,ES細胞可維持在用80% Knock-Out DMEM(Gibco #10829-018)、20%血清替代物(Gibco #10828-028)、1%非必需胺基酸、1 mM L-麩醯胺酸及0.1 mM β-巰基乙醇製備之無血清培養基中。
在一些實施例中,培養富潛能幹細胞及誘導角膜祖細胞或神經脊幹細胞形成之方法包含在包含鹼性FGF、SB431542及諾金之分化培養基中培養富潛能幹細胞,藉此產生角膜內皮祖細胞,例如神經脊細胞。
在一些實施例中,培養富潛能幹細胞之方法包括在適合的基質,例如iMatrix 511 (Takara Bio, T304)上培養。
在一些實施例中,將富潛能幹細胞培養至少1、2、3、4、5、6、7、8、9、10或12天。
在一些實施例中,在增加本文中所揭示之至少一種轉錄因子之表現之前,將角膜祖細胞培養至少2、3、4、5、6、7、8、9、10、11或12天。在一些實施例中,在增加至少一種轉錄因子之表現之前,將角膜祖細胞培養至少8天。在一些實施例中,在增加至少一種轉錄因子之表現之前,將角膜祖細胞培養至少10天。在一些實施例中,在增加至少一種轉錄因子之表現之前,將角膜祖細胞培養至少12天。在一些實施例中,在增加至少一種轉錄因子之表現之前,在包含ROCK抑制劑(例如,Y27632)、人類FGF-鹼性SB431542、諾金、EGF及/或NGF之培養基中培養角膜內皮祖細胞。
在一些實施例中,在增加本文中所揭示之至少一種轉錄因子之表現之後,將角膜祖細胞培養至少2、4、6、8、10、12、14、16、18、20、22或24天或更長時間。在一些實施例中,在增加至少一種轉錄因子之表現之後,將角膜祖細胞培養至少2天。在一些實施例中,在增加至少一種轉錄因子之表現之後,將角膜祖細胞培養至少4天、至少10天、至少18天或至少24天。在一些實施例中,在增加至少一種轉錄因子之表現之後,將角膜祖細胞培養至少18天。
在一些實施例中,在增加至少一種轉錄因子之表現之前或之後,在包含EGF及/或NGF之培養基中培養角膜內皮祖細胞。
為了產生富潛能幹細胞衍生之角膜內皮祖細胞,在一些實施例中,收集富潛能細胞之單層且以例如2×10
5個細胞/cm
2之密度塗佈。藉由將富潛能幹細胞在存在或不存在ROCK抑制劑(若存在,則存在1、2或3天或更長時間)之情況下在培養基中培養至少1、2、3、4、5、6、7、8、9或10天來起始分化過程之步驟1。接著進行步驟2,將步驟1中獲得之細胞在具有FGF-2、SB431542及諾金中之一或多者之培養基中培養至少4、6、8或10天。接著進行步驟3,將步驟2中獲得之細胞在存在或不存在ROCK抑制劑之情況下,在包含EGF之培養基中培養至少1、2、3、4或5天。接著將細胞在包含一種EGF及NGF之培養基中培養至少1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29或30天。
適用於製備富潛能幹細胞衍生之角膜內皮祖細胞之培養基包括:
表 3 :成熟培養基 1
表 4 :成熟培養基 2
表 5 :成熟培養基 3
角膜內皮細胞標記物
組分及最終濃度 | 製造商 | 目錄號 | 針對500 ml |
Opti-MEM® I還原血清培養基 | Thermo Fisher Scientific | 31985-070 | 460 ml |
8%胎牛血清 | Hyclone | SH30070.03 | 40 ml |
氯化鈣,200 mg/L | Sigma-Aldrich | C5670-100G | 100 mg |
0.08%硫酸軟骨素A | Sigma-Aldrich | C9819-5G | 400 mg |
青黴素-鏈黴素 | Thermo Fisher Scientific | 15140-122 | 5 ml |
牛垂體提取物 | Alfa Aesar | J64417 | 50 mg |
表皮生長因子,5 ng/ml | Sigma | E9644-.2MG | 100 μl,5 μg/ml之儲備液 |
抗壞血酸,20 μg/ml | Sigma | A4403-100MG | 100 μl,20 mg/ml之儲備液 |
10 μM Y27632 | R&D system | 1254/10 | 100 μl,10 mM儲備液 |
組分及最終濃度 | 製造商 | 目錄號 | 針對500 ml |
Opti-MEM® I還原血清培養基 | ThermoFisher Scientific | 31985-070 | 460 ml |
8%胎牛血清 | Hyclone | SH30070.03 | 40 ml |
氯化鈣,200 mg/L | Sigma | C5670-100G | 100 mg |
0.08%硫酸軟骨素A | Sigma | C9819-5G | 400 mg |
青黴素-鏈黴素 | Thermo Fisher Scientific | 15140-122 | 5 ml |
表皮生長因子,5 ng/ml | Sigma | E9644-.2MG | 100 μl,5 μg/ml之儲備液 |
抗壞血酸,20 μg/ml | Sigma | A4403-100MG | 100 μl,20 mg/ml之儲備液 |
組分及最終濃度 | 製造商 | 目錄號 | 針對500 ml |
Opti-MEM® I還原血清培養基 | ThermoFisher Scientific | 31985-070 | 460 ml |
ITS補充劑 | Sigma | I3146 | 1 ml |
氯化鈣,200 mg/L | Sigma | C5670-100G | 100 mg |
0.08%硫酸軟骨素A | Sigma | C9819-5G | 400 mg |
青黴素-鏈黴素 | Thermo Fisher Scientific | 15140-122 | 5 ml |
表皮生長因子,5 ng/ml | Sigma | E9644-.2MG | 100 μl,5 μg/ml之儲備液 |
抗壞血酸,20 μg/ml | Sigma | A4403-100MG | 100 μl,20 mg/ml之儲備液 |
NGF,20 ng/ml | Peprotech | 450-01 | 100 μl,20 μg/ml之儲備液 |
可根據多種表現型準則來表徵CEC,例如成熟CEC。準則包括(但不限於)偵測或定量經表現之細胞標記物、泵活性、關於角膜修復之活體內功效及活體內角膜功能之改良,以及活體外及活體內移植後形態特性之表徵。
在本發明之某些態樣中獲得之CEC,例如成熟CEC具有形態特性,其特徵在於CEC之性質,諸如衍生自角膜。該等特性可由熟習此項技術者容易地理解且包括以下中之任一者或全部:在角膜之後表面上排列且面向眼睛之前房之富含粒線體之細胞(在活有機體中);形成具有明顯的六邊形形狀之大小均勻的細胞之單層之能力;形成允許溶質及營養物自眼房液滲漏至角膜之更淺的表層,同時以相反方向(自基質至眼房液)主動泵送水之「滲漏泵」之能力;及對氧化應力之抗性。單一細胞中存在的許多此等特性與該細胞為CEC譜系之成員一致。
本發明之CEC,例如成熟CEC亦可根據其是否表現作為CEC譜系之細胞之特徵的表現型標記物來表徵。例示性角膜內皮細胞標記物包括(但不限於):PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B、LMX1B、AQP1、ATP1A1、TJP1、NCAM1、CDH2、SLC4A4、CD166、POU6F2、CD248、MRGPRX3、KLF13、CA2、NBC1、N-鈣黏素Na+/K+ ATP酶、ZO-1、KLF13、膠原蛋白VIII、SLC16A3、CFTR、NBC1、CA2、AE2、SCL4A2、SCL16A1、CA12及CA4。CEC,例如成熟CEC可不表現NGFR、SOX10、HNK1、SSEA4、NANOG、OCT4、vWF及CD31 (後者存在於血管內皮細胞中)。CEC,例如成熟CEC可表現一或多種角膜內皮泵標記物(其包括:AQP1、CA2、CA4、CA12、SCL14A2、SLC16A1、SLC16A3、SLC16A7、CFTR、NHE1、ADCY10、電壓依賴性陰離子通道VDAC2及VDAC3、氯離子通道蛋白質CLCN2及CLC)、眼周神經脊標記物(其包括:PITX2及FOXC1)及/或細胞黏附及基質蛋白(其包括:緊連蛋白、連結蛋白43、9.3E抗原、膠原蛋白III、膠原蛋白IV、N鈣黏素、VE鈣黏素、E鈣黏素、β連環蛋白、p120、p190層黏連蛋白α4、巢蛋白-2及軸突引導因子4)。CEC,例如成熟CEC可表現至少一種角膜內皮泵標記物、至少一種眼周神經脊標記物以及至少一種細胞黏附及基質蛋白。
CEC標記物可包括表6中所提供之標記物中之任一者(mRNA序列提供為SEQ ID NO:98-140且胺基酸序列提供為SEQ ID NO:141-181)。
表 6
轉錄因子 | 寄存編號 | SEQ ID NO: | 寄存編號 | SEQ ID NO: |
SLC4A11 | NM_001174089.2 NM_032034.4 NM_001174090.2 NM_001363745.2 | 98 99 100 101 | NP_001167560.1 NP_114423.1 NP_001167561.1 NP_001350674.1 | 141 142 143 144 |
COL8A1 | NM_001850 NM_020351.4 | 102 103 | NP_001841.2 NP_065084.2 | 145 145 |
COL8A2 | NM_001294347.2 NM_005202.4 | 104 105 | NP_001281276.1 NP_005193.1 | 147 148 |
AQP1 | NM_001329872.2 NM_198098.4 | 106 107 | NP_001316801.1 NP_932766.1 | 149 150 |
ATP1A1 | NM_000701.8 NM_001160233.2 NM_001160234.2 | 108 109 110 | NP_000692.2 NP_001153705.1 NP_001153706.1 | 151 152 153 |
TJP1 | NM_001301025.3 NM_001301026.2 NM_001330239.4 NM_001355012.2 NM_001355013.1 NM_001355014.2 NM_001355015.2 NM_003257.5 NM_175610.4 | 111 112 113 114 115 116 117 118 119 | NP_001287954.2 NP_001287955.1 NP_001317168.1 NP_001341941.1 NP_001341942.1 NP_001341943.1 NP_001341944.1 NP_003248.3 NP_783297.2 | 154 155 156 157 158 159 160 161 162 |
NCAM1 | NM_000615.7 NM_001076682.4 NM_001242607.2 NM_001242608.2 NM_001386289.1 NM_001386290.1 NM_001386291.1 NM_001386292.1 NM_181351.5 | 120 121 122 123 124 125 126 127 128 | NP_000606.3 NP_001070150.1 NP_001229536.1 NP_001229537.1 NP_001373218.1 NP_001373219.1 NP_001373220.1 NP_001373221.1 NP_851996.2 | 163 164 165 166 167 168 169 170 171 |
CDH2 | NM_001308176.2 NM_001792.5 | 129 130 | NP_001295105.1 NP_001783.2 | 172 173 |
SLC4A4 | NM_001098484.3 NM_001134742.2 NM_003759.4 | 131 132 133 | NP_001091954.1 NP_001128214.1 NP_003750.1 | 174 175 176 |
CD166 (ALCAM) | NM_001243280.2 NM_001243281.2 NM_001243283.2 NM_001627.4 | 134 135 136 137 | NP_001230209.1 NP_001230210.1 NP_001230212.1 NP_001618.2 | 177 178 179 180 |
CD248 | NM_020404.3 | 138 | NP_065137.1 | 181 |
MRGPRX3 | NM_001370464.1 NM_054031.4 | 139 140 | NP_001357393.1 NP_473372.3 | 146 146 |
CEC,例如成熟CEC亦可顯示指示CEC成熟之整體基因表現圖譜。整體基因表現圖譜可與初生CEC或已知的成熟CEC之基因表現圖譜進行比較,且可藉由此項技術中已知之任何方法獲得,例如轉錄組學分析或微陣列分析。在一些實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本向CEC,例如成熟CEC之總轉錄本偏移至少1%、5%、10%、20%、30%、40%或50%。在一些實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本向CEC,例如成熟CEC之總轉錄本偏移至少1%。在一些實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本向CEC,例如成熟CEC之總轉錄本偏移至少5%。在一些實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本向CEC,例如成熟CEC之總轉錄本偏移至少10%。在一些實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本向CEC,例如成熟CEC之總轉錄本偏移至少20%。在一些實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本向CEC,例如成熟CEC之總轉錄本偏移至少30%。在一些實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本向CEC,例如成熟CEC之總轉錄本偏移至少40%。在一些實施例中,增加至少一種轉錄因子之表現使角膜內皮祖細胞之總轉錄本向CEC,例如成熟CEC之總轉錄本偏移至少50%。
可測定此類標記物在CEC,例如成熟CEC中之表現量之評估且與其他細胞(例如,初生CEC、角膜內皮祖細胞、神經脊細胞及血管內皮細胞)進行比較。CEC,例如成熟CEC之標記物之陽性對照物包括感興趣的物種之成年角膜內皮細胞,例如初生人類角膜內皮細胞。
本發明中列舉之組織特異性(例如,角膜內皮細胞特異性)蛋白質及寡醣決定子可使用任何適合的免疫技術偵測,諸如用於細胞表面標記物之流動式免疫細胞化學、用於細胞內或細胞表面標記物之免疫組織化學(例如,用於固定細胞或組織切片)、細胞提取物之西方墨點分析以及用於分泌至培養基中之細胞提取物或產物之酶聯免疫分析法。若在標準免疫細胞化學或流動式細胞測量術分析法中,視情況在固定細胞後且視情況使用經標記之二級抗體或其他結合物(諸如生物素-抗生物素蛋白結合物)擴增標記,顯著可偵測之量之抗體將與抗原結合,則細胞之抗原表現稱為「抗體可偵測」。
亦可在標準擴增方法中使用序列特異性引子,藉由北方墨點分析、點漬墨法雜交分析或即時聚合酶鏈反應(RT-PCR)在mRNA層面上偵測組織特異性(例如CEC,例如成熟CEC特異性)標記物之表現(美國專利案第5,843,780號)。本發明中列舉的特定標記物之序列資料可自公共資料庫,諸如GenBank獲得。若在典型受控實驗中根據標準程序對細胞樣品進行之分析法在標準時間窗內產生明顯可辨別的雜交或擴增產物,則根據本發明中所描述之分析法中之一者,在mRNA層面上之表現稱為「可偵測」。除非另有要求,否則若可藉由RT-PCR偵測到相應mRNA,則指示特定標記物之表現。若水準比對照細胞,諸如未分化的富潛能幹細胞、成纖維細胞或其他非相關細胞類型高至少2倍且較佳高超過10倍或50倍,則在蛋白質或mRNA層面上偵測到的組織特異性標記物之表現視為陽性的。
CEC,例如成熟CEC亦可根據其是否顯示形成「滲漏泵」之能力來表徵,該滲漏泵允許溶質及營養物自眼房液滲漏至角膜之更淺的表層,同時以相反方向(自基質至眼房液)主動泵送水。可藉由此項技術中已知的方法評估CEC之泵送功能,例如Mimuara等人, 2004 Investigative Opthamology and Visual Science, 45:9, 第2992-2997頁中所描述。為了測定衍生自富潛能幹細胞(例如誘導性富潛能幹細胞或胚胎幹細胞)或角膜內皮祖細胞之表現本發明之轉錄因子之CEC,例如成熟CEC中之泵送功能之變化,可將泵送功能與所培養之初生CEC (例如,人類)、未經修飾之角膜內皮祖細胞及/或未分化之細胞(富潛能幹細胞、神經脊幹細胞等)進行比較。添加烏本苷(ouabain) (Na/K ATP酶抑制劑)將消除泵送功能,且允許評估存在/不存在泵送功能。
亦可藉由對氧化應力之抗性之水準來表徵CEC,例如成熟CEC。對氧化應力之抗性可藉由qPCR來量測,以測定氧化應力途徑基因(NRF2、NOS2等)之表現量,及使用ROS生物標記物(諸如硝基酪胺酸及CellRox (CellROX™ Reagent Variety Pack,用於氧化應力偵測,Thermofisher C1044)藉由量測細胞中之反應性氧物質(ROS)含量來量測。可藉由此項技術中已知的方法評估對氧化應力之反應,例如Guha等人, 2017, Nature Scientific Reports, 4:4074 (DOI:10.1038/ s41598- 017- 03654-4)中所描述。為了測定衍生自富潛能幹細胞(例如,誘導性富潛能幹細胞或胚胎幹細胞)或角膜內皮祖細胞之表現本發明之轉錄因子之CEC之對氧化應力之抗性之變化,可將對氧化應力之抗性水準與所培養之初生CEC (例如,人類)、未經修飾之角膜內皮祖細胞及/或未分化之細胞(富潛能幹細胞、神經脊幹細胞等)進行比較。
CEC,例如成熟CEC之另一特性為其明顯的多邊形或六邊形形狀。
在另一態樣中,可評估CEC,例如成熟CEC在個體中移植及/或呈現長期存活的能力。在一個實施例中,為了測定CEC,例如成熟CEC是否在活體內存活且維持其表現型,向適當動物之角膜投與CEC (如本文中所描述)。在數天至數週或更長時間之時段之後收集角膜組織,以評估所投與之細胞之存在及表現型,例如使用人類特異性抗體藉由免疫組織化學或ELISA,或藉由RT-PCR分析。本發明中提供適用於在mRNA或蛋白質層面上評估基因表現之標記物。亦可藉由評估泵送功能或緊密接合區之標記物來測定對角膜功能之作用。
在一些實施例中,將CEC,例如成熟CEC移植至受體個體之角膜中。在一些實施例中,CEC,例如成熟CEC包含CEC,例如成熟CEC之群體,其中至少0.1%、0.2%、0.5%、1%、2%、3%、4%、5%、10%、20%、30%、40%、50%、60%、70%、80%、90%或100%的CEC,例如成熟CEC移植至受體個體之角膜中。
II. 本發明之細胞及組合物
本發明之另一態樣提供一種組合物,其包含例如根據本文中所描述之任何方法製備之CEC,例如成熟CEC之群體。本發明亦提供包含CEC,例如成熟CEC之群體之組合物,該CEC包含外源性轉錄因子或編碼轉錄因子之核酸。本發明亦提供包含富潛能幹細胞(例如,誘導性富潛能幹細胞或胚胎幹細胞)群體、神經脊幹細胞群體或角膜內皮祖細胞群體之組合物,該等細胞包含外源性轉錄因子或編碼轉錄因子之核酸。
在一些實施例中,組合物為經富集、純化或分離之CEC、神經脊幹細胞、角膜內皮祖細胞或富潛能幹細胞之群體,例如根據本文中所描述之任何方法製備。經富集、純化或分離之CEC、神經脊幹細胞、角膜內皮祖細胞或富潛能幹細胞之群體可為單一細胞懸浮液、聚集體、嵌合聚集體及/或結構,包括分支鏈結構及/或包囊。
在一些實施例中,CEC,例如成熟CEC之群體包含相對於CEC,例如成熟CEC之群體中之轉錄因子之內源性表現量增加的至少一種選自由以下組成之群之轉錄因子之表現量:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
在一些實施例中,增加之PITX2之表現包含相對於CEC群體中的PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少0.1倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少0.2倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少0.5倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少1倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少2倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少5倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少10倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少20倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少50倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少100倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少200倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少500倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少1,000倍。在一些實施例中,增加之PITX2之表現包含相對於CEC群體中之PITX2之內源性表現量增加至少10,000倍。在任何以上實施例中,CEC可為成熟CEC。
在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中的FOXC1之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少0.1倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少0.2倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少0.5倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少1倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少2倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少5倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少10倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少20倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少50倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少100倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少200倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少500倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少1,000倍。在一些實施例中,增加之FOXC1之表現包含相對於CEC群體中之FOXC1之內源性表現量增加至少10,000倍。在任何以上實施例中,CEC可為成熟CEC。
在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中的TFAP2B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少0.1倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少0.2倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少0.5倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少1倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少2倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少5倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少10倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少20倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少50倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少100倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少200倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少500倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少1,000倍。在一些實施例中,增加之TFAP2B之表現包含相對於CEC群體中之TFAP2B之內源性表現量增加至少10,000倍。在任何以上實施例中,CEC可為成熟CEC。
在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中的LMX1B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少0.1倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少0.2倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少0.5倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少1倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少2倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少5倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少10倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少20倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少50倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少100倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少200倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少500倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少1,000倍。在一些實施例中,增加之LMX1B之表現包含相對於CEC群體中之LMX1B之內源性表現量增加至少10,000倍。在任何以上實施例中,CEC可為成熟CEC。
在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中的POU6F2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少0.1倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少0.2倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少0.5倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少1倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少2倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少5倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少10倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少20倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少50倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少100倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少200倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少500倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少1,000倍。在一些實施例中,增加之POU6F2之表現包含相對於CEC群體中之POU6F2之內源性表現量增加至少10,000倍。在任何以上實施例中,CEC可為成熟CEC。
在一些實施例中,CEC,例如成熟CEC之群體進一步包含相對於CEC,例如成熟CEC之群體中的一或多種轉錄因子之內源性表現量增加的一或多種選自由以下組成之群之轉錄因子之表現量:ERG、ATF4、ATMIN、BHLHE40、CEBPD、CSRNP1、DRAP1、EGR1、ELF2、EMX2、ESRRA、ETS2、FOS、FOSB、FOSL2、GTF3A、HIF1A、JUN、JUN B、JUN D、KLF10、KLF9、MBD3、NFE2L1、NME2、NR1D1、NR4A1、PA2G4、POU3F3、RELA、TBX2、TFDP1、TSC22D1、USF2、YBX1、ZNF207、ZNF358及ZNF395。在一些實施例中,一或多種轉錄因子為ERG。在一些實施例中,一或多種轉錄因子為BHLHE40。在一些實施例中,一或多種轉錄因子為CEBPD。在一些實施例中,一或多種轉錄因子為CSRNP1。在一些實施例中,一或多種轉錄因子為EGR1。在一些實施例中,一或多種轉錄因子為ESRRA。在一些實施例中,一或多種轉錄因子為ETS2。在一些實施例中,一或多種轉錄因子為FOS。在一些實施例中,一或多種轉錄因子為FOSB。在一些實施例中,一或多種轉錄因子為FOSL2。在一些實施例中,一或多種轉錄因子為JUN。在一些實施例中,一或多種轉錄因子為JUNB。在一些實施例中,一或多種轉錄因子為JUND。在一些實施例中,一或多種轉錄因子為KLF10。在一些實施例中,一或多種轉錄因子為KLF9。在一些實施例中,一或多種轉錄因子為NR1D1。在一些實施例中,一或多種轉錄因子為NR4A1。在一些實施例中,一或多種轉錄因子為TSC22D1。
在一些實施例中,CEC群體為角膜內皮祖細胞群體。在一些實施例中,CEC群體為成熟CEC群體。在一些實施例中,CEC群體包含成熟CEC及角膜內皮祖細胞。
在一些實施例中,CEC群體之組合物包含約1×10
6個CEC至約1×10
12個CEC。在一些實施例中,CEC群體之組合物包含至少1×10
5、1×10
6、1×10
7、1×10
8、1×10
9、1×10
10、1×10
11或1×10
12個CEC。
本文中亦提供醫藥組合物及調配物,其包含CEC,例如成熟CEC或角膜內皮祖細胞及醫藥學上可接受之載劑。
在一些實施例中,醫藥組合物包含在約1×10
6個CEC至約1×10
12個CEC範圍內之劑量。在一些實施例中,劑量為約1×10
5 、1×10
6、1×10
7、1×10
8、1×10
9、1×10
10、1×10
11或1×10
12個CEC。在一些實施例中,醫藥組合物包含在約1×10
6個CEC至約1×10
12個CEC範圍內之劑量。
本發明之另一態樣提供一種包含富潛能幹細胞群體之組合物,該富潛能幹細胞群體包含表現載體,其中該表現載體包含編碼至少一種本發明之轉錄因子之核酸。
在一些實施例中,轉錄因子為PITX2、FOXC1、TFAP2B、LMX1B及POU6F2中之一或多者。在一些實施例中,轉錄因子為PITX2。在一些實施例中,轉錄因子為FOXC1。在一些實施例中,轉錄因子為TFAP2B。在一些實施例中,轉錄因子為LMX1B。在一些實施例中,轉錄因子為POU6F2。
在一些實施例中,富潛能幹細胞群體進一步包含表現載體,其包含編碼一或多種選自由以下組成之群之轉錄因子之核酸:ERG、ATF4、ATMIN、BHLHE40、CEBPD、CSRNP1、DRAP1、EGR1、ELF2、EMX2、ESRRA、ETS 2、FOS、FOSB、FOSL2、GTF3A、HIF1A、JUN、JUNB、JUND、KLF10、KLF9、MBD3、NFE2L1、NME2、NR1D1、NR4A1、PA2G4、POU3F3、RELA、TBX2、TFDP1、TSC22D1、USF2、YBX1、ZNF207、ZNF358及ZNF395。
在一些具體實例中,包含富潛能幹細胞群體之組合物包含約1×10
6個富潛能幹細胞至約1×10
12個富潛能幹細胞。在一些實施例中,包含富潛能幹細胞群體之組合物包含至少1×10
5、1×10
6、1×10
7、1×10
8、1×10
9、1×10
10、1×10
11或1×10
12個富潛能幹細胞。
在一些實施例中,富潛能幹細胞為胚胎幹細胞。在一些實施例中,富潛能幹細胞為誘導性富潛能幹細胞。
本發明之另一態樣提供包含角膜內皮祖細胞群體之組合物,該角膜內皮祖細胞群體包含表現載體,其中該表現載體包含編碼至少一種本發明之轉錄因子之核酸。
在一些實施例中,轉錄因子為PITX2、FOXC1、TFAP2B、LMX1B及POU6F2中之一或多者。在一些實施例中,轉錄因子為PITX2。在一些實施例中,轉錄因子為FOXC1。在一些實施例中,轉錄因子為TFAP2B。在一些實施例中,轉錄因子為LMX1B。在一些實施例中,轉錄因子為POU6F2。
在一些實施例中,角膜內皮祖細胞群體進一步包含表現載體,其包含編碼一或多種選自由以下組成之群之轉錄因子之核酸:ERG、ATF4、ATMIN、BHLHE40、CEBPD、CSRNP1、DRAP1、EGR1、ELF2、EMX2、ESRRA、ETS2、FOS、FOSB、FOSL2、GTF3A、HIF1A、JUN、JUNB、JUND、KLF10、KLF9、MBD3、NFE2L1、NME2、NR1D1、NR4A1、PA2G4、POU3F3、RELA、TBX2、TFDP1、TSC22D1、USF2、YBX1、ZNF207、ZNF358及ZNF395。
在一些實施例中,包含角膜內皮祖細胞群體之組合物包含約1×10
6個角膜內皮祖細胞至約1×10
12個角膜內皮祖細胞。在一些實施例中,包含角膜內皮祖細胞群體之組合物包含至少1×10
5、1×10
6、1×10
7、1×10
8、1×10
9、1×10
10、1×10
11或1×10
12個角膜內皮祖細胞。
本文中亦提供醫藥組合物及調配物,其包含角膜內皮祖細胞及醫藥學上可接受之載劑。
在一些實施例中,醫藥組合物包含在約1×10
6個角膜內皮祖細胞至約1×10
12個角膜內皮祖細胞範圍內之劑量。在一些實施例中,劑量為約1×10
5、1×10
6、1×10
7、1×10
8、1×10
9、1×10
10、1×10
11或1×10
12個角膜內皮祖細胞。在一些實施例中,醫藥組合物包含在約1×10
6個角膜內皮祖細胞至約1×10
12個角膜內皮祖細胞範圍內之劑量。
如本文中所描述之醫藥組合物及調配物可藉由以水性溶液形式混合CEC,例如成熟CEC與一或多種視情況選用之醫藥學上可接受之載劑(雷明頓氏醫藥科學(Remington's Pharmaceutical Sciences), 第22版, 2012;其以全文引用之方式併入本文中)來製備。醫藥學上可接受之載劑通常在使用劑量及濃度下對受體無毒性,且包括(但不限於):緩衝液,諸如磷酸鹽、檸檬酸鹽及其他有機酸;抗氧化劑,包括抗壞血酸及甲硫胺酸;防腐劑(諸如十八烷基二甲基苯甲基氯化銨;氯化六羥季銨;苯紮氯銨;苄索氯銨;酚、丁醇或苯甲醇;對羥基苯甲酸烷基酯,諸如對羥基苯甲酸甲酯或對羥基苯甲酸丙酯;兒茶酚;間苯二酚;環己醇;3-戊醇;及間甲酚);低分子量(小於約10個殘基)多肽;蛋白質,諸如血清白蛋白、明膠或免疫球蛋白;親水性聚合物,諸如聚乙烯吡咯啶酮;胺基酸,諸如甘胺酸、麩醯胺酸、天冬醯胺、組胺酸、精胺酸或離胺酸;單醣、雙醣及其他碳水化合物,包括葡萄糖、甘露糖或糊精;螯合劑,諸如EDTA;糖,諸如蔗糖、甘露醇、海藻糖或山梨醇;成鹽相對離子,諸如鈉;金屬錯合物(例如Zn-蛋白質錯合物);及/或非離子性界面活性劑,諸如聚乙二醇(PEG)。本文中之例示性醫藥學上可接受之載劑進一步包括間質藥物分散劑,諸如可溶性中性活性玻尿酸酶醣蛋白(sHASEGP),例如人類可溶性PH-20玻尿酸酶醣蛋白,諸如rHuPH20 (HYLENEX®, Baxter International, Inc.)。某些例示性sHASEGP及使用方法,包括rHuPH20,描述於美國專利公開案第2005/0260186號及第2006/0104968號中;其各自以全文引用的方式併入本文中。在一個態樣中,sHASEGP與一或多種其他葡萄糖胺聚糖酶(諸如軟骨素酶)組合。
在某些實施例中,包含CEC之組合物及醫藥組合物包含實質上純化的CEC群體。舉例而言,CEC之組合物可含有小於25%、20%、15%、10%、9%、8%、7%、6%、5%、4%、3%、2%或小於1%之除CEC以外的細胞。在一些實施例中,CEC之組合物含有小於25%、20%、15%、10%、9%、8%、7%、6%、5%、4%、3%、2%或小於1%之富潛能幹細胞。在另一實施例中,CEC之組合物中不含或偵測不到富潛能幹細胞。在一些實施例中,CEC之組合物含有小於25%、20%、15%、10%、9%、8%、7%、6%、5%、4%、3%、2%或小於1%之角膜內皮祖細胞。在另一實施例中,CEC之組合物中不含或偵測不到角膜內皮祖細胞。在一些實施例中,包含實質上純化的CEC群體之組合物為其中CEC占組合物中之細胞之至少約75%之組合物。在其他實施例中,實質上純化的CEC群體為其中CEC占該群體中之細胞之至少約80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、97.5%、98%、99%或甚至超過99%之群體。在任何實施例中,實質上純化的CEC群體可為實質上純化的成熟CEC群體。
III. 角膜內皮細胞之使用方法
藉由本文中所描述之方法產生之CEC,例如成熟CEC及醫藥組合物可用於眼部病症(包括角膜病症)之基於細胞之治療(其中需要角膜內皮細胞或將改良治療)。本文中描述使用由本發明提供之CEC,例如成熟CEC治療可受益於基於角膜內皮細胞之療法的各種病狀之方法。特定治療方案、投藥途徑及任何輔助療法將基於特定病狀、病狀之嚴重程度及患者之整體健康狀況來定製。此外,在某些實施例中,CEC,例如成熟CEC之投藥可有效地完全恢復角膜功能之損失或其他症狀。在其他實施例中,CEC,例如成熟CEC之投藥可有效地減輕症狀之嚴重程度及/或防止患者之病狀進一步惡化。本發明涵蓋包含CEC,例如成熟CEC之組合物之投藥可用於治療本文中所描述之任何病狀(包括完全或部分減輕症狀之嚴重程度)。
本發明涵蓋使用本文中所描述之任何方法獲得之CEC,例如成熟CEC (包括包含CEC,例如成熟CEC之組合物)可用於治療本文中所描述之任何適應症。此外,本發明涵蓋本文中所描述之任何包含CEC,例如成熟CEC之組合物可用於治療本文中所描述之任何適應症。
在一個實施例中,本發明提供用於預防及/或治療疾病,較佳影響角膜內皮細胞或可由角膜內皮細胞之移植或投藥治療之疾病之治療方法,該疾病包括例如原發性疾病,諸如法曲氏營養不良、虹膜角膜內皮症候群、後部多形性營養不良及先天性遺傳性內皮營養不良,及其中可使用更換角膜內皮作為有效治療為之繼發性疾病,包括角膜營養不良,或其中個體呈現引起大皰性角膜病變之角膜水腫之症狀、其中個體患有由使用隱形眼鏡或白內障手術引起之眼部損傷或其中個體正在考慮角膜移植及患有角膜移植中之晚期內皮衰竭。
在另一實施例中,本發明之CEC,例如成熟CEC可與其他治療性細胞或藥劑一起投與。CEC,例如成熟CEC可在組合或獨立調配物中同時投與,或依序投與。治療方法可包括投與免疫抑制劑。可使用之免疫抑制劑包括(但不限於)抗淋巴球球蛋白(ALG)多株抗體、抗胸腺細胞球蛋白(ATG)多株抗體、硫唑嘌呤、BASILIXIMAB® (抗IL-2R.α.受體抗體)、環孢素(環孢素A)、DACLIZUMAB® (抗IL-2R.α.受體抗體)、依維莫司(everolimus)、黴酚酸、RITUXIMAB® (抗CD20抗體)、西羅莫司(sirolimus)、他克莫司(tacrolimus)、黴酚酸酯(mycophemolate mofetil)、皮質類固醇及間質幹細胞。免疫抵製劑可以至少約1、2、4、5、6、7、8、9或10 mg/kg給藥。當使用免疫抵製劑時,其可全身性或局部投與,且其可在CEC,例如成熟CEC之投與之前、同時或之後投與。在投與細胞後,免疫抑制性療法可持續數週、數月、數年或無限期。舉例而言,在投與CEC,例如成熟CEC後,可向患者投與5 mg/kg之環孢素持續6週。此外,CEC,例如成熟CEC之組合物可包含免疫抑制劑,例如任何前述免疫抑制劑。
本發明之CEC,例如成熟CEC可與促進細胞黏附、移植及/或存活之藥劑一起投與。本發明之CEC可與ROCK抑制劑(例如,Y27632)及細胞外基質蛋白(例如,纖維結合蛋白)一起投與。本發明之CEC,例如成熟CEC可與一或多種抗細胞凋亡劑、消炎劑、抗氧化劑及細胞外基質蛋白(例如,纖維結合蛋白、層黏連蛋白、層黏連蛋白之經截短之E8片段(例如,iMatrix 511)、膠原蛋白(I、II、III、IV、VIII型等)等一起投與。
由本發明之方法及組合物提供之CEC,例如成熟CEC亦可用於各種應用。此等應用包括(但不限於)活體內移植或植入角膜內皮細胞;活體外篩選細胞毒性化合物、致癌物、誘變劑生長/調節因子或醫藥化合物;闡明角膜疾病及感染之機制;研究藥物及/或生長因子之作用機制;診斷及監測患者之癌症;基因療法;及製備生物活性產物。在一些實施例中,角膜內皮細胞包含成熟角膜內皮細胞、神經脊幹細胞、角膜內皮祖細胞或其組合。
測試化合物篩選
本發明之CEC,例如成熟CEC可用於篩選將影響本文中所提供之角膜內皮細胞之特徵之因子(諸如,溶劑、小分子藥物、肽及多核苷酸)或環境條件(諸如,培養條件或操作)。
在一些應用中,使用幹細胞(分化或未分化)篩選將促進細胞沿角膜內皮細胞譜系成熟或促進此類細胞在長期培養物中增殖及維持之因子。舉例而言,候選角膜內皮細胞成熟因子或生長因子係藉由將其添加至不同孔中之幹細胞中,且接著根據細胞之進一步培養及使用之所需準則測定所引起之任何表現型變化來測試。
本發明之特定篩選應用係關於藥物研究中之醫藥化合物之測試,例如
In vitroMethods in Pharmaceutical Research,
Academic Press, 1997及美國專利案第5,030,015號中所描述;其各自以全文引用的方式併入本文中。候選醫藥學化合物之活性之評估通常涉及將本發明之某些態樣中所提供之CEC,例如成熟CEC與候選化合物組合,測定可由化合物引起之細胞之形態、標記物表現型或代謝活性之任何變化(與未經處理之細胞或用惰性化合物處理之細胞相比),且接著將化合物之作用與所觀測之變化相關聯。進行篩選可能是因為該化合物經設計以對角膜內皮細胞具有藥理學作用,或因為經設計以在別處具有作用之化合物可能具有不希望的角膜副作用。可組合測試兩種或更多種藥物(藉由同時或依序與細胞組合),以偵測可能的藥物-藥物相互作用效果。
角膜療法及移植
本發明亦提供本文中所描述之CEC,例如成熟CEC之用途,其係用於恢復有需要之個體之眼睛功能之水準。
為了確定本文中所提供之CEC,例如成熟CEC對治療性應用之適用性,可首先在適合的動物模型中測試細胞。適合的動物包括兔CEC刮擦模型(Okumura等人, 2017 Am. J. Pathol., 2012, 181(1): 268-277)或猴CEC刮擦模型(Okumura等人, 2016, Nature Scientific Reports, 6:26113, DOI: 10.1038/srep26113)。其他適用於本發明之模型包括嚙齒動物模型,諸如費氏角膜內皮營養不良(Fuchs Endothelial Corneal Dystrophy)之L450W及Q455K Col8a2基因嵌入小鼠模型(Meng等人, 2013, Invest. Opthamol. Vis. Sci. 54(3):1887-189)及小鼠SLC4A11基因剔除模型(Groger等人, 2010, J. Biol. Chem., 285(19): 14467)。此類模型適用於評估CEC,例如成熟CEC在活體內存活及維持其表現型之能力。可向動物投與本文中所提供之CEC,例如成熟CEC。在數天至數週或更長時間之時段之後收集組織且進行評估。此可藉由向所投與之細胞提供可偵測標記(諸如綠色螢光蛋白或β-半乳糖苷酶);或藉由量測對所投與之細胞具有特異性的組成性標記物來進行。可使用人類特異性抗體藉由免疫組織化學或ELISA,或使用引子及引起對人類多核苷酸序列具有特異性的擴增之雜交條件藉由RT-PCR分析來評估投與嚙齒動物之人類CEC,例如成熟CEC之存在及表現型。本文中提供適用於在mRNA或蛋白質層面上評估基因表現之標記物。
本發明之說明本文中所描述之所需功能特性或動物模型中之功效的某些態樣中所提供之CEC,例如成熟CEC亦適用於直接投與患有角膜損傷之人類個體。在一個態樣中,本發明提供一種治療方法,其包含將經培養之CEC (例如,成熟CEC)或其前驅體之片狀物或單層或球狀物移植至有需要之個體之眼睛中,例如罹患角膜內皮細胞疾病之個體。舉例而言,可藉由移除後彈力膜來對個體之眼睛進行準備,且可將該經培養之CEC,例如成熟CEC之片狀物或單層或球狀物置放於該眼睛之前房中,例如與角膜後基質接觸(且較佳連接或附接)。視情況地,可在載體上提供CEC (例如,成熟CEC)或其前驅體之片狀物或單層或球狀物且投與患者之眼睛。
當僅角膜內皮受損時,一種臨床上較佳的治療為後彈力膜剝除伴內皮角膜成形術(DSEK),其包括移除患病的後彈力膜及角膜內皮且隨後移植供體組織。已研發出用於更換整個角膜(穿透性角膜移植或PK)或保留患者之後彈力膜及內皮且用供給組織更換其餘層(板層角膜移植)之程序。通常參見美國專利案第5,755,785號、美國專利案第5,649,944號、美國專利案第7,147,648號、美國專利案第7,300,653號、美國專利案第5,584,881號、美國專利案第5,686,414號、美國專利案第7,300,654號、美國專利申請案第10/525,391號,其各自以全文引用的方式併入本文中。正在研發角膜內皮手術更換之其他方法,包括後彈力膜內皮角膜成形術(DMEK),其中供體組織僅由後彈力膜及角膜內皮組成。可使用適當動物模型,例如本文中所描述之任何模型評估角膜內皮手術替代療法。本發明之某些態樣中提供之CEC,例如成熟CEC可用於角膜內皮重構,其中在移植之前在活體外培養CEC,例如成熟CEC。舉例而言,在聚合物上培養所供給之人類角膜細胞,釋放至生物黏著性明膠盤上,且接著成功地整合至經剝離之兔角膜中,其中明膠盤在移植之後溶解(Hsiue等人, Transplantation. 2006年2月, 15; 81(3):473-6,其以全文引用之方式併入本文中)。然而,利用所培養之細胞之方法需要具有該等細胞之來源,且因此受如上文所描述之缺乏適合的供給組織之影響。此外,由於供給細胞之差異,發現難以產生具有恆定的品質及功效之角膜內皮細胞培養物。由於可能需要對自各供體獲得之細胞進行廣泛的安全性及/或功效測試,因此監管障礙亦可能使此類方法在後勤方面難以大規模進行。此等及其他治療方法進一步描述於Thomas John, Corneal Endothelial Transplant: DSAEK, DMEK & DLEK (JP Medical Ltd, 2010)中,其以全文引用之方式併入本文中。
本發明之某些態樣中提供之CEC,例如成熟CEC可用於任何需要恢復或補充眼睛功能之個體的療法。適於此類療法之人類病狀包括原發性疾病,諸如法曲氏營養不良、虹膜角膜內皮症候群、後部多形性營養不良及先天性遺傳性內皮營養不良,及其中可使用更換角膜內皮作為有效治療為之繼發性疾病,包括角膜營養不良,或其中個體呈現引起大皰性角膜病變之角膜水腫之症狀、其中個體患有由使用隱形眼鏡或白內障手術引起之眼部損傷或其中個體正在考慮角膜移植。
對於人類療法,劑量通常在約10
9與10
12個細胞之間,且典型地在約5×10
9與5×10
10個細胞之間,根據個體之體重、病痛之性質及嚴重程度以及所投與之細胞的複製能力進行調節。
本發明亦提供本文中所揭示之CEC,例如成熟CEC的使用方法,例如與其他細胞類型組合作為類器官。類器官可自CEC建立且生長多個月,同時保留關鍵的形態、功能及基因表現特徵。
此外,出於製造、分配及使用目的,本發明之CEC,例如成熟CEC可以於等張賦形劑或培養基中之細胞培養物或懸浮液形式提供,視情況冷凍以有助於運輸或儲存。
本發明之組合物可呈適用於治療人類患者之調配物(諸如無熱原質或實質上無熱原質且無病原體)形式。當投與時,用於本發明之醫藥製劑可呈無熱原質、無病原體、生理學上可接受之形式。本發明之組合物可呈適於投與非人類獸醫哺乳動物(諸如犬、貓或馬)之調配物形式。
本發明亦包括不同的試劑系統,其包含在製造、分配或使用期間在任何時間存在之細胞的集合或組合。細胞集合包含兩種或更多種本發明中描述之細胞群體(例如,CEC,例如成熟CEC)、其前驅體及亞型之任何組合以及未分化之幹細胞、體細胞衍生之角膜內皮細胞或其他分化細胞類型。集合中之細胞群體有時共有相同的基因體或其經基因修飾之形式。
本發明涵蓋例如自人類富潛能幹細胞(例如,誘導性富潛能幹細胞、人類胚胎幹細胞或其他富潛能幹細胞)獲得之CEC,例如成熟CEC之組合物可用於治療任何前述疾病或病狀。此等疾病可用包含不同成熟程度之CEC的CEC (例如,成熟CEC)之組合物以及富集成熟CEC的CEC之組合物治療。
IV. 角膜內皮細胞之投藥方法
本發明之CEC,例如成熟CEC可藉由任何適用於所治療的疾病或病症之投藥途徑投與。在一個實施例中,本發明之CEC,例如成熟CEC可體表、全身或局部投與,諸如藉由注射,或作為裝置或植入物(例如,持續釋放型植入物)之一部分投與。舉例而言,當治療患有病症或疾病之患者時,可使用手術將本發明之CEC,例如成熟CEC移植至眼睛中,該病症或疾病諸如法曲氏營養不良、虹膜角膜內皮症候群、後部多形性營養不良及先天性遺傳性內皮營養不良,及可使用更換角膜內皮作為有效治療之繼發性疾病,包括角膜營養不良,或其中個體呈現引起大皰性角膜病變之角膜水腫之症狀、其中個體患有由使用隱形眼鏡或白內障手術引起之眼部損傷或其中個體考慮角膜移植,或黃斑變性、斯特格特氏病(Stargardt's disease)及色素性視網膜炎。熟習此項技術者將能夠確定用於所治療之疾病或病症之投藥途徑。
本發明之CEC,例如成熟CEC可在醫藥學上可接受之調配物中藉由注射來遞送。視本文中所描述之因素而定,用於注射之濃度可為有效且無毒之任何量。在一個實施例中,可向有需要之患者投與至少1×10
6、2×10
6、5×10
6、1×10
7、1×10
8或1×10
10個CEC,例如成熟CEC。
包含本發明之藥劑之產品及系統,諸如遞送媒劑,尤其調配為醫藥組合物之產品及系統,以及包含此類遞送媒劑及/或系統之套組,亦設想為本發明之一部分。
在某些實施例中,本發明之治療方法包括藉由植入物或裝置來投與本發明之CEC,例如成熟CEC之步驟。在某些實施例中,該裝置為用於治療本文中所描述之疾病或病狀的生物可侵蝕性植入物。
根據本文中所描述之方法投與之組合物之體積亦取決於諸如投藥模式、角膜內皮細胞之數目、患者之年齡以及所治療之疾病之類型及嚴重程度之因素。
通常將CEC,例如成熟CEC一次性遞送至患者。在患者之整個壽命期間,可遞送CEC,例如成熟CEC超過一次。在某些實施例中,在投與CEC,例如成熟CEC之前、同時或之後,亦向患者投與免疫抑制療法。在患者之整個生命中或在較短時段內,免疫抑制療法可能為必需的。免疫抑制療法之實例包括(但不限於)以下中之一或多者:抗淋巴球球蛋白(ALG)多株抗體、抗胸腺細胞球蛋白(ATG)多株抗體、硫唑嘌呤、BASILIXIMAB® (抗IL-2Ra受體抗體)、環孢素(環孢素A)、DACLIZUMAB® (抗IL-2Ra受體抗體)、依維莫司、黴酚酸、RITUX1MAB® (抗CD20抗體)、西羅莫司、他克莫司(Prograf™)及黴酚酸酯(MMF)。
在某些實施例中,將本發明之CEC,例如成熟CEC與醫藥學上可接受之載劑一起調配。舉例而言,CEC可單獨或作為醫藥調配物之組分投與。CEC,例如成熟CEC可經調配以用於以人類醫學之任何便利的方式投與。在某些實施例中,適用於腸胃外投藥之醫藥組合物可包含CEC,例如成熟CEC與以下之組合:一或多種醫藥學上可接受之無菌等張水性或非水性溶液、分散液、懸浮液或乳液,或可在臨用前復原成無菌可注射溶液或分散液之無菌粉末,其可含有抗氧化劑、緩衝液、抑菌劑、使調配物與所欲受體之血液等張之溶質或懸浮劑或增稠劑。可用於本發明之醫藥組合物中之適合的水性及非水性載體之實例包括水、乙醇、多元醇(諸如甘油、丙二醇、聚乙二醇及其類似物)及其適合的混合物。可例如藉由使用包衣材料(諸如卵磷脂)、在分散液之情況下藉由維持所需粒度及藉由使用界面活性劑來維持適當流動性。
V. 套組
本文中亦提供一種製品或套組,其包含本發明之CEC,例如成熟CEC之群體(例如,成熟CEC群體)及/或醫藥組合物。製品或套組可進一步包含藥品說明書,其包含使用本發明之角膜內皮細胞群體或醫藥組合物例如治療或延緩本文中所揭示之任何疾病之進程之說明。製品或套組可進一步包括自商業及使用者觀點來看所需之其他材料,包括其他緩衝液、稀釋劑、過濾器、針、注射器及具有使用說明書之藥品說明書。在一些實施例中,製品進一步包括一或多種其他藥劑(例如,化學治療劑)。本發明之角膜內皮細胞可與促進細胞黏附、移植及/或存活之藥劑一起投與。本發明之CEC,例如成熟CEC可與ROCK抑制劑(例如,Y27632)及細胞外基質蛋白(例如,纖維結合蛋白)一起投與。本發明之CEC,例如成熟CEC可與一或多種抗細胞凋亡劑、消炎劑、抗氧化劑及細胞外基質蛋白(例如,纖維結合蛋白、層黏連蛋白、層黏連蛋白之經截短之E8片段(例如,iMatrix 511)、膠原蛋白(I、II、III、IV、VIII型等)等一起投與。本發明之CEC,例如成熟CEC可與磁性珠粒或奈米粒子組合投與以促進CEC,例如成熟CEC之遞送。
用於一或多種藥劑之適合的容器包括例如瓶子、小瓶、袋子及注射器。
本文中所提及之所有公開案、專利申請案、專利案及其他參考文獻皆以全文引用之方式併入本文中。在存在衝突之情況下,以本說明書(包括定義)為準。此外,材料、方法及實例僅為說明性且不意欲為限制性。
實例 實例 1 : 材料及方法 慢病毒製備 :
使用pReceiver-Lv156 (GeneCopoeia)作為慢病毒載體以在EF1α啟動子下表現感興趣的基因。慢病毒粒子係使用由TakaraBio (www.takarabio.com)研發之一系列產品產生。病毒之封裝係使用第四代慢病毒封裝系統進行,該系統由Lenti-X 293T Cells (Takarabio,目錄號632180)及Lenti-X Packaging Single Shots (Takarabio,目錄號631275及631276)組成。病毒濃度及數量係分別使用Lenti-X™ Concentrator (Takarabio,目錄號631231及631232)及Lenti-X qRT-PCR Titration Kit (Takarabio,目錄號631235)測定。Lenti-X™ Concentrator為一種試劑,將其與病毒混合以在離心之後製備經濃縮之病毒原料,隨後使用Lenti-X qRT-PCR套組測定實際複本數目慢病毒基因體(數量),由此實際複本數目慢病毒基因體計算濃度。所有程序皆使用製造商推薦之方案進行。將病毒等分且儲存在-80℃下直至使用。
幹細胞培養物 :
在塗佈有iMatrix 511 (Takara T304)之6孔盤上,將人類iPSC維持於StemFit Basic03培養基(Ajinomoto)中。將細胞在20% O
2/5% CO
2之條件下培養且藉由用TrypLE-Select Enzyme (1x) (Thermo Fisher Scientific 12563011)解離成單細胞來每4-7天傳代一次。
角膜內皮細胞 (CEC) 分化方案 :
以三個步驟自培養皿獲得富潛能幹細胞衍生之角膜內皮細胞。在第一步驟中,使用TrypLE-Select Enzyme (1x) (Thermo Fisher Scientific 12563011)收集人類iPSC且以2×10
5個細胞/孔之密度塗佈於預塗有iMatrix511之6孔盤中。細胞用補充有10 μM Y27632之StemFit Basic03培養基培養24小時,接著在不存在Y27632之情況下在StemFit Basic03培養基中再培養2天。在第二步驟中,藉由在包含以下之培養基中培養來誘導神經脊細胞:DMEM/F-12 (Thermo Fisher Scientific 11330-032)、20% KnockOut™ Serum Replacement (Thermo Fisher Scientific 10828-028)、1% MEM非必需胺基酸溶液(Thermo Fisher Scientific 11140-050)、1% L-麩醯胺酸(Thermo Fisher Scientific 25030-081)、6 ng/ml之重組人類FGF-鹼性(Peprotech 100-18B)、0.007% 2-巰基乙醇、1 mM SB431542 (Stemgent 04-0010-10)、0.5 μg/ml之重組人類諾金(Peprotech 120-10C-100UG)及1%青黴素-鏈黴素(Thermo Fisher Scientific 15140-122)。每隔一天補充培養基持續6天。在第三步驟中,將細胞在包含以下之成熟培養基中培養24小時:Opti-MEM I還原血清培養基(Thermo Fisher Scientific 31985-070)、8%胎牛血清(Hyclone SH30070.03)、200 mg/L之氯化鈣(Sigma-Aldrich C5670-100G)、0.08%硫酸軟骨素A (Sigma-Aldrich C9819-5G)、10%牛垂體提取物(Alfa Aesar J64417)、5 ng/ml之表皮生長因子(Sigma-Aldrich E9644-.2MG)、20 μg/ml之抗壞血酸(Sigma-Aldrich A4403-100MG)、10 μM Y27632及1%青黴素-鏈黴素(Thermo Fisher Scientific 15140-122)。藉由在相同培養基中用IV型膠原蛋白酶(Stem Cell Technologies 07909)處理來使細胞以1:9之比率傳代。在傳代之後24小時,將培養基更換成包含以下之培養基(成熟培養基3):Opti-MEM I還原血清培養基(Thermo Fisher Scientific 31985-070)、ITS補充劑(Sigma-Aldrich I3146)、200 mg/L之氯化鈣(Sigma-Aldrich C5670-100G)、0.08%硫酸軟骨素A (Sigma-Aldrich C9819-5G)、5 ng/ml之表皮生長因子(Sigma-Aldrich E9644-.2MG)、20 μg/ml之NGF (Peprotech 450-01)、20 μg/ml之抗壞血酸(Sigma-Aldrich A4403-100MG)及1%青黴素-鏈黴素(Thermo Fisher Scientific 15140-122)。每隔一天更換培養基持續21天以形成iPSC衍生之CEC。圖1為分化方案之示意圖。在d10進行角膜內皮祖細胞之慢病毒感染,接著在如本文中及例如圖1中所描述之不同時間點獲得樣品以用於qPCR分析。D10時之細胞為誘導神經脊細胞分化後之細胞。不希望受理論約束,咸信轉導不限於在d10時進行。因此,可在替代性時間點進行轉導。作為非限制性實例,可在D7與D20之間的時間點,例如D7、D8、D9、D10、D11、D12、D13、D14、D15、D16、D17、D18、D19及D20,或D7與D18之間,或D7與D17之間,或D7與D16之間,或D7與D15之間,D7與D14之間,D7與D13之間,或D7與D12之間,或D7與D11之間,D7與D10之間,或D7與D9之間,或在D7之前,例如D0、D1、D2、D3、D4、D5或D6進行轉導,以成功地驅動CEC分化及成熟。
iPSC 衍生之 角膜內皮祖細胞之轉導 :
在分化過程中之d10,在成熟培養基3中,在存在聚凝胺(6 µg/µl)之情況下,進行用編碼轉錄因子之慢病毒粒子轉導iPSC衍生之角膜內皮祖細胞。在轉導之後兩天,將培養基更換成具有或不具有嘌呤黴素(0.5 µg/µl)之培養基。每隔一天更換培養基直至收集細胞溶解物以用於總RNA分離。
成熟角膜內皮細胞標記物之即時 PCR 分析 :
使用RNeasy Micro套組(Qiagen,目錄號#74004)分離來自iPSC衍生之CEC之總RNA,且用SuperScript VILO cDNA合成套組(Thermo Fisher Scientific 11754050)產生cDNA。使用Taqman探針(表7)及TaqMan Fast Advanced Master Mix (Thermo Fisher Scientific A44360),用QuantStudio 7 Flex機器(ThermoFisher)進行即時定量PCR反應。藉由delta Ct方法計算表現量,針對Pgk1 (2
- Δ Ct)標準化。
表 7
眼周間質(POM)為對Pitx2及FoxC1呈陽性之神經脊細胞之亞群。
實例 2 : 初生人類 CEC 中富集之轉錄因子同功型之鑑別
基因 | 標記物 | TaqMan ID |
SLC4A11 | 成熟CEC | Hs00984689_g1 |
COL8A1 | 未成熟/成熟CEC (在未成熟及成熟CEC上表現) | Hs00156669_m1 |
PITX2 | 前段發育中之TF (自POM階段至成熟CEC期間表現) | Hs04234069_Mh |
FOXC1 | 前段發育中之TF (自POM階段至成熟CEC期間表現) | Hs00559473_s1 |
TFAP2B | 前段發育中之TF (自POM階段至成熟CEC期間表現) | Hs01560931_m1 |
LMX1B | 前段發育中之TF (自POM階段至成熟CEC期間表現) | Hs00158750_m1 |
為了鑑別初生人類CEC中富集之轉錄因子特定同功型,自高通量基因表現資料(GSE41416)之綜合基因表現(Gene Expression OmnibusGEO)資料儲存庫下載由轉錄體分析產生之主體RNAseq資料。在DolphinNext伺服器上針對人類基因體hg19比對FastQ檔案。使用STAR-RSEM流水線,用生物資訊方案進行讀數之比對及列表。STAR映射器可在參考基因體上比對讀數且RSEM可定量基因及轉錄物之表現量。獲得各同功型之所預期的序列計數以及每百萬轉錄物(transcripts per million;tpm)且獲得同功型含量。接著,請求針對轉錄因子之表現量來查詢樣品。
在使用EBSeq軟體進行之第二分析中,在將所有成人樣品及所有胎兒樣品分別分組至「成人」及「胎兒」組中之後及在針對定序深度標準化之後分析同功型。圖5提供初生人類CEC中富集的本發明之特定轉錄因子之所有已知的同功型(主體RNAseq)。各細胞中之淡藍色條柱之長度指示表現量。
實例 3 : 分化 iPSC 衍生之 CEC 中之所引入的轉錄因子之表現
在分化之d10,用慢病毒(以與培養基呈1:10或1:50之體積比添加)轉導如以上實例1中所描述產生之iPSC-CEC以用於所選擇之轉錄因子同功型。PITX2 (P):NM_001204398及/或NM_000325,FOXC1 (F):NM_001453,TFAP2B (T):NM_003221,LMX1B (L):NM_002316。自分化之d12 (在轉導之後2天)進行嘌呤黴素(Puro)選擇。通常在iPSC衍生之CEC分化之d21進行qPCR分析;然而,可自約d14至約d28,例如d14、d15、d16、d17、d18、d19、d20或d21進行分析。與在不存在所添加之轉錄因子之情況下用GFP及聚凝胺處理之對照細胞相比,所引入的轉錄因子(PITX2、FOXC1、TFAP2B、LMX1B)上調。該上調在存在嘌呤黴素之情況下更顯著(參見圖2)。
實例 4 : 在轉錄因子引入之後中期 / 晚期 CEC 標記物之誘導
在分化之d10,用如實例1中所描述之慢病毒轉導如以上實例1中所描述產生之iPSC衍生之角膜內皮細胞以用於所選擇之轉錄因子同功型。在iPSC衍生之CEC分化之d21進行qPCR分析;然而,可自約d14至約d28進行分析。與在不存在所添加之轉錄因子之情況下用GFP及聚凝胺處理之對照細胞相比,存在於未成熟(例如,角膜內皮祖細胞)及成熟CEC上之標記物Col8a1以及成熟CEC之標記物Slc4a11上調,且在存在嘌呤黴素之情況下發生上調之增加(圖3)。與轉錄因子之組合無關地觀測到類似的上調。PITX2為唯一的包括於所有所測試之轉錄因子組合中之轉錄因子,表明PITX2為上調中期至晚期CEC標記物(諸如Col8a1及Slc4a11)以促進CEC成熟之關鍵轉錄因子。
實例 5 : 富潛能幹細胞衍生之包含增加之轉錄因子之表現的角膜內皮細胞之功能及形態分析
如實例1中詳細描述,使用分化過程產生富潛能幹細胞衍生之角膜內皮祖細胞。在針對成熟CEC分化之第10天,如實例1中所描述用慢病毒粒子轉導富潛能幹細胞衍生之CEC。接著,將細胞在成熟培養基中培養10天,如以上實例1中所描述。在細胞培養之第14天及第21天以及視情況地,第28天收集細胞。根據如本文中所描述之此項技術中已知的方法進行泵送功能、障壁功能及對氧化應力之抗性之功能活性分析法。
可藉由此項技術中已知的方法評估CEC (例如,成熟CEC)之泵送功能,例如Mimuara等人, 2004 Investigative Opthamology and Visual Science, 45:9, 第2992-2997頁中所描述。為了測定衍生自富潛能幹細胞或角膜內皮祖細胞之各自表現本發明之轉錄因子的成熟CEC之泵送功能之變化,與所培養之初生CEC (例如,人類)、未經修飾之角膜內皮祖細胞及/或未分化之細胞(富潛能幹細胞、神經脊幹細胞等)比較泵送功能。添加烏本苷(Na/K ATP酶抑制劑)將消除泵送功能,且允許評估存在/不存在泵送功能。
亦可藉由對氧化應力之抗性之水準來表徵成熟CEC。可藉由量測以下中之一或多者之數量來偵測氧化應力及/或DNA損傷之水準:核DNA損傷病灶;p21Cip1之表現量、p16INK4a之表現量;細胞球蛋白之表現量、GPX-1蛋白質之表現量,及8-羥基-2-脫氧鳥苷(8-OHdG)之含量。
對氧化應力之抗性亦藉由qPCR來量測,以測定氧化應力途徑基因(NRF2、NOS2等)之表現量,及使用ROS生物標記物(諸如硝基酪胺酸及CellRox (CellROX™ Reagent Variety Pack,用於氧化應力偵測,Thermofisher C1044)藉由量測細胞中之反應性氧物質(ROS)含量來量測。藉由此項技術中已知的方法評估對氧化應力之反應,例如Guha等人, 2017, Nature Scientific Reports, 4:4074 (DOI:10.1038/s41598 -017- 03654-4)中所描述。為了測定衍生自富潛能幹細胞或角膜內皮祖細胞之各自表現本發明之轉錄因子的CEC (例如,成熟CEC)之對氧化應力之抗性之變化,與所培養之初生CEC (例如,人類)、未經修飾之角膜內皮祖細胞及/或未分化之細胞(富潛能幹細胞、神經脊幹細胞等)比較對氧化應力之抗性之水準。
此外,藉由qPCR及免疫染色進行分析以確定CEC (例如,成熟CEC)是否表現指示角膜內皮細胞之標記物,包括Na+K+ATP酶泵、ZO-1及KLF13。此外,可分析使用如實例1中所描述之方法產生的CEC之血管內皮細胞標記物vWF及PECAM-1 (CD31)之表現(藉由qPCR及免疫染色來分析),以區分CEC細胞與血管內皮細胞。如圖6中所示,僅存在微量的vWF及CD31之RNA。
藉由使用特徵CEC形態(六邊形或多邊形形狀及彼此緊密黏附)之相差顯微圖進行觀測,分析使用如實例1及上文中所描述之方法產生之CEC。
實例 6 : 成熟 CEC 之活體內功效
本實例描述用於確定經移植之PSC衍生之成熟角膜內皮細胞之活體內功效之實驗。由符合GMP之臨床生產設施產生臨床級成熟富潛能幹細胞衍生之角膜內皮細胞。在最終釋放用於移植之成熟CEC懸浮液之前,對成熟CEC進行嚴格驗證及品質控制。每批成熟CEC經歷一系列品質控制安全性測試,包括針對無菌性、是否存在黴漿菌、是否存在內毒素、不存在富潛能幹細胞及核型分析之測試。藉由DNA指紋識別、適當的內皮形態及與CEC一致的標記物表現來確認一致性。關於包括特異性蛋白質之成熟CEC標記物(包括Na+K+ATP酶泵、ZO-1及KLF13)之可接受之水準及分佈,藉由免疫組織化學染色來測定純度。此外,根據經驗證的標準,藉由qRT-PCR來表徵各批料以說明hESC標記物(OCT-4、NANOG及SOX2)之下調以及成熟細胞標記基因(例如,PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B、LMX1B及MRGPRX3)之上調。
在非人類動物模型中使用根據本文中所描述之方法製備之成熟角膜內皮細胞,例如以確定用於人類用途之潛在安全性及/或功效。在非人類動物模型中使用細胞之醫藥組合物以評估CEC功能。適合的動物模型包括兔CEC刮擦模型(Okumura等人, Am. J. Pathol., 2012, 181(1): 268-277)或猴CEC刮擦模型(Okumura等人, 2016, Scientific Reports, 6:26113, DOI: 10.1038/srep26113)。其他適用於本發明之模型包括嚙齒動物模型,諸如費氏角膜內皮營養不良之L450W及Q455K Col8a2基因嵌入小鼠模型(Meng等人, 2013, Invest. Opthamol. Vis. Sci. 54(3):1887-189)及小鼠SLC4A11基因剔除模型(Groger等人, 2010, J. Biol. Chem., 285(19): 14467)。
可以手術方式向非人類動物之眼睛投與細胞(例如,以片狀物或懸浮液形式)。細胞亦可呈球狀物形式且以球狀物形式投與。舉例而言,成熟CEC組合物可用於兔模型中,如以下中之一或多者中所描述:Honda等人, Arch Ophthalmol. 2009年10月; 127(10):1321-6;Hitani等人, Mol Vis. 2008年1月3日; 14:1-9;Mimura等人, (Invest Ophthalmol Vis Sci. 2005; 46:3637-3644;Hsuie等人, Transplantation 2006; 81: 473-476;Lai等人, Transplantation 2007; 84: 1222-1232;Shimmura等人, Br J Ophthalmol 2005; 89:134-137;Chen等人, Molecular Vision 2011; 17:2148-2156;及Gospodrowicz等人, Proc. Natl. Acad. Sci. USA, 第76卷, 第1號, 第464-468頁, 1979年1月;及/或可用於嚙齒動物(例如,小鼠/大鼠)模型中,如上文及以下中所描述:Hayashi等人, Investigative Ophthalmology & Visual Science, 2009年7月, 第50卷, 第7號, 第3151-3158頁;Mimura等人, Experimental Eye Research 79 (2004) 231-237;Tchah, J Korean Med Sci. 1992 December; 7(4):337-42;及/或可用於非人類靈長類動物模型中,如以下中所描述:Koizumi等人, Invest Ophthalmol Vis Sci. 2007; 48:4519-4526);Koizumi等人, Cornea 2008; 27(增刊1):S48-S55;及/或用於人類或非人類中,如Peh等人, Transplantation. 2011年4月27日; 91(8):811-9中所描述。各前述公開案以全文引用之方式併入本文中。
針對移植至受體角膜上來評估以手術方式投與之經轉導以表現可偵測之標記物蛋白質(例如,GFP)之成熟人類CEC之活體內功效,例如藉由確認GFP表現及針對人類細胞核標記物進行免疫染色。評估在移植之後,供體成熟CEC之緊密連接區形成之功能標記物,例如ZO-1。可使用超音波測厚計(SP-3000;Tomey, Nagoya, Japan)藉由此項技術中已知之方法評估在投與成熟CEC後之角膜厚度(參見Xia等人, Investigative Opthamology and Visual Science)。可藉由偵測泵送功能之標記物(例如,SLC4A11、NA+/K+ ATP酶及SLC4A4)來評估泵送功能。角膜內皮細胞(例如,成熟角膜內皮細胞)中可表現之其他與泵送功能相關之標記物包括Na+/K+ ATP酶、AQP1、CA2、CA4、CA12、SCL14A2、SLC16A1、SLC16A3、SLC16A7、CFTR、NHE1、ADCY10、電壓依賴性陰離子通道VDAC2及VDAC3、氯離子通道蛋白質CLCN2及CLC。亦可藉由此項技術中已知的方法評估CEC (例如,成熟CEC)之泵送功能,例如Mimuara等人, 2004 Investigative Opthamology and Visual Science, 45:9, 第2992-2997頁中所描述。
將根據本文中所描述之方法製備之成熟角膜內皮細胞用於患者療法中,例如以如下方式:(i)患者最初接受免疫抑制治療(例如,類固醇);(ii)將患者視情況分配至治療組(例如,四個組,每組三名患者);(iii)向各組投與遞增劑量之細胞(較佳以單側方式,亦即,向各患者之一隻眼睛)。在移植後監測各患者之臨床過程,例如在移植後前6週內,且視情況在其他(先前或隨後)的時間點進行監測,較佳持續至少一年。患者之主要評估包括監測不良事件(AE)及劑量限制性毒性(DTL),包括用於偵測免疫介導之病理學、畸胎瘤形成及/或異常血管生長之分析法。亦評估患者之次要終點,包括關於眼內壓(IOP)、視力及/或移植物之內皮細胞計數之功效。長期隨訪較佳持續長達15年或更長時間以評估長期作用。由於自初始患者群組獲得令人滿意的安全性資料,進行其他患者之單側或雙側治療。此外,可向初始單側群組中之患者提供在先前未經治療之角膜中接受療法之機會。
圖 1為用於自富潛能幹細胞產生CEC,例如成熟CEC之方法之示意性說明。由hPSC誘導神經脊分化持續6天。在6天之後,將培養基更換成支持成熟之培養基。在第10天進行慢病毒感染,且藉由qPCR分析來自第14天及第21天(或來自約d14至約d28之樣品)之樣品的由所引入的慢病毒表現之轉錄因子之表現。
圖 2為一組條形圖,其展示在藉由用表現轉錄因子之慢病毒進行轉導來將轉錄因子(PITX2、FOXC1、TFAP2B及LMX1B)引入iPSC衍生之角膜內皮祖細胞之後的第21天時的此等轉錄因子之表現量。在iPSC衍生之CEC分化之第10天進行轉導且在分化之第21天進行qPCR分析。使用1:10或1:50之載體與培養基之體積比實現感染。與用綠色螢光蛋白(GFP)或聚凝胺處理之對照細胞相比,經轉導之細胞中之轉錄因子之表現量增加。
圖 3為一組條形圖,其展示在經表現PITX2、FOXC1、TFAP2B及LMX1B (單獨或以各種組合形式)之慢病毒轉導之角膜內皮祖細胞之CEC分化期間,COL8A1 (未成熟至成熟CEC之標記物)及Slc4a11 (成熟CEC之標記物)之表現量。使用1:10或1:50之載體與培養基之體積比實現感染。在iPSC衍生之CEC分化之第21天進行qPCR分析。與僅用GFP或聚凝胺處理之細胞相比,未成熟至成熟(COL8A1)及成熟(SLC4A11) CEC標記物上調。在存在嘌呤黴素(puromycin)之情況下,表現之增加更多。
圖 4為一組條形圖,其展示經表現轉錄因子之載體穩定感染之hPSC細胞株中的轉錄因子PITX2 (A)、FOXC1 (B)及TFAP2B (C)之表現。將轉錄因子單獨地或以與其他轉錄因子組合之形式引入。使用1:10或1:50之載體與培養基之體積比實現感染,接著進行嘌呤黴素選擇。條形圖D及E展示在經穩定感染之hPSC細胞株中之不同轉錄因子之表現增加後,未成熟至成熟CEC標記物COL8A1 (D)及成熟CEC標記物SLC4A11 (E)之表現。藉由qPCR分析來測定表現。與用單獨的GFP處理之對照細胞相比,經工程改造以表現一或多種轉錄因子之細胞中的COL8A1 (D)及成熟CEC標記物SLC4A11之表現量增加。
圖 5為呈現人類角膜內皮細胞中富集之轉錄因子同功型之表。
圖 6為一組條形圖,其展示根據如本文中所描述之方法產生的CEC細胞內之血管內皮標記物vWF及CD31之RNA表現量。
<![CDATA[<110> 美商安斯泰來再生醫藥協會(Astellas Institute for Regenerative Medicine)]]> <![CDATA[<120> 產生成熟角膜內皮細胞之方法]]> <![CDATA[<130> A1025.70063WO00]]> <![CDATA[<140> 還未指定]]> <![CDATA[<141> Concurrently Herewith]]> <![CDATA[<150> US 63/183,562]]> <![CDATA[<151> 2021-05-03]]> <![CDATA[<160> 185 ]]> <![CDATA[<170> PatentIn version 3.5]]> <![CDATA[<210> 1]]> <![CDATA[<211> 3110]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1]]> gcagtctgtg taagttttca tatctctgag tgtgtgcaca cagtggagag ggtggagcct 60 gccatcctca aatctgaaaa gattgagaga tttcagaggg cccagatgtg ccaaaggtca 120 gagggatcaa tatacaggcc ctaccacgga aaggcgggga aaaggttcga atagaaaact 180 gctgcagaag ggaagccact gagaggagca aatgtggact tgagggaaac tctctccccc 240 acccccactt ctatcccgtg caatttaata ccatcctcgc caggaacctt aacctcgtca 300 ttttaaaaaa tgagatatcc gtgacccagg gtgaacttgt tgaatgtagg tacagcagag 360 gaaattctag actctatgag cgtctgagcc ttgtccagtg caaacccttc gtgaacactg 420 ggtcagtgcg tggccgtgcc cacctgtgcg ccgacactct cagcatgcct ggtccacccg 480 ccttgacctc gggcgcggtg tcccagctaa gctgggccca gcgtcccggc cttccccagc 540 tgacaagcct agctcgttcg ctcccggctg tggccctccc accctctccc actagctcac 600 tccattcttc tagatttctc ttcactcatc ctctcccatc cccaccgcgc ccacctccac 660 tcccgccctc taccggtctc tcactttcct ccctccgcag tccctctttg ctgtgacctc 720 tttcctcaac tctgcaggcc tgaaagaagg tcacacacgc acgctcacac ccacactcca 780 cacgcctcgt cccaaacaac cccatgaaca ttgtcctttg ttccgtctct tgggccactt 840 tccctgtcgc ttcctcccag cccgtcctga tttgctcccc aaaagtacgt ttctgtctcc 900 ccgctgccct ggcgctcccc ctttgattta ttagggctgc cgggttggcg cagattgctt 960 tttcttctct tccatcccat cctcccttct ggtcctcctt tccacagtgg gagtccgtgc 1020 tcctgctcct cggttggctc ctaagtgccc cgccaggtcc cctctccttt cgctctcccg 1080 gctccggctc ccgactcttc ggcccgctgg catctgcttc cctcccctgc ctcgtttctc 1140 gtcgcccctg ctcgctcccc ccggcgctcg cccgggcgct gtgctcgctc ctggatcgcc 1200 agccgcgcag ccgggctcgg ccggccgccc gcgcgccact gtgcagtgga gtttggtgga 1260 atctctgctg acgtcacgtc actccccaca cggagtagga gcagagggaa gagagaggga 1320 tgagagggag ggagaggaga gagagtgcga gaccgagcga gaaagctgga gaggagcaga 1380 aagaaactgc cagtggcggc tagatttcgg aggccccagt gcacccgtgg actccttcgg 1440 aacttggcac cctcaggagc cctgcagtcc tctcaggccc ggctttcggg cgcttgccgt 1500 gcagccggag gctcggctcg ctggaaatcg ccccgggaag cagtgggacg cggagacagc 1560 agctctctcc cggtagccga taacggggaa tggagaccaa ctgccgcaaa ctggtgtcgg 1620 cgtgtgtgca attagagaaa gataaaagcc agcaggggaa gaatgaggac gtgggcgccg 1680 aggacccgtc taagaagaag cggcaaaggc ggcagcggac tcactttacc agccagcagc 1740 tccaggagct ggaggccact ttccagagga accgctaccc ggacatgtcc acacgcgaag 1800 aaatcgctgt gtggaccaac cttacggaag cccgagtccg ggtttggttc aagaatcgtc 1860 gggccaaatg gagaaagagg gagcgcaacc agcaggccga gctatgcaag aatggcttcg 1920 ggccgcagtt caatgggctc atgcagccct acgacgacat gtacccaggc tattcctaca 1980 acaactgggc cgccaagggc cttacatccg cctccctatc caccaagagc ttccccttct 2040 tcaactctat gaacgtcaac cccctgtcat cacagagcat gttttcccca cccaactcta 2100 tctcgtccat gagcatgtcg tccagcatgg tgccctcagc agtgacaggc gtcccgggct 2160 ccagtctcaa cagcctgaat aacttgaaca acctgagtag cccgtcgctg aattccgcgg 2220 tgccgacgcc tgcctgtcct tacgcgccgc cgactcctcc gtatgtttat agggacacgt 2280 gtaactcgag cctggccagc ctgagactga aagcaaagca gcactccagc ttcggctacg 2340 ccagcgtgca gaacccggcc tccaacctga gtgcttgcca gtatgcagtg gaccggcccg 2400 tgtgagccgc acccacagcg ccgggatcct aggaccttgc cggatggggc aactccgccc 2460 ttgaaagact gggaattatg ctagaaggtc gtgggcacta aagaaaggga gagaaagaga 2520 agctatatag agaaaaggaa accactgaat caaagagaga gctcctttga tttcaaaggg 2580 atgtcctcag tgtctgacat ctttcactac aagtatttct aacagttgca aggacacata 2640 cacaaacaaa tgtttgactg gatatgacat tttaacatta ctataagctt gttatttttt 2700 aagtttagca ttgttaacat ttaaatgact gaaaggatgt atatatatcg aaatgtcaaa 2760 ttaattttat aaaagcagtt gttagtaata tcacaacagt gtttttaaag gttaggcttt 2820 aaaataaagc atgttataca gaagcgatta ggatttttcg cttgcgagca agggagtgta 2880 tatactaaat gccacactgt atgtttctaa catattatta ttattataaa aaatgtgtga 2940 atatcagttt tagaatagtt tctctggtgg atgcaatgat gtttctgaaa ctgctatgta 3000 caacctaccc tgtgtataac atttcgtaca atattattgt tttacttttc agcaaatatg 3060 aaacaaatgt gttttatttc atgggagtaa aatatactgc atacaaaaaa 3110 <![CDATA[<210> 2]]> <![CDATA[<211> 3482]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 2]]> gcagtctgtg taagttttca tatctctgag tgtgtgcaca cagtggagag ggtggagcct 60 gccatcctca aatctgaaaa gattgagaga tttcagaggg cccagatgtg ccaaaggtca 120 gagggatcaa tatacaggcc ctaccacgga aaggcgggga aaaggttcga atagaaaact 180 gctgcagaag ggaagccact gagaggagca aatgtggact tgagggaaac tctctccccc 240 acccccactt ctatcccgtg caatttaata ccatcctcgc caggaacctt aacctcgtca 300 ttttaaaaaa tgagatatcc gtgacccagg gtgaacttgt tgaatgtagg tacagcagag 360 gaaattctag actctatgag cgtctgagcc ttgtccagtg caaacccttc gtgaacactg 420 ggtcagtgcg tggccgtgcc cacctgtgcg ccgacactct cagcatgcct ggtccacccg 480 ccttgacctc gggcgcggtg tcccagctaa gctgggccca gcgtcccggc cttccccagc 540 tgacaagcct agctcgttcg ctcccggctg tggccctccc accctctccc actagctcac 600 tccattcttc tagatttctc ttcactcatc ctctcccatc cccaccgcgc ccacctccac 660 tcccgccctc taccggtctc tcactttcct ccctccgcag tccctctttg ctgtgacctc 720 tttcctcaac tctgcaggcc tgaaagaagg tcacacacgc acgctcacac ccacactcca 780 cacgcctcgt cccaaacaac cccatgaaca ttgtcctttg ttccgtctct tgggccactt 840 tccctgtcgc ttcctcccag cccgtcctga tttgctcccc aaaagtacgt ttctgtctcc 900 ccgctgccct ggcgctcccc ctttgattta ttagggctgc cgggttggcg cagattgctt 960 tttcttctct tccatcccat cctcccttct ggtcctcctt tccacagtgg gagtccgtgc 1020 tcctgctcct cggttggctc ctaagtgccc cgccaggtcc cctctccttt cgctctcccg 1080 gctccggctc ccgactcttc ggcccgctgg catctgcttc cctcccctgc ctcgtttctc 1140 gtcgcccctg ctcgctcccc ccggcgctcg cccgggcgct gtgctcgctc ctggatcgcc 1200 agccgcgcag ccgggctcgg ccggccgccc gcgcgccact gtgcagtgga gtttggtgga 1260 atctctgctg acgtcacgtc actccccaca cggagtagga gcagagggaa gagagaggga 1320 tgagagggag ggagaggaga gagagtgcga gaccgagcga gaaagctgga gaggagcaga 1380 aagaaactgc cagtggcggc tagatttcgg aggccccagt gcacccgtgg actccttcgg 1440 aacttggcac cctcaggagc cctgcagtcc tctcaggccc ggctttcggg cgcttgccgt 1500 gcagccggag gctcggctcg ctggaaatcg ccccgggaag cagtgggacg cggagacagc 1560 agctctctcc cggtagccga atcactaaat ctggagccgc caaactgcta cttctgggcc 1620 cacgggccca caaggatcga atcggcagag tccccgcccg cgttctcgct agcgggtggg 1680 ggaaccgcct ggccgtcccc accctggatc cccacgccac agcgccgggc agcccctcct 1740 gtaggcagcg accttggcca gaggctcccc agggcccagc tcccttcagg agaggccgag 1800 acgcagggaa acgataacgg ggaatggaga ccaactgccg caaactggtg tcggcgtgtg 1860 tgcaattagg cgtgcagccg gcggccgttg aatgtctctt ctccaaagac tccgaaatca 1920 aaaaggtcga gttcacggac tctcctgaga gccgaaaaga ggcagccagc agcaagttct 1980 tcccgcggca gcatcctggc gccaatgaga aagataaaag ccagcagggg aagaatgagg 2040 acgtgggcgc cgaggacccg tctaagaaga agcggcaaag gcggcagcgg actcacttta 2100 ccagccagca gctccaggag ctggaggcca ctttccagag gaaccgctac ccggacatgt 2160 ccacacgcga agaaatcgct gtgtggacca accttacgga agcccgagtc cgggtttggt 2220 tcaagaatcg tcgggccaaa tggagaaaga gggagcgcaa ccagcaggcc gagctatgca 2280 agaatggctt cgggccgcag ttcaatgggc tcatgcagcc ctacgacgac atgtacccag 2340 gctattccta caacaactgg gccgccaagg gccttacatc cgcctcccta tccaccaaga 2400 gcttcccctt cttcaactct atgaacgtca accccctgtc atcacagagc atgttttccc 2460 cacccaactc tatctcgtcc atgagcatgt cgtccagcat ggtgccctca gcagtgacag 2520 gcgtcccggg ctccagtctc aacagcctga ataacttgaa caacctgagt agcccgtcgc 2580 tgaattccgc ggtgccgacg cctgcctgtc cttacgcgcc gccgactcct ccgtatgttt 2640 atagggacac gtgtaactcg agcctggcca gcctgagact gaaagcaaag cagcactcca 2700 gcttcggcta cgccagcgtg cagaacccgg cctccaacct gagtgcttgc cagtatgcag 2760 tggaccggcc cgtgtgagcc gcacccacag cgccgggatc ctaggacctt gccggatggg 2820 gcaactccgc ccttgaaaga ctgggaatta tgctagaagg tcgtgggcac taaagaaagg 2880 gagagaaaga gaagctatat agagaaaagg aaaccactga atcaaagaga gagctccttt 2940 gatttcaaag ggatgtcctc agtgtctgac atctttcact acaagtattt ctaacagttg 3000 caaggacaca tacacaaaca aatgtttgac tggatatgac attttaacat tactataagc 3060 ttgttatttt ttaagtttag cattgttaac atttaaatga ctgaaaggat gtatatatat 3120 cgaaatgtca aattaatttt ataaaagcag ttgttagtaa tatcacaaca gtgtttttaa 3180 aggttaggct ttaaaataaa gcatgttata cagaagcgat taggattttt cgcttgcgag 3240 caagggagtg tatatactaa atgccacact gtatgtttct aacatattat tattattata 3300 aaaaatgtgt gaatatcagt tttagaatag tttctctggt ggatgcaatg atgtttctga 3360 aactgctatg tacaacctac cctgtgtata acatttcgta caatattatt gttttacttt 3420 tcagcaaata tgaaacaaat gtgttttatt tcatgggagt aaaatatact gcatacaaaa 3480 aa 3482 <![CDATA[<210> 3]]> <![CDATA[<211> 1874]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 3]]> gcagtctgtg taagttttca tatctctgag tgtgtgcaca cagtggagag ggtggagcct 60 gccatcctca aatctgaaaa gattgagaga tttcagaggg cccagatgtg ccaaaggtca 120 gagggatcaa tatacaggcc ctaccacgga aaggcgggga aaaggttcga atagaaaact 180 gctgcagaag ggaagccact gagagataac ggggaatgga gaccaactgc cgcaaactgg 240 tgtcggcgtg tgtgcaatta ggcgtgcagc cggcggccgt tgaatgtctc ttctccaaag 300 actccgaaat caaaaaggtc gagttcacgg actctcctga gagccgaaaa gaggcagcca 360 gcagcaagtt cttcccgcgg cagcatcctg gcgccaatga gaaagataaa agccagcagg 420 ggaagaatga ggacgtgggc gccgaggacc cgtctaagaa gaagcggcaa aggcggcagc 480 ggactcactt taccagccag cagctccagg agctggaggc cactttccag aggaaccgct 540 acccggacat gtccacacgc gaagaaatcg ctgtgtggac caaccttacg gaagcccgag 600 tccgggtttg gttcaagaat cgtcgggcca aatggagaaa gagggagcgc aaccagcagg 660 ccgagctatg caagaatggc ttcgggccgc agttcaatgg gctcatgcag ccctacgacg 720 acatgtaccc aggctattcc tacaacaact gggccgccaa gggccttaca tccgcctccc 780 tatccaccaa gagcttcccc ttcttcaact ctatgaacgt caaccccctg tcatcacaga 840 gcatgttttc cccacccaac tctatctcgt ccatgagcat gtcgtccagc atggtgccct 900 cagcagtgac aggcgtcccg ggctccagtc tcaacagcct gaataacttg aacaacctga 960 gtagcccgtc gctgaattcc gcggtgccga cgcctgcctg tccttacgcg ccgccgactc 1020 ctccgtatgt ttatagggac acgtgtaact cgagcctggc cagcctgaga ctgaaagcaa 1080 agcagcactc cagcttcggc tacgccagcg tgcagaaccc ggcctccaac ctgagtgctt 1140 gccagtatgc agtggaccgg cccgtgtgag ccgcacccac agcgccggga tcctaggacc 1200 ttgccggatg gggcaactcc gcccttgaaa gactgggaat tatgctagaa ggtcgtgggc 1260 actaaagaaa gggagagaaa gagaagctat atagagaaaa ggaaaccact gaatcaaaga 1320 gagagctcct ttgatttcaa agggatgtcc tcagtgtctg acatctttca ctacaagtat 1380 ttctaacagt tgcaaggaca catacacaaa caaatgtttg actggatatg acattttaac 1440 attactataa gcttgttatt ttttaagttt agcattgtta acatttaaat gactgaaagg 1500 atgtatatat atcgaaatgt caaattaatt ttataaaagc agttgttagt aatatcacaa 1560 cagtgttttt aaaggttagg ctttaaaata aagcatgtta tacagaagcg attaggattt 1620 ttcgcttgcg agcaagggag tgtatatact aaatgccaca ctgtatgttt ctaacatatt 1680 attattatta taaaaaatgt gtgaatatca gttttagaat agtttctctg gtggatgcaa 1740 tgatgtttct gaaactgcta tgtacaacct accctgtgta taacatttcg tacaatatta 1800 ttgttttact tttcagcaaa tatgaaacaa atgtgtttta tttcatggga gtaaaatata 1860 ctgcatacaa aaaa 1874 <![CDATA[<210> 4]]> <![CDATA[<211> 1736]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 4]]> gcagtctgtg taagttttca tatctctgag tgtgtgcaca cagtggagag ggtggagcct 60 gccatcctca aatctgaaaa gattgagaga tttcagaggg cccagatgtg ccaaaggtca 120 gagggatcaa tatacaggcc ctaccacgga aaggcgggga aaaggttcga atagaaaact 180 gctgcagaag ggaagccact gagagataac ggggaatgga gaccaactgc cgcaaactgg 240 tgtcggcgtg tgtgcaatta gagaaagata aaagccagca ggggaagaat gaggacgtgg 300 gcgccgagga cccgtctaag aagaagcggc aaaggcggca gcggactcac tttaccagcc 360 agcagctcca ggagctggag gccactttcc agaggaaccg ctacccggac atgtccacac 420 gcgaagaaat cgctgtgtgg accaacctta cggaagcccg agtccgggtt tggttcaaga 480 atcgtcgggc caaatggaga aagagggagc gcaaccagca ggccgagcta tgcaagaatg 540 gcttcgggcc gcagttcaat gggctcatgc agccctacga cgacatgtac ccaggctatt 600 cctacaacaa ctgggccgcc aagggcctta catccgcctc cctatccacc aagagcttcc 660 ccttcttcaa ctctatgaac gtcaaccccc tgtcatcaca gagcatgttt tccccaccca 720 actctatctc gtccatgagc atgtcgtcca gcatggtgcc ctcagcagtg acaggcgtcc 780 cgggctccag tctcaacagc ctgaataact tgaacaacct gagtagcccg tcgctgaatt 840 ccgcggtgcc gacgcctgcc tgtccttacg cgccgccgac tcctccgtat gtttataggg 900 acacgtgtaa ctcgagcctg gccagcctga gactgaaagc aaagcagcac tccagcttcg 960 gctacgccag cgtgcagaac ccggcctcca acctgagtgc ttgccagtat gcagtggacc 1020 ggcccgtgtg agccgcaccc acagcgccgg gatcctagga ccttgccgga tggggcaact 1080 ccgcccttga aagactggga attatgctag aaggtcgtgg gcactaaaga aagggagaga 1140 aagagaagct atatagagaa aaggaaacca ctgaatcaaa gagagagctc ctttgatttc 1200 aaagggatgt cctcagtgtc tgacatcttt cactacaagt atttctaaca gttgcaagga 1260 cacatacaca aacaaatgtt tgactggata tgacatttta acattactat aagcttgtta 1320 ttttttaagt ttagcattgt taacatttaa atgactgaaa ggatgtatat atatcgaaat 1380 gtcaaattaa ttttataaaa gcagttgtta gtaatatcac aacagtgttt ttaaaggtta 1440 ggctttaaaa taaagcatgt tatacagaag cgattaggat ttttcgcttg cgagcaaggg 1500 agtgtatata ctaaatgcca cactgtatgt ttctaacata ttattattat tataaaaaat 1560 gtgtgaatat cagttttaga atagtttctc tggtggatgc aatgatgttt ctgaaactgc 1620 tatgtacaac ctaccctgtg tataacattt cgtacaatat tattgtttta cttttcagca 1680 aatatgaaac aaatgtgttt tatttcatgg gagtaaaata tactgcatac aaaaaa 1736 <![CDATA[<210> 5]]> <![CDATA[<211> 2294]]> <![CDATA[<212> DN]]>A <![CDATA[<213> 智人]]> <![CDATA[<400> ]]>5 ggagccgcag atctggtccg tcgctcgcct gggtgcctgg agctgagctg cggcaaggcc 60 cggctcctgt tcgaccgccc gaggggtgtg cgtgtgcgcg ttgcggaggg tgcgctcaga 120 gggccgcgtc gtggctgcag cggctgctgc cgccgcaggg gatctaatat cacctacctg 180 tccctgtcac tcttgacact tctctgtcag ggctgccgcg tggggggggg gcgggcagag 240 cgcggtcggc gttagctttc cttattggag gggttcttgg gggagggagg gagagaagaa 300 gggggtcttt gcccactctt gtttcgcttt ggagcttgga agcctgctcc ctaaagacgc 360 tctgagtggt gcccttctgc ccacatccca tgtcttcgtt tgcccgctga ctttccgtct 420 ccggactttt tcgcttgagc cttccggagg agacgggggc agcttggctt gagaactcgg 480 cgggggttgc gtcccctggc tctccccgca gcggggaaac tccgcgccta gagcgcgacc 540 cggagcgggc agcggcggct acgggggctc ggcggggcag tagccaagga ctagtagagc 600 gtcgcgctcc ctcgtccatg aactgcatga aaggcccgct tcacttggag caccgagcag 660 cggggaccaa gctgtcggcc gtctcctcat cttcctgtca ccatccccag ccgttagcca 720 tggcttcggt tctggctccc ggtcagcccc ggtcgctgga ctcctccaag cacaggctgg 780 aggtgcacac catctccgac acctccagcc cggaggccgc agagaaagat aaaagccagc 840 aggggaagaa tgaggacgtg ggcgccgagg acccgtctaa gaagaagcgg caaaggcggc 900 agcggactca ctttaccagc cagcagctcc aggagctgga ggccactttc cagaggaacc 960 gctacccgga catgtccaca cgcgaagaaa tcgctgtgtg gaccaacctt acggaagccc 1020 gagtccgggt ttggttcaag aatcgtcggg ccaaatggag aaagagggag cgcaaccagc 1080 aggccgagct atgcaagaat ggcttcgggc cgcagttcaa tgggctcatg cagccctacg 1140 acgacatgta cccaggctat tcctacaaca actgggccgc caagggcctt acatccgcct 1200 ccctatccac caagagcttc cccttcttca actctatgaa cgtcaacccc ctgtcatcac 1260 agagcatgtt ttccccaccc aactctatct cgtccatgag catgtcgtcc agcatggtgc 1320 cctcagcagt gacaggcgtc ccgggctcca gtctcaacag cctgaataac ttgaacaacc 1380 tgagtagccc gtcgctgaat tccgcggtgc cgacgcctgc ctgtccttac gcgccgccga 1440 ctcctccgta tgtttatagg gacacgtgta actcgagcct ggccagcctg agactgaaag 1500 caaagcagca ctccagcttc ggctacgcca gcgtgcagaa cccggcctcc aacctgagtg 1560 cttgccagta tgcagtggac cggcccgtgt gagccgcacc cacagcgccg ggatcctagg 1620 accttgccgg atggggcaac tccgcccttg aaagactggg aattatgcta gaaggtcgtg 1680 ggcactaaag aaagggagag aaagagaagc tatatagaga aaaggaaacc actgaatcaa 1740 agagagagct cctttgattt caaagggatg tcctcagtgt ctgacatctt tcactacaag 1800 tatttctaac agttgcaagg acacatacac aaacaaatgt ttgactggat atgacatttt 1860 aacattacta taagcttgtt attttttaag tttagcattg ttaacattta aatgactgaa 1920 aggatgtata tatatcgaaa tgtcaaatta attttataaa agcagttgtt agtaatatca 1980 caacagtgtt tttaaaggtt aggctttaaa ataaagcatg ttatacagaa gcgattagga 2040 tttttcgctt gcgagcaagg gagtgtatat actaaatgcc acactgtatg tttctaacat 2100 attattatta ttataaaaaa tgtgtgaata tcagttttag aatagtttct ctggtggatg 2160 caatgatgtt tctgaaactg ctatgtacaa cctaccctgt gtataacatt tcgtacaata 2220 ttattgtttt acttttcagc aaatatgaaa caaatgtgtt ttatttcatg ggagtaaaat 2280 atactgcata caaa 2294 <![CDATA[<210> 6]]> <![CDATA[<211> 3248]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 6]]> gcagtctgtg taagttttca tatctctgag tgtgtgcaca cagtggagag ggtggagcct 60 gccatcctca aatctgaaaa gattgagaga tttcagaggg cccagatgtg ccaaaggtca 120 gagggatcaa tatacaggcc ctaccacgga aaggcgggga aaaggttcga atagaaaact 180 gctgcagaag ggaagccact gagaggagca aatgtggact tgagggaaac tctctccccc 240 acccccactt ctatcccgtg caatttaata ccatcctcgc caggaacctt aacctcgtca 300 ttttaaaaaa tgagatatcc gtgacccagg gtgaacttgt tgaatgtagg tacagcagag 360 gaaattctag actctatgag cgtctgagcc ttgtccagtg caaacccttc gtgaacactg 420 ggtcagtgcg tggccgtgcc cacctgtgcg ccgacactct cagcatgcct ggtccacccg 480 ccttgacctc gggcgcggtg tcccagctaa gctgggccca gcgtcccggc cttccccagc 540 tgacaagcct agctcgttcg ctcccggctg tggccctccc accctctccc actagctcac 600 tccattcttc tagatttctc ttcactcatc ctctcccatc cccaccgcgc ccacctccac 660 tcccgccctc taccggtctc tcactttcct ccctccgcag tccctctttg ctgtgacctc 720 tttcctcaac tctgcaggcc tgaaagaagg tcacacacgc acgctcacac ccacactcca 780 cacgcctcgt cccaaacaac cccatgaaca ttgtcctttg ttccgtctct tgggccactt 840 tccctgtcgc ttcctcccag cccgtcctga tttgctcccc aaaagtacgt ttctgtctcc 900 ccgctgccct ggcgctcccc ctttgattta ttagggctgc cgggttggcg cagattgctt 960 tttcttctct tccatcccat cctcccttct ggtcctcctt tccacagtgg gagtccgtgc 1020 tcctgctcct cggttggctc ctaagtgccc cgccaggtcc cctctccttt cgctctcccg 1080 gctccggctc ccgactcttc ggcccgctgg catctgcttc cctcccctgc ctcgtttctc 1140 gtcgcccctg ctcgctcccc ccggcgctcg cccgggcgct gtgctcgctc ctggatcgcc 1200 agccgcgcag ccgggctcgg ccggccgccc gcgcgccact gtgcagtgga gtttggtgga 1260 atctctgctg acgtcacgtc actccccaca cggagtagga gcagagggaa gagagaggga 1320 tgagagggag ggagaggaga gagagtgcga gaccgagcga gaaagctgga gaggagcaga 1380 aagaaactgc cagtggcggc tagatttcgg aggccccagt gcacccgtgg actccttcgg 1440 aacttggcac cctcaggagc cctgcagtcc tctcaggccc ggctttcggg cgcttgccgt 1500 gcagccggag gctcggctcg ctggaaatcg ccccgggaag cagtgggacg cggagacagc 1560 agctctctcc cggtagccga taacggggaa tggagaccaa ctgccgcaaa ctggtgtcgg 1620 cgtgtgtgca attaggcgtg cagccggcgg ccgttgaatg tctcttctcc aaagactccg 1680 aaatcaaaaa ggtcgagttc acggactctc ctgagagccg aaaagaggca gccagcagca 1740 agttcttccc gcggcagcat cctggcgcca atgagaaaga taaaagccag caggggaaga 1800 atgaggacgt gggcgccgag gacccgtcta agaagaagcg gcaaaggcgg cagcggactc 1860 actttaccag ccagcagctc caggagctgg aggccacttt ccagaggaac cgctacccgg 1920 acatgtccac acgcgaagaa atcgctgtgt ggaccaacct tacggaagcc cgagtccggg 1980 tttggttcaa gaatcgtcgg gccaaatgga gaaagaggga gcgcaaccag caggccgagc 2040 tatgcaagaa tggcttcggg ccgcagttca atgggctcat gcagccctac gacgacatgt 2100 acccaggcta ttcctacaac aactgggccg ccaagggcct tacatccgcc tccctatcca 2160 ccaagagctt ccccttcttc aactctatga acgtcaaccc cctgtcatca cagagcatgt 2220 tttccccacc caactctatc tcgtccatga gcatgtcgtc cagcatggtg ccctcagcag 2280 tgacaggcgt cccgggctcc agtctcaaca gcctgaataa cttgaacaac ctgagtagcc 2340 cgtcgctgaa ttccgcggtg ccgacgcctg cctgtcctta cgcgccgccg actcctccgt 2400 atgtttatag ggacacgtgt aactcgagcc tggccagcct gagactgaaa gcaaagcagc 2460 actccagctt cggctacgcc agcgtgcaga acccggcctc caacctgagt gcttgccagt 2520 atgcagtgga ccggcccgtg tgagccgcac ccacagcgcc gggatcctag gaccttgccg 2580 gatggggcaa ctccgccctt gaaagactgg gaattatgct agaaggtcgt gggcactaaa 2640 gaaagggaga gaaagagaag ctatatagag aaaaggaaac cactgaatca aagagagagc 2700 tcctttgatt tcaaagggat gtcctcagtg tctgacatct ttcactacaa gtatttctaa 2760 cagttgcaag gacacataca caaacaaatg tttgactgga tatgacattt taacattact 2820 ataagcttgt tattttttaa gtttagcatt gttaacattt aaatgactga aaggatgtat 2880 atatatcgaa atgtcaaatt aattttataa aagcagttgt tagtaatatc acaacagtgt 2940 ttttaaaggt taggctttaa aataaagcat gttatacaga agcgattagg atttttcgct 3000 tgcgagcaag ggagtgtata tactaaatgc cacactgtat gtttctaaca tattattatt 3060 attataaaaa atgtgtgaat atcagtttta gaatagtttc tctggtggat gcaatgatgt 3120 ttctgaaact gctatgtaca acctaccctg tgtataacat ttcgtacaat attattgttt 3180 tacttttcag caaatatgaa acaaatgtgt tttatttcat gggagtaaaa tatactgcat 3240 acaaaaaa 3248 <![CDATA[<210> 7]]> <![CDATA[<211> 3983]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 7]]> gctcaaaagt tcagaagttt tcccaatgct tccttaagcg gctggcgcgc gagagaccga 60 gaaaaggtga cgcggggccc gggcaggcgg ccggcgcgcg gccccccccc cccccgccct 120 ggttatttgg ccgccttcgc cggcagctca gggcagagtc tcctggaagg cgcaggcagt 180 gtggcgagaa gggcgcctgc ttgttctttc tttttgtctg ctttcccccg tttgcgcctg 240 gaagctgcgc cgcgagttcc tgcaaggcgg tctgccgcgg ccgggcccgg ccttctcccc 300 tcgcagcgac cccgcctcgc ggccgcgcgg gccccgaggt agcccgaggc gccggaggag 360 ccagccccag cgagcgccgg gagaggcggc agcgcagccg gacgcacagc gcagcgggcc 420 ggcaccagct cggccgggcc cggactcgga ctcggcggcc ggcgcggcgc ggcccggccc 480 gagcgagggt ggggggcggc gggcggcgcg gggcggcggc gagcgggggc catgcaggcg 540 cgctactccg tgtccagccc caactccctg ggagtggtgc cctacctcgg cggcgagcag 600 agctactacc gcgcggcggc cgcggcggcc gggggcggct acaccgccat gccggccccc 660 atgagcgtgt actcgcaccc tgcgcacgcc gagcagtacc cgggcggcat ggcccgcgcc 720 tacgggccct acacgccgca gccgcagccc aaggacatgg tgaagccgcc ctatagctac 780 atcgcgctca tcaccatggc catccagaac gccccggaca agaagatcac cctgaacggc 840 atctaccagt tcatcatgga ccgcttcccc ttctaccggg acaacaagca gggctggcag 900 aacagcatcc gccacaacct ctcgctcaac gagtgcttcg tcaaggtgcc gcgcgacgac 960 aagaagccgg gcaagggcag ctactggacg ctggacccgg actcctacaa catgttcgag 1020 aacggcagct tcctgcggcg gcggcggcgc ttcaagaaga aggacgcggt gaaggacaag 1080 gaggagaagg acaggctgca cctcaaggag ccgcccccgc ccggccgcca gcccccgccc 1140 gcgccgccgg agcaggccga cggcaacgcg cccggtccgc agccgccgcc cgtgcgcatc 1200 caggacatca agaccgagaa cggtacgtgc ccctcgccgc cccagcccct gtccccggcc 1260 gccgccctgg gcagcggcag cgccgccgcg gtgcccaaga tcgagagccc cgacagcagc 1320 agcagcagcc tgtccagcgg gagcagcccc ccgggcagcc tgccgtcggc gcggccgctc 1380 agcctggacg gtgcggattc cgcgccgccg ccgcccgcgc cctccgcccc gccgccgcac 1440 catagccagg gcttcagcgt ggacaacatc atgacgtcgc tgcgggggtc gccgcagagc 1500 gcggccgcgg agctcagctc cggccttctg gcctcggcgg ccgcgtcctc gcgcgcgggg 1560 atcgcacccc cgctggcgct cggcgcctac tcgcccggcc agagctccct ctacagctcc 1620 ccctgcagcc agacctccag cgcgggcagc tcgggcggcg gcggcggcgg cgcgggggcc 1680 gcggggggcg cgggcggcgc cgggacctac cactgcaacc tgcaagccat gagcctgtac 1740 gcggccggcg agcgcggggg ccacttgcag ggcgcgcccg ggggcgcggg cggctcggcc 1800 gtggacgacc ccctgcccga ctactctctg cctccggtca ccagcagcag ctcgtcgtcc 1860 ctgagtcacg gcggcggcgg cggcggcggc gggggaggcc aggaggccgg ccaccaccct 1920 gcggcccacc aaggccgcct cacctcgtgg tacctgaacc aggcgggcgg agacctgggc 1980 cacttggcga gcgcggcggc ggcggcggcg gccgcaggct acccgggcca gcagcagaac 2040 ttccactcgg tgcgggagat gttcgagtca cagaggatcg gcttgaacaa ctctccagtg 2100 aacgggaata gtagctgtca aatggccttc ccttccagcc agtctctgta ccgcacgtcc 2160 ggagctttcg tctacgactg tagcaagttt tgacacaccc tcaaagccga actaaatcga 2220 accccaaagc aggaaaagct aaaggaaccc atcaaggcaa aatcgaaact aaaaaaaaaa 2280 aatccaatta aaaaaaaccc ctgagaatat tcaccacacc agcgaacaga atatccctcc 2340 aaaaattcag ctcaccagca ccagcacgaa gaaaactcta ttttcttaac cgattaattc 2400 agagccacct ccactttgcc ttgtctaaat aaacaaaccc gtaaactgtt ttatacagag 2460 acagcaaaat cttggtttat taaaggacag tgttactcca gataacacgt aagtttcttc 2520 ttgcttttca gagacctgct ttcccctcct cccgtctccc ctctcttgcc ttcttccttg 2580 cctctcacct gtaagatatt attttatcct atgttgaagg gagggggaaa gtccccgttt 2640 atgaaagtcg ctttcttttt attcatggac ttgttttaaa atgtaaattg caacatagta 2700 atttattttt aatttgtagt tggatgtcgt ggaccaaacg ccagaaagtg ttcccaaaac 2760 ctgacgttaa attgcctgaa actttaaatt gtgctttttt tctcattata aaaagggaaa 2820 ctgtattaat cttattctat cctcttttct ttctttttgt tgaacatatt cattgtttgt 2880 ttattaataa attaccattc agtttgaatg agacctatat gtctggatac tttaatagag 2940 ctttaattat tacgaaaaaa gatttcagag ataaaacact agaagttacc tattctccac 3000 ctaaatctct gaaaaatgga gaaaccctct gactagtcca tgtcaaattt tactaaaagt 3060 ctttttgttt agatttattt tcctgcagca tcttctgcaa aatgtactat atagtcagct 3120 tgctttgagg ctagtaaaaa gatatttttc taaacagatt ggagttggca tataaacaaa 3180 tacgttttct cactaatgac agtccatgat tcggaaattt taagcccatg aatcagccgc 3240 ggtcttacca cggtgatgcc tgtgtgccga gagatgggac tgtgcggcca gatatgcaca 3300 gataaatatt tggcttgtgt attccatata aaattgcagt gcatattata catccctgtg 3360 agccagatgc tgaatagata ttttcctatt atttcagtcc tttataaaag gaaaaataaa 3420 ccagttttta aatgtatgta tataattctc ccccatttac aatccttcat gtattacata 3480 gaaggattgc ttttttaaaa atatactgcg ggttggaaag ggatatttaa tctttgagaa 3540 actattttag aaaatatgtt tgtagaacaa ttatttttga aaaagattta aagcaataac 3600 aagaaggaag gcgagaggag cagaacattt tggtctaggg tggtttcttt ttaaaccatt 3660 ttttcttgtt aatttacagt taaacctagg ggacaatccg gattggccct cccccttttg 3720 taaataaccc aggaaatgta ataaattcat tatcttaggg tgatctgccc tgccaatcag 3780 actttgggga gatggcgatt tgattacaga cgttcggggg ggtggggggc ttgcagtttg 3840 ttttggagat aatacagttt cctgctatct gccgctccta tctagaggca acacttaagc 3900 agtaattgct gttgcttgtt gtcaaaattt gatcattgtt aaaggattgc tgcaaataaa 3960 tacactttaa tttcagtcaa aaa 3983 <![CDATA[<210> 8]]> <![CDATA[<211> 5631]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 8]]> agacatctgc tcctcacatg aatgcactca cctcctagag accaggctgc catcatgctc 60 tggaagcttg tggagaatgt caagtacgaa gatatctatg aggaccggca cgatggtgtc 120 ccgagccaca gctcgcggct ctcccagctg ggctcggtgt cccaaggacc ctactcgagc 180 gccccgccgc tgtcccacac cccgtcgtcg gacttccagc cgccctactt cccacccccc 240 taccagccgc tcccctacca ccagagccag gacccctact cccacgtcaa cgacccctac 300 tccctgaacc cactgcacca gccccagcaa catccctggg ggcaacggca gcggcaagaa 360 gtgggttcgg aagccggctc tctcctgccc cagcctcggg ccgccttgcc ccagctctcg 420 ggccttgacc cccggaggga ctaccactcg gtccgccggc cggacgtgct gctgcattcg 480 gcgcaccacg gcctggacgc gggcatgggt gacagcctct cgctgcacgg cctcggccat 540 cccggaatgg aagacgtcca gtcagttgaa gatgccaata acagcggcat gaatctattg 600 gaccagtctg tcattaaaaa agttccagtt cctcccaaat cggtgacttc tctaatgatg 660 aataaagacg gcttcctggg aggcatgtct gtcaacaccg gcgaggtgtt ttgctccgtc 720 ccaggccgtt tgtctctgct cagttcaact tcgaagtaca aagtaactgt gggagaagtt 780 cagagacggc tgtcgccccc tgaatgcctc aatgcatctc tcctcggcgg agtcctcaga 840 agagccaaat cgaaaaatgg ggggagatct ttgcgagaaa ggctagaaaa aatcggtttg 900 aatttacccg cgggcaggcg caaagcagca aatgtcacgt tactcacctc cctggtggaa 960 ggagaagctg ttcacttagc tagggatttt gggtacattt gcgaaacgga gtttcccgcc 1020 aaagccgtct ctgagtattt gaaccggcag cacacagacc cgagtgacct gcactcccga 1080 aagaatatgc tgttggccac caagcaactt tgtaaagaat ttacggatct actggcgcag 1140 gaccggacac cgatagggaa cagccgaccc agccccatcc tggagccggg gatccagagc 1200 tgcctcacgc acttcagcct catcacgcac ggcttcggcg ccccggccat ttgcgccgcg 1260 ctcacggccc tgcagaacta tctcaccgag gcgctcaaag gcatggacaa gatgttcttg 1320 aacaacacca ccactaacag gcacacgtct ggggaaggcc caggtagtaa aactggcgac 1380 aaggaggaga aacacaggaa atgaaaaatt tttaaaaaaa gaaggaaaaa tgttttaaat 1440 acaaaaggaa aaacagacaa aaatttaatt ttagctttaa aatattggat tggctttgga 1500 agaattatat taggtagaat acacatacaa tcaaaatttt aaaaaaaaaa gctaaataac 1560 ttaaaaaaaa actgaggcgt acaacggagc aacaatatcg gttctcagtg tctatttcaa 1620 gatacatttg gagacaaccg tccggatttt ccacttcggt tctttcgagt ttagtaatac 1680 tgataataaa agaaaaccat gatttcccct tccctttgga aaataaacat aagactaaac 1740 atgagaaaaa cgctaactta ttggaagaaa atcggagaaa cgttggtgtc aatgctttga 1800 gagctggttg actgagacgc acgaactttt taattttaaa tatattttta ggaaactctc 1860 gcagtccccg ccctccatct cacctcaccc gtctcccaac cacccttttc catgttaccc 1920 tcccttcctc acattgttac gggaatcttc tgggatgaaa atgagtgtgg ttggcccttt 1980 tgcgttgttt cagtcctctc ggtacctccc cgcccagccc tgcgatctta actcaccggg 2040 cccggctccc cggccgcttg cataattagg gagggcgagg gcggggcggg aggcctgtgg 2100 agaccaggcg gaggctgcaa tttttggtgc cggccggcag agcaggttct ggcggctgag 2160 gaaaatccgg accaataagt tgattcaaac atcatcagtt cctttcagaa atgttactag 2220 ctcccagcct tgccagcatc tgcatagaga gaatctcaca tttattatat ttgtgtcatc 2280 tactaatttt atgaactata gtaaaaaaaa aaaaacacac acacacacaa tatgaatacg 2340 ttgattagta tgtaattcct tcggaggggt atgtaccatt tcattctctt ctgttttcca 2400 aagctttgcc cgcatggttt atgagcttct tcaaagagga cttgggcttc ctacacaatc 2460 tataaggtac agagaaaaaa aaatccgatc cctttttaat caaagcctgt gtgtcagaat 2520 tctgcaggtg cacttcttta aagaagctca aagggaataa tttagaaagt ggccaatatg 2580 atggaagcag ctttgaatct acatgctaac attcctcaac actccaattc cggtggaggt 2640 ggcaggggag ggggtctgca aaatgaattt taagggaaaa gagtaaggat tcttagagcc 2700 ctatattcta atagtattgc cctgcattta aaattgattt gatttccctg ggttctttgg 2760 tgattgctgt ttaagcaagg aaagaagcag ctttacgagt ggacgtgggg aggagggcgg 2820 cacaagcacc cacatttctg taacaattgc tttcttacaa gatgctttat gaatgaggca 2880 tttttccctc ccagacgtgc acttgttttg gcatataatg gcaaaataat gcaaagtgaa 2940 gggagatgta tttcagcttt gatttttacc gtctggatac atcgggacta ttcccagtgg 3000 ataaagtttc atgcatttaa tatttctcac ttctggcagc ccagctcctt tcttgggctc 3060 catcttagca ttatcatgaa ataagatctg gaatccattg tctgcacctc cgcaaaagca 3120 gtgagaaatt atcccgggat aagggtgaat gagagaggtc tctaaatata gtgttgatac 3180 actcacctat ttaacaaagt agacgagatc tttgcaatac cccttaaaga taacgacata 3240 gatgttgttc tgcaggattt atagttagga cccactcaat tctccaggac tcccggtttt 3300 gcccccctcc cgctttgcct tggtgggggt ggggattggg ggagtgggga ttgcgttggg 3360 gttttaggaa tctgctgaga gctttgccca tttttattaa aagaggaaag ggaagttagg 3420 aagctcgtct caggtcacca aaagggccca agcaactgtt agggccacac tgcagcccat 3480 ctccaacccc tagcttcgtt tagcacttct gatcttcatg gcccagccct agaactgttg 3540 agaggaatgc aatggccaag agctagacgt tacggagagt gtagtcactc tcttttccca 3600 gctcagaggc ctgcgccttc gtccgagagc tcggccgatc gcattagatg tgttctgatt 3660 gcacaaggcc aggagagacc acactgaaaa cgatcgtctc ctttccttgc agggcaacgc 3720 gccccacgcg tgtgacgtgc gagagacgcg atggacgcgc cttgctctta ctgtgcaggt 3780 cctgagagcg tgtgggccac aggcgcccag tcgtgttgag gacatagaat cagccgctgg 3840 aggggctgcc gactgcgcgg gcccttcccg ctctcggtct caccctaagg gctaaggcga 3900 ccgagaaagc cccattctcc agtaggtaat ggggcggcgc ccggtgggct gcaggtgggg 3960 agggctccca gcgccgccag cggccacccg gggcgccggc tcctggaggg agagtggcct 4020 agaaatatcc aaggaatccg aagcttcccc tcctccacct ctgccagtac ggaaacaccc 4080 caccgtcaca atcctaaagc ggggagatgg gatgggaatt gtcttacttg gcaaggcagg 4140 gtaccttcat tgccagacgc cctcatttgt gtgttcctcc ttgctccagc gagatagaac 4200 cttttgcgcc cccaaccccg tttcgtggag tgagcccact accccttctc cctccctcac 4260 ttctcctttc atgtaggacc cccgccccct tgctttcctt agccaggccc gctacattta 4320 tctgataatt gagttattaa aagatttggt ttccttgggc ctataaatca ataaacagta 4380 ggattaacgc aatagtttgc cttttaagtc aagggagacg tttaaggcaa gcccctttga 4440 gctttgtttt caaaccaaac aggtgagttg cagctctccc cccggcccct gcactcttca 4500 gacatttggt ccctgcccac tcctaaacgc tcagtcccaa aacaaaatag cgaaagacag 4560 gaggagtcag gatgtggcag tgctgccttc acactttcca cttcgcaagt tcttttaaag 4620 gttccaaaga tctccagacc attctctgcc aaaccctgcc gcctcctgca cgtattgcag 4680 gtctctgggg agcaagaaat gtcctgtttg ggtgaggatt ccgtcaccta aaaagatctt 4740 taacttctcc cccaaagtgg gaaggtaact ttctccccct tttccccacc accttcactc 4800 ctacaccccc aattaccttg cattttcttt ccttccttct ggcctccaca cccatagctt 4860 tcctccatcc ccacttaaag aaccgaagag gcttttaaag acctggctgc tttgttttcc 4920 ttggccaagg aagccacttt ctctcaagca attatttcat atcctacgaa aactttggtc 4980 gaatggaaaa ctcgaaacct cgagcttatc tacacactgt tcctctgcta caatgctttc 5040 ctagttaaga gtgtttatag agaatttgtc atcacatctg atatcctgta cttgtaatac 5100 attatgtgga aaggaaataa ccttaaaccg tctgatgttg cctcaagagc ccaaacggcg 5160 tttccccacc tttgacgatg tatgtgaaat tactggctta aaaaaaaaag tatcaatttt 5220 tttttaacgg aatgaacact atccttcttt aaatgccaaa atcgactcca cctttgagtt 5280 ggtctctaat tctctaacat tgtttttgcc acacaatcaa gaaatatcaa tctattgact 5340 cttcacgaga agagctctgg agggtattca tgttaagttt gtatatattt atttatgctt 5400 aatttaatgg gaatgtgtaa atatggcgag caagtagttt gggattattt atctgtgaat 5460 ctatacctct gtgaatgggt ggttaaaaaa cctcttgacc ctagatagaa tcctatctga 5520 atttttctgt tctttataaa caagctgtta tggtaatggg tagaaattgg tttattgtcc 5580 agtgttaatc tgatttacat aaataaaaag attgttgtgt tttcatcttc a 5631 <![CDATA[<210> 9]]> <![CDATA[<211> 6324]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 9]]> agccccagct ctaaacccgg cggctcagcg ggcgcaccat ggcactggag tagcgcgggg 60 agcgcgcccg gagccccgcg gcccgctgcg ccccgcccgg gaccccgctg cgccgcgcgc 120 cccccccgcg gcccgcgggg ccgcccctgc acccccaccc cctcccccgc ctgccgccgc 180 cgccaccgcc accgccgccg ccgcctcctc cccgcggctc cgtctgcagc agccgccgcc 240 gccgggttcc gggactgaca agcaggtgac agaggagccg gcgcgcgtgg ctgcaagtgt 300 ccgggagagc gcggcgcggg ctgcagccgc cccggcccgc ccgcacgacg ccggggcccg 360 gggccagcgc gtcgccgctc cacgatcgcc gggggccggc gcaacccctg ccctgcgggg 420 gccgcgcctc cccggttcca gggccgcggc ggcggagagc gggtggacgg gccggcgggc 480 gagcagcccg gccggcgggg tccgcagcgc gccccgcgtc ccatggatat agcaacaggt 540 cccgagtcgc tggagaggtg cttccctcgc gggcagacgg actgcgccaa gatgttggac 600 ggcatcaaga tggaggagca cgccctgcgc cccgggcccg ccactctggg ggtgctgctg 660 ggctccgact gcccgcatcc cgccgtctgc gagggctgcc agcggcccat ctccgaccgc 720 ttcctgatgc gagtcaacga gtcgtcctgg cacgaggagt gtttgcagtg cgcggcgtgt 780 cagcaagccc tcaccaccag ctgctacttc cgggatcgga aactgtactg caaacaagac 840 taccaacagc tcttcgcggc caagtgcagc ggctgcatgg agaagatcgc ccccaccgag 900 ttcgtgatgc gggcgctgga gtgcgtgtac cacctgggct gcttctgctg ctgcgtgtgt 960 gaacggcagc tacgcaaggg cgacgaattc gtgctcaagg agggccagct gctgtgcaag 1020 ggtgactacg agaaggagaa ggacctgctc agctccgtga gccccgacga gtccgactcc 1080 gtgaagagcg aggatgaaga tggggacatg aagccggcca aggggcaggg cagtcagagc 1140 aagggcagcg gggatgacgg gaaggacccg cggaggccca agcgaccccg gaccatcctc 1200 accacgcagc agcgaagagc cttcaaggcc tccttcgagg tctcgtcgaa gccttgccga 1260 aaggtccgag agacactggc agctgagacg ggcctcagtg tgcgcgtggt ccaggtctgg 1320 tttcagaacc aaagagcaaa gatgaagaag ctggcgcggc ggcaccagca gcagcaggag 1380 cagcagaact cccagcggct gggccagggt gagccggggc cggggcaggg cctgggccag 1440 gaggtcctgt ccagccgcat ggagggcatg atggcttcct acacgccgct ggccccacca 1500 cagcagcaga tcgtggccat ggaacagagc ccctacggca gcagcgaccc cttccagcag 1560 ggcctcacgc cgccccaaat gccagggaac gactccatct tccatgacat cgacagcgat 1620 acctccttaa ccagcctcag cgactgcttc ctcggctcct cagacgtggg ctccctgcag 1680 gcccgcgtgg ggaaccccat cgaccggctc tactccatgc agagttccta cttcgcctcc 1740 tgagagccag ccaggcgcac ggacgcttgg gcaggggcct gggggggact gccagcctct 1800 gcggccagcc tggccacccc cgccctgctc tccgcacaga ctacagacag ccatacggtg 1860 ccctcccctc ggccagctgg gcctgaccac tgtgcccgtt gggtacagcc agaccggtag 1920 atgggcacag cctgggcagg ggctgtgtcc tgcccacaga gaccttgtca tccccaggga 1980 cccagagctc tcggacggcc actcgcctcc cagccccacc tcggcctcca tcgcctcctc 2040 cccatctctt ttttgggaag cttaaattct ctctattttt ttaaatgtcc tctctgtgtc 2100 catggccctc catgcaagcc ccaggacaat ggtgtcatga ggcggtgacc tgagaagcgt 2160 gtgtacctgt gccccagcaa gggcaggggt ggcctctggg ggcaggccca ctgcctggaa 2220 ccgcacaccc ctcagcctga gtctggagca gcagtggaga ggggcctgag gggaggcact 2280 gtcaggaggc gggctcggag cctgagcctg ggcaggcgca aagggacaga gaggcacgtg 2340 cagacacatg cacacttgca gacaaaccca cgcaaacaca cacacagctg tatggggaca 2400 ccagaaggga cagggatgct cagcgggtct gtcctgcctt gtcagaaaga gaaaaggagg 2460 ccaggcaggg gaccccccag ttcttaagag cgattggaaa gggaggaagg ggagaggaag 2520 aggcgaactt gaagcatcgg acccagttgt atcccagcct gggcccaaat gggggcagcc 2580 tgggcaggga gggcagcccc aggccccacc aactctagag gcagatggag cccccagaac 2640 caggtagcat cagaccagac aacagagcct ccaggggtca gggacttcag aagcacctgc 2700 tgggcacccc atctgcaatg tggtcctctc cccagccacc tctgcctccc ctcacatacc 2760 tccagtgaca aggagctcac taggtcagcg agcccacagc agctgtgctg tcctgcatcc 2820 cagagccagg cttccccagc tctccctctt aacactgtcc cccagcaggc ctccggctgt 2880 ccctctaaag gtgtggggca ggtatcactt caccttccca ctgatgtcag ccggccagaa 2940 gtgagcaggc acatcacctc tcctgctgtg gcacccttcc tctgttaatt tggcccaaaa 3000 gacaatgatt tggccacatg accttagaga ttcaccctgc cctgctgtag ctaaatccct 3060 gggccccaca cgcaagtgac agctaagcca catctgtttt ctgtgtatat gcaggatggg 3120 ggcacctact gttttgtttt gttttgtttt gttttgtttt gttttgtttt gttttgtttt 3180 gtttgagacg gagtttcgct cttgttgccc aggctggagt gcaatggcgc gatctcggct 3240 caccacaacc tccgcctccc aggttcaagt gattctgatg cctcagcctc cctagtagct 3300 gagattacag gcatgcgcca ccacacccag ctaattttgt atttttagta gcaacggggt 3360 ttctccatgt tggtcaggct ggtctccaac ccccgacctc aggtgatccg cctgcctcgg 3420 cctcccaaag tgctgggatt acaggcgtga gccaccgcac ccagtctgca cttactgttt 3480 agactgaatg agggaccgtg acctctttcc ttttccattc cttcttactc gattcattcc 3540 agcctgtgga atttctctgc accctgattc agtgaccact gctctcctct ctcccagcac 3600 atctgcccag tgaggagttg gccctgggtc tcacctgagg tgtgtggacc gggctggcct 3660 ctccctgttt gacattggcc cattaatgca tcctctttgg gggacacatt ccaattgcat 3720 ttcctgcccc cttctcccag ggcaattgca gaagattgtg tcaggcgccc tgctggaagt 3780 caggtgcact agatccatcc ccagccccag tctgctcaac tctatccctg tcagagcaag 3840 gaggctgggc tgctggggcc tgactggtga gcccaccctg tcccctggtg atcactgtgt 3900 ccccttgttc aggtgctcac aaccctacct ttaactctga ggtcaagccc taggccacca 3960 ccctaaagtc tgcctggtcc aacctttgag caagtaagga taatgaatgt cccttttcca 4020 cctttggggc cctctgcctg gatctctgga atcctctaag ttcaacctgt tctgtggttt 4080 tgctcccgtt tgctgggaaa ttcagtcccc ccagaatgtc ctgggccaac ctccttgcct 4140 gacatgtggc ctcgtgtcac ccattgggcc ccagcagcca gctagccctt ctgcagctct 4200 tcttacaaac agagcctctc caaggacctc agttgatgtt ctggtccttc tgccgcctca 4260 gcccaccagg gtccgtgcca ccatgggtct cttgagcagc agctgcactg gcttctggag 4320 agacacccct ctttctcctt ttgcacatgc accatctgaa tcgtgccagg gacatcctgg 4380 gcagattcag gggcagatgc cctatccccc aggagacctg gcccttctct ctcagaccca 4440 ataagttgga agggacgtca gaagcggtca tctcatctgc cccttatttt atagttggaa 4500 accctgaggc aagagaggga aagaggcctg tccaaggtcc gggttagtga cagagctgag 4560 ctgagaacag ggacgttgtg ccccactgtc ccctgtggtt tgtgaatgac ctccaggtca 4620 gggggtcaca acttgttctt agtaaacttg ccagctgttg gggtcacata ttcccattct 4680 ggggcctcac aaacccccga atccagccgg gaccccatgc caggagctgg tctagggaca 4740 gcatgcttgt gacccacaga ctgttaaagc cagaagggac ctcagagagt cccttatgct 4800 ggaggcgccc tgtcagccgt ggctaggggc cccttgctct atgctgtgcc ttgctgccca 4860 caggctccca gacaccagtg cccactctgc ccagccccgg actgggtgtg gctcgcagat 4920 gaacaagatg cagggcctgc cttgaggggt gtctcctaga aggaaagcca gactctccgg 4980 cccagccaga gagtccagac atggcaggga cccgtttctc agatgaggag cctgaggctc 5040 agagaaggga ggcgatgtgt tcagggccac ccagcagaag cctgtggggc tgggcaacct 5100 tctcccactt tatgggagga gctgcagcct tggctgggag ctgggcgggg agtagccagg 5160 accacccctt gcccgtgccg tgacatggaa ccttcatcac taagggggct ggagtgggaa 5220 gagggagata actgtgtggt ctccagagca aaagagaatg agaggtgggc agggggagtc 5280 ttggcaaaag accaagttcc acttccctgc tggggaagtc aaggctcaga aagaggaaat 5340 aattgcccca ggtaacacag ggcagaggag ggacaaaaag ctgggcatgg ccccagccag 5400 agcctcatct gcctactccg tgaagcctcc caggtactct gctatcctgg gaaacgcaca 5460 gggaggccac acagagacac tgctcacaag agtcagacca aggtgccagc acagcctgga 5520 aagagctcag aaagggggtt ggtgcacgtg gctgggcatc ttaggaggct tcctgagggt 5580 gggtaaaggt gggaaggccc tggcgctgca tcagatgagc agggcctggc agggacaagc 5640 ctcttctcct ttgggaagcc ctgcagcctc ctagcaagag gctgattccc cactctgccc 5700 ccatctgaat gtccttttca tgttgcacgc agggaacctc aggaaggagg attgcctgat 5760 gcctgcctgg ctccatcctt gagctctggg caccacctag ggtgagggag agcctgcagc 5820 tctggggcta agtctgccct ggggggaaag ggctccacgc tcacacgcac gcgctcgcac 5880 acacacactc acacctggac gcacacggag gcttgcggac ccatactcac aggcacatgt 5940 ggcctgggga ctgggggagc aggaaagacc cctccaacat ttggcccttg gaaggcacca 6000 ttgccaatga gcctctttgc tggttccccc gaccccacct gggggtccca tgggagccca 6060 gcccagccag gtgtggggat gggccaccgg ccattcctgt tttccttgta cagacagatt 6120 ctcactaccc acccgccatc cccagacaca ttttatttaa taacttgtca ttgttaaatt 6180 atttattagc gtttaccaca ccaccacccc caccctgccc tccactctca ccttccacct 6240 cttcccacaa cagcagaaaa tggaaacaac aacaaaaaaa gatgagacat cagtatattt 6300 gtaaataaac cgacctgtac actc 6324 <![CDATA[<210> 10]]> <![CDATA[<211> 6291]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 10]]> agccccagct ctaaacccgg cggctcagcg ggcgcaccat ggcactggag tagcgcgggg 60 agcgcgcccg gagccccgcg gcccgctgcg ccccgcccgg gaccccgctg cgccgcgcgc 120 cccccccgcg gcccgcgggg ccgcccctgc acccccaccc cctcccccgc ctgccgccgc 180 cgccaccgcc accgccgccg ccgcctcctc cccgcggctc cgtctgcagc agccgccgcc 240 gccgggttcc gggactgaca agcaggtgac agaggagccg gcgcgcgtgg ctgcaagtgt 300 ccgggagagc gcggcgcggg ctgcagccgc cccggcccgc ccgcacgacg ccggggcccg 360 gggccagcgc gtcgccgctc cacgatcgcc gggggccggc gcaacccctg ccctgcgggg 420 gccgcgcctc cccggttcca gggccgcggc ggcggagagc gggtggacgg gccggcgggc 480 gagcagcccg gccggcgggg tccgcagcgc gccccgcgtc ccatggatat agcaacaggt 540 cccgagtcgc tggagaggtg cttccctcgc gggcagacgg actgcgccaa gatgttggac 600 ggcatcaaga tggaggagca cgccctgcgc cccgggcccg ccactctggg ggtgctgctg 660 ggctccgact gcccgcatcc cgccgtctgc gagggctgcc agcggcccat ctccgaccgc 720 ttcctgatgc gagtcaacga gtcgtcctgg cacgaggagt gtttgcagtg cgcggcgtgt 780 cagcaagccc tcaccaccag ctgctacttc cgggatcgga aactgtactg caaacaagac 840 taccaacagc tcttcgcggc caagtgcagc ggctgcatgg agaagatcgc ccccaccgag 900 ttcgtgatgc gggcgctgga gtgcgtgtac cacctgggct gcttctgctg ctgcgtgtgt 960 gaacggcagc tacgcaaggg cgacgaattc gtgctcaagg agggccagct gctgtgcaag 1020 ggtgactacg agaaggagaa ggacctgctc agctccgtga gccccgacga gtccgactcc 1080 gtgaagagcg aggatgaaga tggggacatg aagccggcca aggggcaggg cagtcagagc 1140 aagggcagcg gggatgacgg gaaggacccg cggaggccca agcgaccccg gaccatcctc 1200 accacgcagc agcgaagagc cttcaaggcc tccttcgagg tctcgtcgaa gccttgccga 1260 aaggtccgag agacactggc agctgagacg ggcctcagtg tgcgcgtggt ccaggtctgg 1320 tttcagaacc aaagagcaaa gatgaagaag ctggcgcggc ggcaccagca gcagcaggag 1380 cagcagaact cccagcggct gggccaggag gtcctgtcca gccgcatgga gggcatgatg 1440 gcttcctaca cgccgctggc cccaccacag cagcagatcg tggccatgga acagagcccc 1500 tacggcagca gcgacccctt ccagcagggc ctcacgccgc cccaaatgcc agggaacgac 1560 tccatcttcc atgacatcga cagcgatacc tccttaacca gcctcagcga ctgcttcctc 1620 ggctcctcag acgtgggctc cctgcaggcc cgcgtgggga accccatcga ccggctctac 1680 tccatgcaga gttcctactt cgcctcctga gagccagcca ggcgcacgga cgcttgggca 1740 ggggcctggg ggggactgcc agcctctgcg gccagcctgg ccacccccgc cctgctctcc 1800 gcacagacta cagacagcca tacggtgccc tcccctcggc cagctgggcc tgaccactgt 1860 gcccgttggg tacagccaga ccggtagatg ggcacagcct gggcaggggc tgtgtcctgc 1920 ccacagagac cttgtcatcc ccagggaccc agagctctcg gacggccact cgcctcccag 1980 ccccacctcg gcctccatcg cctcctcccc atctcttttt tgggaagctt aaattctctc 2040 tattttttta aatgtcctct ctgtgtccat ggccctccat gcaagcccca ggacaatggt 2100 gtcatgaggc ggtgacctga gaagcgtgtg tacctgtgcc ccagcaaggg caggggtggc 2160 ctctgggggc aggcccactg cctggaaccg cacacccctc agcctgagtc tggagcagca 2220 gtggagaggg gcctgagggg aggcactgtc aggaggcggg ctcggagcct gagcctgggc 2280 aggcgcaaag ggacagagag gcacgtgcag acacatgcac acttgcagac aaacccacgc 2340 aaacacacac acagctgtat ggggacacca gaagggacag ggatgctcag cgggtctgtc 2400 ctgccttgtc agaaagagaa aaggaggcca ggcaggggac cccccagttc ttaagagcga 2460 ttggaaaggg aggaagggga gaggaagagg cgaacttgaa gcatcggacc cagttgtatc 2520 ccagcctggg cccaaatggg ggcagcctgg gcagggaggg cagccccagg ccccaccaac 2580 tctagaggca gatggagccc ccagaaccag gtagcatcag accagacaac agagcctcca 2640 ggggtcaggg acttcagaag cacctgctgg gcaccccatc tgcaatgtgg tcctctcccc 2700 agccacctct gcctcccctc acatacctcc agtgacaagg agctcactag gtcagcgagc 2760 ccacagcagc tgtgctgtcc tgcatcccag agccaggctt ccccagctct ccctcttaac 2820 actgtccccc agcaggcctc cggctgtccc tctaaaggtg tggggcaggt atcacttcac 2880 cttcccactg atgtcagccg gccagaagtg agcaggcaca tcacctctcc tgctgtggca 2940 cccttcctct gttaatttgg cccaaaagac aatgatttgg ccacatgacc ttagagattc 3000 accctgccct gctgtagcta aatccctggg ccccacacgc aagtgacagc taagccacat 3060 ctgttttctg tgtatatgca ggatgggggc acctactgtt ttgttttgtt ttgttttgtt 3120 ttgttttgtt ttgttttgtt ttgttttgtt tgagacggag tttcgctctt gttgcccagg 3180 ctggagtgca atggcgcgat ctcggctcac cacaacctcc gcctcccagg ttcaagtgat 3240 tctgatgcct cagcctccct agtagctgag attacaggca tgcgccacca cacccagcta 3300 attttgtatt tttagtagca acggggtttc tccatgttgg tcaggctggt ctccaacccc 3360 cgacctcagg tgatccgcct gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc 3420 accgcaccca gtctgcactt actgtttaga ctgaatgagg gaccgtgacc tctttccttt 3480 tccattcctt cttactcgat tcattccagc ctgtggaatt tctctgcacc ctgattcagt 3540 gaccactgct ctcctctctc ccagcacatc tgcccagtga ggagttggcc ctgggtctca 3600 cctgaggtgt gtggaccggg ctggcctctc cctgtttgac attggcccat taatgcatcc 3660 tctttggggg acacattcca attgcatttc ctgccccctt ctcccagggc aattgcagaa 3720 gattgtgtca ggcgccctgc tggaagtcag gtgcactaga tccatcccca gccccagtct 3780 gctcaactct atccctgtca gagcaaggag gctgggctgc tggggcctga ctggtgagcc 3840 caccctgtcc cctggtgatc actgtgtccc cttgttcagg tgctcacaac cctaccttta 3900 actctgaggt caagccctag gccaccaccc taaagtctgc ctggtccaac ctttgagcaa 3960 gtaaggataa tgaatgtccc ttttccacct ttggggccct ctgcctggat ctctggaatc 4020 ctctaagttc aacctgttct gtggttttgc tcccgtttgc tgggaaattc agtcccccca 4080 gaatgtcctg ggccaacctc cttgcctgac atgtggcctc gtgtcaccca ttgggcccca 4140 gcagccagct agcccttctg cagctcttct tacaaacaga gcctctccaa ggacctcagt 4200 tgatgttctg gtccttctgc cgcctcagcc caccagggtc cgtgccacca tgggtctctt 4260 gagcagcagc tgcactggct tctggagaga cacccctctt tctccttttg cacatgcacc 4320 atctgaatcg tgccagggac atcctgggca gattcagggg cagatgccct atcccccagg 4380 agacctggcc cttctctctc agacccaata agttggaagg gacgtcagaa gcggtcatct 4440 catctgcccc ttattttata gttggaaacc ctgaggcaag agagggaaag aggcctgtcc 4500 aaggtccggg ttagtgacag agctgagctg agaacaggga cgttgtgccc cactgtcccc 4560 tgtggtttgt gaatgacctc caggtcaggg ggtcacaact tgttcttagt aaacttgcca 4620 gctgttgggg tcacatattc ccattctggg gcctcacaaa cccccgaatc cagccgggac 4680 cccatgccag gagctggtct agggacagca tgcttgtgac ccacagactg ttaaagccag 4740 aagggacctc agagagtccc ttatgctgga ggcgccctgt cagccgtggc taggggcccc 4800 ttgctctatg ctgtgccttg ctgcccacag gctcccagac accagtgccc actctgccca 4860 gccccggact gggtgtggct cgcagatgaa caagatgcag ggcctgcctt gaggggtgtc 4920 tcctagaagg aaagccagac tctccggccc agccagagag tccagacatg gcagggaccc 4980 gtttctcaga tgaggagcct gaggctcaga gaagggaggc gatgtgttca gggccaccca 5040 gcagaagcct gtggggctgg gcaaccttct cccactttat gggaggagct gcagccttgg 5100 ctgggagctg ggcggggagt agccaggacc accccttgcc cgtgccgtga catggaacct 5160 tcatcactaa gggggctgga gtgggaagag ggagataact gtgtggtctc cagagcaaaa 5220 gagaatgaga ggtgggcagg gggagtcttg gcaaaagacc aagttccact tccctgctgg 5280 ggaagtcaag gctcagaaag aggaaataat tgccccaggt aacacagggc agaggaggga 5340 caaaaagctg ggcatggccc cagccagagc ctcatctgcc tactccgtga agcctcccag 5400 gtactctgct atcctgggaa acgcacaggg aggccacaca gagacactgc tcacaagagt 5460 cagaccaagg tgccagcaca gcctggaaag agctcagaaa gggggttggt gcacgtggct 5520 gggcatctta ggaggcttcc tgagggtggg taaaggtggg aaggccctgg cgctgcatca 5580 gatgagcagg gcctggcagg gacaagcctc ttctcctttg ggaagccctg cagcctccta 5640 gcaagaggct gattccccac tctgccccca tctgaatgtc cttttcatgt tgcacgcagg 5700 gaacctcagg aaggaggatt gcctgatgcc tgcctggctc catccttgag ctctgggcac 5760 cacctagggt gagggagagc ctgcagctct ggggctaagt ctgccctggg gggaaagggc 5820 tccacgctca cacgcacgcg ctcgcacaca cacactcaca cctggacgca cacggaggct 5880 tgcggaccca tactcacagg cacatgtggc ctggggactg ggggagcagg aaagacccct 5940 ccaacatttg gcccttggaa ggcaccattg ccaatgagcc tctttgctgg ttcccccgac 6000 cccacctggg ggtcccatgg gagcccagcc cagccaggtg tggggatggg ccaccggcca 6060 ttcctgtttt ccttgtacag acagattctc actacccacc cgccatcccc agacacattt 6120 tatttaataa cttgtcattg ttaaattatt tattagcgtt taccacacca ccacccccac 6180 cctgccctcc actctcacct tccacctctt cccacaacag cagaaaatgg aaacaacaac 6240 aaaaaaagat gagacatcag tatatttgta aataaaccga cctgtacact c 6291 <![CDATA[<210> 11]]> <![CDATA[<211> 6312]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 11]]> agccccagct ctaaacccgg cggctcagcg ggcgcaccat ggcactggag tagcgcgggg 60 agcgcgcccg gagccccgcg gcccgctgcg ccccgcccgg gaccccgctg cgccgcgcgc 120 cccccccgcg gcccgcgggg ccgcccctgc acccccaccc cctcccccgc ctgccgccgc 180 cgccaccgcc accgccgccg ccgcctcctc cccgcggctc cgtctgcagc agccgccgcc 240 gccgggttcc gggactgaca agcaggtgac agaggagccg gcgcgcgtgg ctgcaagtgt 300 ccgggagagc gcggcgcggg ctgcagccgc cccggcccgc ccgcacgacg ccggggcccg 360 gggccagcgc gtcgccgctc cacgatcgcc gggggccggc gcaacccctg ccctgcgggg 420 gccgcgcctc cccggttcca gggccgcggc ggcggagagc gggtggacgg gccggcgggc 480 gagcagcccg gccggcgggg tccgcagcgc gccccgcgtc ccatggatat agcaacaggt 540 cccgagtcgc tggagaggtg cttccctcgc gggcagacgg actgcgccaa gatgttggac 600 ggcatcaaga tggaggagca cgccctgcgc cccgggcccg ccactctggg ggtgctgctg 660 ggctccgact gcccgcatcc cgccgtctgc gagggctgcc agcggcccat ctccgaccgc 720 ttcctgatgc gagtcaacga gtcgtcctgg cacgaggagt gtttgcagtg cgcggcgtgt 780 cagcaagccc tcaccaccag ctgctacttc cgggatcgga aactgtactg caaacaagac 840 taccaacagc tcttcgcggc caagtgcagc ggctgcatgg agaagatcgc ccccaccgag 900 ttcgtgatgc gggcgctgga gtgcgtgtac cacctgggct gcttctgctg ctgcgtgtgt 960 gaacggcagc tacgcaaggg cgacgaattc gtgctcaagg agggccagct gctgtgcaag 1020 ggtgactacg agaaggagaa ggacctgctc agctccgtga gccccgacga gtccgactcc 1080 gtgaagagcg aggatgaaga tggggacatg aagccggcca aggggcaggg cagtcagagc 1140 aagggcagcg gggatgacgg gaaggacccg cggaggccca agcgaccccg gaccatcctc 1200 accacgcagc agcgaagagc cttcaaggcc tccttcgagg tctcgtcgaa gccttgccga 1260 aaggtccgag agacactggc agctgagacg ggcctcagtg tgcgcgtggt ccaggtctgg 1320 tttcagaacc aaagagcaaa gatgaagaag ctggcgcggc ggcaccagca gcagcaggag 1380 cagcagaact cccagcggct gggccaggag gtcctgtcca gccgcatgga gggcatgatg 1440 gcttcctaca cgccgctggc cccaccacag cagcagatcg tggccatgga acagagcccc 1500 tacggcagca gcgacccctt ccagcagggc ctcacgccgc cccaaatgcc aggtgaccac 1560 atgaacccct atgggaacga ctccatcttc catgacatcg acagcgatac ctccttaacc 1620 agcctcagcg actgcttcct cggctcctca gacgtgggct ccctgcaggc ccgcgtgggg 1680 aaccccatcg accggctcta ctccatgcag agttcctact tcgcctcctg agagccagcc 1740 aggcgcacgg acgcttgggc aggggcctgg gggggactgc cagcctctgc ggccagcctg 1800 gccacccccg ccctgctctc cgcacagact acagacagcc atacggtgcc ctcccctcgg 1860 ccagctgggc ctgaccactg tgcccgttgg gtacagccag accggtagat gggcacagcc 1920 tgggcagggg ctgtgtcctg cccacagaga ccttgtcatc cccagggacc cagagctctc 1980 ggacggccac tcgcctccca gccccacctc ggcctccatc gcctcctccc catctctttt 2040 ttgggaagct taaattctct ctattttttt aaatgtcctc tctgtgtcca tggccctcca 2100 tgcaagcccc aggacaatgg tgtcatgagg cggtgacctg agaagcgtgt gtacctgtgc 2160 cccagcaagg gcaggggtgg cctctggggg caggcccact gcctggaacc gcacacccct 2220 cagcctgagt ctggagcagc agtggagagg ggcctgaggg gaggcactgt caggaggcgg 2280 gctcggagcc tgagcctggg caggcgcaaa gggacagaga ggcacgtgca gacacatgca 2340 cacttgcaga caaacccacg caaacacaca cacagctgta tggggacacc agaagggaca 2400 gggatgctca gcgggtctgt cctgccttgt cagaaagaga aaaggaggcc aggcagggga 2460 ccccccagtt cttaagagcg attggaaagg gaggaagggg agaggaagag gcgaacttga 2520 agcatcggac ccagttgtat cccagcctgg gcccaaatgg gggcagcctg ggcagggagg 2580 gcagccccag gccccaccaa ctctagaggc agatggagcc cccagaacca ggtagcatca 2640 gaccagacaa cagagcctcc aggggtcagg gacttcagaa gcacctgctg ggcaccccat 2700 ctgcaatgtg gtcctctccc cagccacctc tgcctcccct cacatacctc cagtgacaag 2760 gagctcacta ggtcagcgag cccacagcag ctgtgctgtc ctgcatccca gagccaggct 2820 tccccagctc tccctcttaa cactgtcccc cagcaggcct ccggctgtcc ctctaaaggt 2880 gtggggcagg tatcacttca ccttcccact gatgtcagcc ggccagaagt gagcaggcac 2940 atcacctctc ctgctgtggc acccttcctc tgttaatttg gcccaaaaga caatgatttg 3000 gccacatgac cttagagatt caccctgccc tgctgtagct aaatccctgg gccccacacg 3060 caagtgacag ctaagccaca tctgttttct gtgtatatgc aggatggggg cacctactgt 3120 tttgttttgt tttgttttgt tttgttttgt tttgttttgt tttgttttgt ttgagacgga 3180 gtttcgctct tgttgcccag gctggagtgc aatggcgcga tctcggctca ccacaacctc 3240 cgcctcccag gttcaagtga ttctgatgcc tcagcctccc tagtagctga gattacaggc 3300 atgcgccacc acacccagct aattttgtat ttttagtagc aacggggttt ctccatgttg 3360 gtcaggctgg tctccaaccc ccgacctcag gtgatccgcc tgcctcggcc tcccaaagtg 3420 ctgggattac aggcgtgagc caccgcaccc agtctgcact tactgtttag actgaatgag 3480 ggaccgtgac ctctttcctt ttccattcct tcttactcga ttcattccag cctgtggaat 3540 ttctctgcac cctgattcag tgaccactgc tctcctctct cccagcacat ctgcccagtg 3600 aggagttggc cctgggtctc acctgaggtg tgtggaccgg gctggcctct ccctgtttga 3660 cattggccca ttaatgcatc ctctttgggg gacacattcc aattgcattt cctgccccct 3720 tctcccaggg caattgcaga agattgtgtc aggcgccctg ctggaagtca ggtgcactag 3780 atccatcccc agccccagtc tgctcaactc tatccctgtc agagcaagga ggctgggctg 3840 ctggggcctg actggtgagc ccaccctgtc ccctggtgat cactgtgtcc ccttgttcag 3900 gtgctcacaa ccctaccttt aactctgagg tcaagcccta ggccaccacc ctaaagtctg 3960 cctggtccaa cctttgagca agtaaggata atgaatgtcc cttttccacc tttggggccc 4020 tctgcctgga tctctggaat cctctaagtt caacctgttc tgtggttttg ctcccgtttg 4080 ctgggaaatt cagtcccccc agaatgtcct gggccaacct ccttgcctga catgtggcct 4140 cgtgtcaccc attgggcccc agcagccagc tagcccttct gcagctcttc ttacaaacag 4200 agcctctcca aggacctcag ttgatgttct ggtccttctg ccgcctcagc ccaccagggt 4260 ccgtgccacc atgggtctct tgagcagcag ctgcactggc ttctggagag acacccctct 4320 ttctcctttt gcacatgcac catctgaatc gtgccaggga catcctgggc agattcaggg 4380 gcagatgccc tatcccccag gagacctggc ccttctctct cagacccaat aagttggaag 4440 ggacgtcaga agcggtcatc tcatctgccc cttattttat agttggaaac cctgaggcaa 4500 gagagggaaa gaggcctgtc caaggtccgg gttagtgaca gagctgagct gagaacaggg 4560 acgttgtgcc ccactgtccc ctgtggtttg tgaatgacct ccaggtcagg gggtcacaac 4620 ttgttcttag taaacttgcc agctgttggg gtcacatatt cccattctgg ggcctcacaa 4680 acccccgaat ccagccggga ccccatgcca ggagctggtc tagggacagc atgcttgtga 4740 cccacagact gttaaagcca gaagggacct cagagagtcc cttatgctgg aggcgccctg 4800 tcagccgtgg ctaggggccc cttgctctat gctgtgcctt gctgcccaca ggctcccaga 4860 caccagtgcc cactctgccc agccccggac tgggtgtggc tcgcagatga acaagatgca 4920 gggcctgcct tgaggggtgt ctcctagaag gaaagccaga ctctccggcc cagccagaga 4980 gtccagacat ggcagggacc cgtttctcag atgaggagcc tgaggctcag agaagggagg 5040 cgatgtgttc agggccaccc agcagaagcc tgtggggctg ggcaaccttc tcccacttta 5100 tgggaggagc tgcagccttg gctgggagct gggcggggag tagccaggac caccccttgc 5160 ccgtgccgtg acatggaacc ttcatcacta agggggctgg agtgggaaga gggagataac 5220 tgtgtggtct ccagagcaaa agagaatgag aggtgggcag ggggagtctt ggcaaaagac 5280 caagttccac ttccctgctg gggaagtcaa ggctcagaaa gaggaaataa ttgccccagg 5340 taacacaggg cagaggaggg acaaaaagct gggcatggcc ccagccagag cctcatctgc 5400 ctactccgtg aagcctccca ggtactctgc tatcctggga aacgcacagg gaggccacac 5460 agagacactg ctcacaagag tcagaccaag gtgccagcac agcctggaaa gagctcagaa 5520 agggggttgg tgcacgtggc tgggcatctt aggaggcttc ctgagggtgg gtaaaggtgg 5580 gaaggccctg gcgctgcatc agatgagcag ggcctggcag ggacaagcct cttctccttt 5640 gggaagccct gcagcctcct agcaagaggc tgattcccca ctctgccccc atctgaatgt 5700 ccttttcatg ttgcacgcag ggaacctcag gaaggaggat tgcctgatgc ctgcctggct 5760 ccatccttga gctctgggca ccacctaggg tgagggagag cctgcagctc tggggctaag 5820 tctgccctgg ggggaaaggg ctccacgctc acacgcacgc gctcgcacac acacactcac 5880 acctggacgc acacggaggc ttgcggaccc atactcacag gcacatgtgg cctggggact 5940 gggggagcag gaaagacccc tccaacattt ggcccttgga aggcaccatt gccaatgagc 6000 ctctttgctg gttcccccga ccccacctgg gggtcccatg ggagcccagc ccagccaggt 6060 gtggggatgg gccaccggcc attcctgttt tccttgtaca gacagattct cactacccac 6120 ccgccatccc cagacacatt ttatttaata acttgtcatt gttaaattat ttattagcgt 6180 ttaccacacc accaccccca ccctgccctc cactctcacc ttccacctct tcccacaaca 6240 gcagaaaatg gaaacaacaa caaaaaaaga tgagacatca gtatatttgt aaataaaccg 6300 acctgtacac tc 6312 <![CDATA[<210> 12]]> <![CDATA[<211> 6234]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 12]]> cccttgcttt tggtgatggt tgtgagtgca gaagttgatt gacagatgca tgccagaaac 60 ccccattctc cttttcaaag acaacatatg atggattgct atctctcagc gcagcaggac 120 acggggacca tgcaagctgt aattggtcag gcatgaactc tcttgggttg tgttaccctg 180 tttgctgttt actgtcaaga tgctgaaaga atgttcttat aatgatccaa gaggaagtgg 240 caaatgagtg ctcttcttca ggatccaatg atagctggac aagtcagtaa gcccttgctg 300 tcagtgcgga gtgaaatgaa tgcggagttg agaggtgagg acaaggctgc tacttcagac 360 agcgagctga atgagcccct gcttgcgcct gtggaatcaa atgacagcga ggacactccc 420 agcaagctct tcggggctag aggaaaccca gcattatcag acccaggcac tcctgaccaa 480 caccaggcca gtcagaccca ccccccattt ccagttgggc cacagccact tctgacggca 540 cagcagttag cttctgctgt ggccggcgtg atgccgggag gccccccagc cctcaaccag 600 ccaatcctca ttcccttcaa catggcggga cagctaggag gccagcaagg actggttctc 660 acactgccaa cagcgaatct caccaacatc caagggctgg tggcagcagc tgcagccgga 720 ggcattatga ctctgccact gcaaaatcta caagctacct catccctgaa ctcccagctc 780 cagcagctcc agctccagct ccagcagcag cagcagcagc agcagcagca gcctcccccg 840 tcaaccaacc agcacccgca accagcccca caggcgccct cgcagtccca gcagcagccg 900 ctgcagccca ccccacccca gcagccacca cccgcctctc agcagccgcc agctcctaca 960 tctcagctgc aacaggcgcc tcagccccag cagcaccaac cccactccca ctcccagaac 1020 cagaaccaac catctccaac ccagcagagc tccagccccc cgcagaaacc tagtcagtct 1080 ccaggacatg gcctgccttc accgctcacg ccacccaatc ctctacagct ggttaataat 1140 ccactagcaa gtcaggctgc agcggctgca gcagccatga gctccatagc aagctcacag 1200 gcctttggca atgccctctc cagtcttcag ggggtcacag gtcaactagt tactaatgca 1260 caaggacaga ttatcgggac cattccactg atgcctaatc cagggccatc gagccaagca 1320 gcaagcggca ctcagggctt gcaagtgcag ccaatcaccc cccagctcct cacaaacgcc 1380 cagggccaga tcatcgccac agtcattggg aaccagatcc tgcccgtgat caacacccag 1440 ggcatcacgc tgtcacccat caagcccggc cagcagctcc accaaccctc ccagacgtca 1500 gtgggtcaag cagcctccca aggcaacctt ctgcacctgg ctcacagcca agcatccatg 1560 tctcaaagtc ccgtccggca ggcttcctct tcttcctcct catcctcctc ttcttcagct 1620 ttgagcgtgg gccagttagt cagcaatcct caaacggcag cgggtgaggt ggatggggtt 1680 aatctggagg agatccgaga atttgccaaa gcttttaaaa tccggcgcct gtcccttggc 1740 ctgacccaga ctcaggtggg acaggctctc agtgctacag agggccccgc gtacagccag 1800 tcggccatct gcagacacac catcctgaga agccactttt tcctaccaca ggaagcccaa 1860 gagaacacta tagctagcag tctgacagcc aaactgaacc ctggcctttt gtatcctgcc 1920 aggtttgaaa agctggacat cacccctaaa agtgcccaga agatcaagcc ggtgcttgag 1980 cggtggatgg ctgaggctga ggcccgccat cgagcaggta tgcagaacct gaccgagttt 2040 atcgggagtg aaccatccaa aaagcgcaag cggcgcacct ccttcacacc ccaggccctt 2100 gagatcctca atgcccactt tgagaagaac acacaccctt ctgggcagga aatgaccgaa 2160 attgctgaga agctgaacta tgaccgagaa gtagttagag tttggttctg caataagagg 2220 caagccctga agaacacaat taaacgctta aaacagcacg agccggccac ggcagtccct 2280 ttggagccct taacagactc tctggaagaa aactcctaaa gagatgccca cccataatca 2340 gaagcaaaat tcacagaaac taaactccac ccttgggact ccacaacaac aacaacaaca 2400 aaatttaatt taatttaaaa atagccccag tcgtcatcac ccttgtaagt aaatgactaa 2460 gaaaactacc aagtggacag aatggtttct acatgtccgt tggttttcca aaaaggaaag 2520 aagaaaattt ttagaaaatt tttaaacaag gaatacacca cactgaaggt gtgtgtggta 2580 ggatagttcc cttcccccac ctgtctcccc caaagccagt tttttaatgg acttaaagca 2640 aaccaaataa ccacgtactt ttttctgtat attatgaaaa tgtgaacaca ttttaaggaa 2700 aaagaaaaaa aaaaactaaa ccaaaaacca acaacgaagg aacaaaaact ttgatctgtt 2760 caaagcgaat acaagcctgc cacctggagg aaggactgca ccccttcagg tactaagtgc 2820 tgattcacta tgaaacctat taaccaaagt cagaaacatg gcattgcaac gcgatcgttc 2880 gtctacgctt ctccgcacgt aaagttgtgt tacgaatttt tacatttgta ctaacagaac 2940 aataggaagc ctgatttctc ccatctttcc catctactgt ctccacccat ggggtgggta 3000 ccattgttga agccattctg tgaggctcac tattgggttt ttttgtgggg gtggtaggga 3060 gggtggtctt ttttctttgt ctttcttttt gacgggaggg catcctggat cgtgtgccaa 3120 agcatttgtt gcttttttct cactatgact tgtgggtttg agaaaagaaa atggagctcg 3180 catttctctc ttttcctcca tttctccatc tccctcgcgc gtggctcctg gggtctgctg 3240 gaaggccaca gaagtgggga gaagcagtgt cttttccact cagatcctag tgaaatgcag 3300 gagagactcc aaaataacta gggctttgct cgatgaactg tcaacactgg cataagctgt 3360 aattgtgctc actgtccaca ccagagcttg ggatttttct cagtctgttg gccacgtaca 3420 tggagagctg accaaaacta attttgtaat ataaacataa gctgcacatt tggttcaata 3480 cttacatcta tgttatgctt ctgtgcaaag caatttctct cagaagtctg atagccaaag 3540 aaatgtctca agatttcagt caaatacaca catgacatgc acacacccat aaacacacac 3600 acaaagaaac aggctaaaaa gaaagtgata gcaactggat cattaaaggc catcgtgtat 3660 cctgttaatc tcatcttttc tgctacttct ttcattccaa tagcgatggc agactttttt 3720 cagggggaat aattactctt cgggatatat aaatggagca gaaaggtggc gggcaaattt 3780 aaacaactgg aattgggggc caggttcttc aggggaaagg aagtttgaag aagctttcac 3840 caaaagaaaa aaatatagaa ggggcttatc taacaatcag aatagcctgc aatatgagaa 3900 ctagaggatt atttccttta aaaaaaataa cttaaaagat ctgtgggcca caataaccta 3960 ataagcaagg acatgttggg atgtgaggac ggctgtgcag gtgagcactt ggcagctgcc 4020 actggtgttt tcacccaggt acaggcagac ggtgttccat taaaggagca ggcaaaagag 4080 agctgtcaat ttgcttgctg ttgaaatgta catatttatg cataatttat aatcatgcta 4140 atgtattatc tagaagtaag ttgtgaaaga aaaaagagaa acccaatctc aagttgccca 4200 actgattaga aatgccatct ccttccccta atacactccc tctccctggg gagtttgagt 4260 ttcttctgtt ggctcctttg ctgtttgtgt aaatgctaca gtataattgt cccctccaat 4320 gattcatgca gcaatcaaga gactaccagc aaggaaactc taaaaggaat cctggaagtg 4380 gaacaagtca ctcgtaaagg tgtttccatt ttaccagtca atgctaactg gaccacagct 4440 aacttgatct tcaatgccaa catcacagag cccctttcgc cacctcaaaa actgcacaaa 4500 catggacaac ccagaaaccc aaaactttat tgattaaaac agattttgga ttctcctagg 4560 acctgctcca aattccatca agaaaagctc cctgcgaaga gaagttaaca agataacata 4620 tgatggatgc taaatattta aatatatgcc ggcagcggtt acataaggcc tgctcagttc 4680 tgagatctat aattgggagg gtctaactag gacagggaaa atataaaata aaagtaatct 4740 tccagagtgg aacaaaaaag aaatatattc atccgacagt cgtaacacca ttcatgtgca 4800 gtgatttttt tatagtttta taattttgta ttgttttata aattatttat aaggtgttgt 4860 aatgcttctt atattaattt tttacagata aattttttgc tacaaggcat aaaaaggtgc 4920 ctgaaccgat tcttaggaat ataaattata ctgtgtaact cataagtctt tgggaccaca 4980 cctaatgctt aattttatga tgacatttct catgtctact tgtaaacaac ttcatatgcc 5040 aatggcgttt aagtgtcttt tatgtttcca tgaactgaag gttaaggttg ccacccacaa 5100 aaaataaaag ccactttggg catatgtgat tgtatttcaa gcttcagtat ttttctcaca 5160 taatttttaa ttattgttat ctgcattttc attacttcat gaaaaaatga cagtggatat 5220 tacattttac acttgtttat agattttctt tctttttcaa ccaagaaaat attttgaaca 5280 attgaaactt ttaattgcat ttgcaaggtt ttggcttctt tatgttgtca tcacacagat 5340 gcacacacac atacacatac aacacaaaag agagaacaaa aaagcaaaag gagctaggaa 5400 aaaaacaaaa caaaacaagt agaggtgtat caaagaactc aagctataac caaaaagaaa 5460 tcgtaaaatg cctttgctcg tttctctacg ctggaccaaa gctcaatatt tgtaggtata 5520 tgcacattgt atagatatgg ctaaatgttg ctgacaatct cgcaatacta aactgttcct 5580 attttaagaa aaaaaaaaga aatacaaact gttcatcaat gttttacctc agcactctac 5640 ttgtacccag ttaatgacca agcttaaaaa aaaattgaga taaaggaaat tgattttcat 5700 ttcaatgttt gactgtaaaa tctgtttgga taacattttg taatgagctt tttgtcatgt 5760 gatttgcttg tcttcaactt gaaattatgt gaggcacatt tgtttatttg ttgttaagaa 5820 agtgattttt tttttttttt gtcctatgtg ctgtgatcta gactggtcac cggggtcact 5880 tatgaggcac cacaaagaga tctgcttctc cgtgcccgga gcaggcagca ggagggaggg 5940 caggaaacag gactgggttg ctttggaaaa atcatcatga caagaagttg acatgataga 6000 cttgtgacca agaagccaaa ctgaatattt aaaagctcct tacttgctct gacattgaaa 6060 ccaaagctga ttttatctgc acaggttgct taatatttaa aaaaaaaaaa aactgtactt 6120 aatctagagc aatatctgta tggtcagtaa agctgcactt tgtgtatttc ttaacagctt 6180 cagatctgtc acttttaatt tgtaccataa aaaataaata attgtttgac atga 6234 <![CDATA[<210> 13]]> <![CDATA[<211> 6126]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 13]]> cccttgcttt tggtgatggt tgtgagtgca gaagttgatt gacagatgca tgccagaaac 60 ccccattctc cttttcaaag acaacatatg atggattgct atctctcagc gcagcaggac 120 acggggacca tgcaagctgt aattggtcag gcatgaactc tcttgggttg tgttaccctg 180 tttgctgttt actgtcaaga tgctgaaaga atgttcttat aatgatccaa gaggaagtgg 240 caaatgagtg ctcttcttca ggatccaatg atagctggac aagtcagtaa gcccttgctg 300 tcagtgcgga gtgaaatgaa tgcggagttg agaggtgagg acaaggctgc tacttcagac 360 agcgagctga atgagcccct gcttgcgcct gtggaatcaa atgacagcga ggacactccc 420 agcaagctct tcggggctag aggaaaccca gcattatcag acccaggcac tcctgaccaa 480 caccaggcca gtcagaccca ccccccattt ccagttgggc cacagccact tctgacggca 540 cagcagttag cttctgctgt ggccggcgtg atgccgggag gccccccagc cctcaaccag 600 ccaatcctca ttcccttcaa catggcggga cagctaggag gccagcaagg actggttctc 660 acactgccaa cagcgaatct caccaacatc caagggctgg tggcagcagc tgcagccgga 720 ggcattatga ctctgccact gcaaaatcta caagctacct catccctgaa ctcccagctc 780 cagcagctcc agctccagct ccagcagcag cagcagcagc agcagcagca gcctcccccg 840 tcaaccaacc agcacccgca accagcccca caggcgccct cgcagtccca gcagcagccg 900 ctgcagccca ccccacccca gcagccacca cccgcctctc agcagccgcc agctcctaca 960 tctcagctgc aacaggcgcc tcagccccag cagcaccaac cccactccca ctcccagaac 1020 cagaaccaac catctccaac ccagcagagc tccagccccc cgcagaaacc tagtcagtct 1080 ccaggacatg gcctgccttc accgctcacg ccacccaatc ctctacagct ggttaataat 1140 ccactagcaa gtcaggctgc agcggctgca gcagccatga gctccatagc aagctcacag 1200 gcctttggca atgccctctc cagtcttcag ggggtcacag gtcaactagt tactaatgca 1260 caaggacaga ttatcgggac cattccactg atgcctaatc cagggccatc gagccaagca 1320 gcaagcggca ctcagggctt gcaagtgcag ccaatcaccc cccagctcct cacaaacgcc 1380 cagggccaga tcatcgccac agtcattggg aaccagatcc tgcccgtgat caacacccag 1440 ggcatcacgc tgtcacccat caagcccggc cagcagctcc accaaccctc ccagacgtca 1500 gtgggtcaag cagcctccca aggcaacctt ctgcacctgg ctcacagcca agcatccatg 1560 tctcaaagtc ccgtccggca ggcttcctct tcttcctcct catcctcctc ttcttcagct 1620 ttgagcgtgg gccagttagt cagcaatcct caaacggcag cgggtgaggt ggatggggtt 1680 aatctggagg agatccgaga atttgccaaa gcttttaaaa tccggcgcct gtcccttggc 1740 ctgacccaga ctcaggtggg acaggctctc agtgctacag agggccccgc gtacagccag 1800 tcggccatct gcaggtttga aaagctggac atcaccccta aaagtgccca gaagatcaag 1860 ccggtgcttg agcggtggat ggctgaggct gaggcccgcc atcgagcagg tatgcagaac 1920 ctgaccgagt ttatcgggag tgaaccatcc aaaaagcgca agcggcgcac ctccttcaca 1980 ccccaggccc ttgagatcct caatgcccac tttgagaaga acacacaccc ttctgggcag 2040 gaaatgaccg aaattgctga gaagctgaac tatgaccgag aagtagttag agtttggttc 2100 tgcaataaga ggcaagccct gaagaacaca attaaacgct taaaacagca cgagccggcc 2160 acggcagtcc ctttggagcc cttaacagac tctctggaag aaaactccta aagagatgcc 2220 cacccataat cagaagcaaa attcacagaa actaaactcc acccttggga ctccacaaca 2280 acaacaacaa caaaatttaa tttaatttaa aaatagcccc agtcgtcatc acccttgtaa 2340 gtaaatgact aagaaaacta ccaagtggac agaatggttt ctacatgtcc gttggttttc 2400 caaaaaggaa agaagaaaat ttttagaaaa tttttaaaca aggaatacac cacactgaag 2460 gtgtgtgtgg taggatagtt cccttccccc acctgtctcc cccaaagcca gttttttaat 2520 ggacttaaag caaaccaaat aaccacgtac ttttttctgt atattatgaa aatgtgaaca 2580 cattttaagg aaaaagaaaa aaaaaaacta aaccaaaaac caacaacgaa ggaacaaaaa 2640 ctttgatctg ttcaaagcga atacaagcct gccacctgga ggaaggactg caccccttca 2700 ggtactaagt gctgattcac tatgaaacct attaaccaaa gtcagaaaca tggcattgca 2760 acgcgatcgt tcgtctacgc ttctccgcac gtaaagttgt gttacgaatt tttacatttg 2820 tactaacaga acaataggaa gcctgatttc tcccatcttt cccatctact gtctccaccc 2880 atggggtggg taccattgtt gaagccattc tgtgaggctc actattgggt ttttttgtgg 2940 gggtggtagg gagggtggtc ttttttcttt gtctttcttt ttgacgggag ggcatcctgg 3000 atcgtgtgcc aaagcatttg ttgctttttt ctcactatga cttgtgggtt tgagaaaaga 3060 aaatggagct cgcatttctc tcttttcctc catttctcca tctccctcgc gcgtggctcc 3120 tggggtctgc tggaaggcca cagaagtggg gagaagcagt gtcttttcca ctcagatcct 3180 agtgaaatgc aggagagact ccaaaataac tagggctttg ctcgatgaac tgtcaacact 3240 ggcataagct gtaattgtgc tcactgtcca caccagagct tgggattttt ctcagtctgt 3300 tggccacgta catggagagc tgaccaaaac taattttgta atataaacat aagctgcaca 3360 tttggttcaa tacttacatc tatgttatgc ttctgtgcaa agcaatttct ctcagaagtc 3420 tgatagccaa agaaatgtct caagatttca gtcaaataca cacatgacat gcacacaccc 3480 ataaacacac acacaaagaa acaggctaaa aagaaagtga tagcaactgg atcattaaag 3540 gccatcgtgt atcctgttaa tctcatcttt tctgctactt ctttcattcc aatagcgatg 3600 gcagactttt ttcaggggga ataattactc ttcgggatat ataaatggag cagaaaggtg 3660 gcgggcaaat ttaaacaact ggaattgggg gccaggttct tcaggggaaa ggaagtttga 3720 agaagctttc accaaaagaa aaaaatatag aaggggctta tctaacaatc agaatagcct 3780 gcaatatgag aactagagga ttatttcctt taaaaaaaat aacttaaaag atctgtgggc 3840 cacaataacc taataagcaa ggacatgttg ggatgtgagg acggctgtgc aggtgagcac 3900 ttggcagctg ccactggtgt tttcacccag gtacaggcag acggtgttcc attaaaggag 3960 caggcaaaag agagctgtca atttgcttgc tgttgaaatg tacatattta tgcataattt 4020 ataatcatgc taatgtatta tctagaagta agttgtgaaa gaaaaaagag aaacccaatc 4080 tcaagttgcc caactgatta gaaatgccat ctccttcccc taatacactc cctctccctg 4140 gggagtttga gtttcttctg ttggctcctt tgctgtttgt gtaaatgcta cagtataatt 4200 gtcccctcca atgattcatg cagcaatcaa gagactacca gcaaggaaac tctaaaagga 4260 atcctggaag tggaacaagt cactcgtaaa ggtgtttcca ttttaccagt caatgctaac 4320 tggaccacag ctaacttgat cttcaatgcc aacatcacag agcccctttc gccacctcaa 4380 aaactgcaca aacatggaca acccagaaac ccaaaacttt attgattaaa acagattttg 4440 gattctccta ggacctgctc caaattccat caagaaaagc tccctgcgaa gagaagttaa 4500 caagataaca tatgatggat gctaaatatt taaatatatg ccggcagcgg ttacataagg 4560 cctgctcagt tctgagatct ataattggga gggtctaact aggacaggga aaatataaaa 4620 taaaagtaat cttccagagt ggaacaaaaa agaaatatat tcatccgaca gtcgtaacac 4680 cattcatgtg cagtgatttt tttatagttt tataattttg tattgtttta taaattattt 4740 ataaggtgtt gtaatgcttc ttatattaat tttttacaga taaatttttt gctacaaggc 4800 ataaaaaggt gcctgaaccg attcttagga atataaatta tactgtgtaa ctcataagtc 4860 tttgggacca cacctaatgc ttaattttat gatgacattt ctcatgtcta cttgtaaaca 4920 acttcatatg ccaatggcgt ttaagtgtct tttatgtttc catgaactga aggttaaggt 4980 tgccacccac aaaaaataaa agccactttg ggcatatgtg attgtatttc aagcttcagt 5040 atttttctca cataattttt aattattgtt atctgcattt tcattacttc atgaaaaaat 5100 gacagtggat attacatttt acacttgttt atagattttc tttctttttc aaccaagaaa 5160 atattttgaa caattgaaac ttttaattgc atttgcaagg ttttggcttc tttatgttgt 5220 catcacacag atgcacacac acatacacat acaacacaaa agagagaaca aaaaagcaaa 5280 aggagctagg aaaaaaacaa aacaaaacaa gtagaggtgt atcaaagaac tcaagctata 5340 accaaaaaga aatcgtaaaa tgcctttgct cgtttctcta cgctggacca aagctcaata 5400 tttgtaggta tatgcacatt gtatagatat ggctaaatgt tgctgacaat ctcgcaatac 5460 taaactgttc ctattttaag aaaaaaaaaa gaaatacaaa ctgttcatca atgttttacc 5520 tcagcactct acttgtaccc agttaatgac caagcttaaa aaaaaattga gataaaggaa 5580 attgattttc atttcaatgt ttgactgtaa aatctgtttg gataacattt tgtaatgagc 5640 tttttgtcat gtgatttgct tgtcttcaac ttgaaattat gtgaggcaca tttgtttatt 5700 tgttgttaag aaagtgattt tttttttttt ttgtcctatg tgctgtgatc tagactggtc 5760 accggggtca cttatgaggc accacaaaga gatctgcttc tccgtgcccg gagcaggcag 5820 caggagggag ggcaggaaac aggactgggt tgctttggaa aaatcatcat gacaagaagt 5880 tgacatgata gacttgtgac caagaagcca aactgaatat ttaaaagctc cttacttgct 5940 ctgacattga aaccaaagct gattttatct gcacaggttg cttaatattt aaaaaaaaaa 6000 aaaactgtac ttaatctaga gcaatatctg tatggtcagt aaagctgcac tttgtgtatt 6060 tcttaacagc ttcagatctg tcacttttaa tttgtaccat aaaaaataaa taattgtttg 6120 acatga 6126 <![CDATA[<210> 14]]> <![CDATA[<211> 1419]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 14]]> catttctact ttgcccgccc acagatgtag ttttctctgc gcgtgtgcgt tttccctcct 60 ccccgccctc agggtccacg gccaccatgg cgtattaggg gcagcagtgc ctgcggcagc 120 attggccttt gcagcggcgg cagcagcacc aggctctgca gcggcaaccc ccagcggctt 180 aagccatggc gcttctcacg gcattcagca gcagcgttgc tgtaaccgac aaagacacct 240 tcgaattaag cacattcctc gattccagca aagcaccgca acatgaccga aatgagcttc 300 ctgagcagcg aggtgttggt gggggacttg atgtccccct tcgaccagtc gggtttgggg 360 gctgaagaaa gcctaggtct cttagatgat tacctggagg tggccaagca cttcaaacct 420 catgggttct ccagcgacaa ggctaaggcg ggctcctccg aatggctggc tgtggatggg 480 ttggtcagtc cctccaacaa cagcaaggag gatgccttct ccgggacaga ttggatgttg 540 gagaaaatgg atttgaagga gttcgacttg gatgccctgt tgggtataga tgacctggaa 600 accatgccag atgaccttct gaccacgttg gatgacactt gtgatctctt tgccccccta 660 gtccaggaga ctaataagca gcccccccag acggtgaacc caattggcca tctcccagaa 720 agtttaacaa aacccgacca ggttgccccc ttcaccttct tacaacctct tcccctttcc 780 ccaggggtcc tgtcctccac tccagatcat tcctttagtt tagagctggg cagtgaagtg 840 gatatcactg aaggagatag gaagccagac tacactgctt acgttgccat gatccctcag 900 tgcataaagg aggaagacac cccttcagat aatgatagtg gcatctgtat gagcccagag 960 tcctatctgg ggtctcctca gcacagcccc tctaccaggg gctctccaaa taggagcctc 1020 ccatctccag gtgttctctg tgggtctgcc cgtcccaaac cttacgatcc tcctggagag 1080 aagatggtag cagcaaaagt aaagggtgag aaactggata agaagctgaa aaaaatggag 1140 caaaacaaga cagcagccac taggtaccgc cagaagaaga gggcggagca ggaggctctt 1200 actggtgagt gcaaagagct ggaaaagaag aacgaggctc taaaagagag ggcggattcc 1260 ctggccaagg agatccagta cctgaaagat ttgatagaag aggtccgcaa ggcaaggggg 1320 aagaaaaggg tcccctagtt gaggatagtc aggagcgtca atgtgcttgt acatagagtg 1380 ctgtagctgt gtgttccaat aaattatttt gtagggaaa 1419 <![CDATA[<210> 15]]> <![CDATA[<211> 4881]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 15]]> gaactgggcc gggcggccgt gcgggagcca tggcggcctc ggaggcggcg gcggcggcgg 60 ggtccgcggc tctggcggcg ggtgcccggg ccgtcccggc ggccacgaca ggagccgccg 120 ccgccgcctc gggcccgtgg gtgcccccgg gaccccgact gaggggcagc cggccgcggc 180 ccgcgggggc gacgcagcag cccgctgtcc ccgcgccgcc ggcgggggag ctgatccagc 240 cgtcggtgag cgagctgtcc cgggccgtgc ggaccaacat cctgtgcacc gtgcgcggct 300 gcggcaagat cctgcccaac agccccgcgc tcaacatgca cctagtcaag agccaccgcc 360 tgcaggatgg catagtcaat ccaacaataa gaaaagattt gaaaactgga ccgaaattct 420 actgctgtcc aattgaaggc tgccccagag gccctgagag accgttttct cagttttctc 480 tcgtaaaaca gcactttatg aaaatgcatg ctgagaagaa gcacaaatgt agtaagtgca 540 gcaattcgta cggtacagaa tgggacctga aaagacatgc agaggactgt ggcaagacct 600 tccggtgcac atgcggctgt ccctacgcca gtagaacagc actgcagtct cacatctacc 660 gaactgggca cgagatacct gcagaacaca gggacccacc tagtaagaaa aggaaaatgg 720 aaaactgtgc acaaaaccag aagttatcca acaagaccat tgaatcattg aacaaccaac 780 caatccctag accagacact caagaactag aagcttcaga aataaagcta gaaccatctt 840 ttgaagactc ttgtggctct aacactgaca agcagactct tacaacacca ccgagatatc 900 ctcagaagtt gcttttacca aagcccaaag tggctttggt taaactaccc gtgatgcagt 960 tttctgtcat gcctgtcttt gtgcctacag ccgactcctc agcccagcct gtggtgttag 1020 gtgttgatca gggctctgcc acaggggctg tgcacttaat gcccttgtca gtaggaaccc 1080 tgatcctcgg cctagattca gaggcttgct ctcttaagga gagcctacct cttttcaaaa 1140 ttgctaatcc tattgctggt gagccaataa gtactggtgt tcaagtgaac tttggtaaaa 1200 gtccatctaa tcctttacaa gaactaggga acacgtgtca aaagaatagc atttcttcaa 1260 tcaacgtgca gacagatctg tcttatgcct cacaaaactt tataccttct gcacagtggg 1320 ccactgctga ttcctctgtg tcgtcttgtt ctcaaactga tttgtcgttt gattctcaag 1380 tgtctcttcc cattagtgtt cacactcaga catttttgcc cagctctaag gtaacttcat 1440 ctatagctgc tcagactgat gcatttatgg acacctgttt ccagtcaggt ggggtctcca 1500 gagaaactca aaccagtggg atagaaagtc caacggatga ccatgtacag atggaccaag 1560 ctggaatgtg cggagacatt tttgagagtg ttcattcatc atataatgtt gctacaggta 1620 acattataag caacagttta gtagcagaga cagtaactca tagtttgtta cctcagaatg 1680 agcctaagac tttaaatcaa gatattgaga aatctgcacc aattataaat ttcagtgcac 1740 agaatagtat gcttccttca cagaacatga cagataatca gacccaaacc atagatttat 1800 taagtgattt ggaaaacatc ttgtcaagta atctgcctgc tcagacattg gatcatcgta 1860 gtcttttgtc tgacacaaat cctggacctg acacccagct cccatctggc ccagcccaga 1920 accccggaat cgattttgat atcgaagagt tcttttcggc ctcaaatatc cagactcaaa 1980 ctgaagagag tgaacttagc accatgacca ccgagccagt cttggagtca ctggacatag 2040 agactcaaac ggacttctta ctcgcagata cctctgctca gtcctatggg tgtaggggaa 2100 attctaactt cttaggcctt gagatgtttg acacacagac acagacagac ttaaactttt 2160 tcttagacag tagccctcat ctgcctctgg gaagtattct gaaacactcc agcttttccg 2220 tgagtactga ttcatctgac acagagaccc aaactgaagg agtctccact gctaaaaata 2280 tacctgctct agaaagcaaa gttcagttga acagtacaga aacacagacc atgagttctg 2340 ggtttgaaac cctggggagc ttgttcttca ccagcaacga aactcagaca gcaatggatg 2400 actttcttct ggctgatctg gcctggaaca cgatggagtc tcagttcagc tctgtagaaa 2460 cccagacttc tgcggaacca cacacagtct ccaacttcta aaactaacgg tggagtccat 2520 gtgtgaaatg gcatctacca tttcctctgg attaaaacta cggactgggg acaacagtat 2580 taattcgatt gaatgtggct gatgatgcag ttgcttagct tctttgtgtt tctttgcctt 2640 ttgtacttgt aaacagaaat ttgcgtataa atgtgagtgt attataaagt ttgagatgtt 2700 gatctaaatt gtttttgtgt tgcctacatt tgccttttca cagctagtct tttcatgtta 2760 aaaaaaaaaa tgtatttcat atctataaaa cctatatagc catttagctg aagcccagct 2820 taccaggttc aagggtacaa acttctcaaa tcttcaaaac attttagtca aagtgtaata 2880 tacttaaact gcacctaaaa tatctttggc actgcttgtt agaaattcct gattcctgtt 2940 actaatcact aaagaaaccg gatgctgcca ccgtaggatt taagcagtag tgcttccatg 3000 ctcttaagac tcctgctgcc tggaccttcg tcagctttga cacctctttt ctgatttaaa 3060 gacaccaagg aaaactacaa ctgtctttag ctttgaagca gttttcatgt aatcattgcc 3120 acctcttcgc tacatgaact actattgata ccagcataca agtgtacagc actttacaca 3180 caagaggttt attgatgtaa aattatcggc tagggaagca gcagcgggcc aggtgtggtg 3240 gcttacccct gtaatcccag cactttggga ggccaaagca ggacgatcac ttgagcccag 3300 gagttcaaca ccagcttggg caacgtaaga agaccgtgtc tctggaattt tttttttttt 3360 ttaattagcc aggcacagtg gcatgcgcct gtgatcccag ctacttggaa ggctgaggtg 3420 agaggatcac tcgaggagat tggggctgcc atgagccatg gtcttggcac tgtactccaa 3480 cctgggtaac agggcaagac cctatctcaa aaaaaaaaaa agtcgccagc aacaagcacg 3540 tagtgtagtg ttcctgctaa atgagcgtag gttatccaaa ccttgggaac agggagttat 3600 ggaaacatgc ctatgacttc atcttggggt gtgtcctatg aagatccttt ctggtctcca 3660 cagtaggcca gagttggggg ctctggagct gtttccccaa gtgcatccac aagctggatc 3720 tgagttttgt cactctaaaa ttaaacaaga aaaaaagtgg gaaaagggca tcccccatta 3780 ggtttcaata ctttgcactt ctactaagct tgatagggca ggagtgcaat ctacaattat 3840 tttaaagtga atttccttcc attcaccatt ctttatcttt tctttgaata agaaaaagta 3900 tctagcaagg atattacttg tgccttgagg ctagcaatta taggatagat tcatctaaaa 3960 tatggtattc tgcattttgg ttttttttct taagtgaata ataccagtct tcaaagaaaa 4020 caaggtgaag acctattgct tcaataatca agaatgcttt gtgtgttttg aggtaggagc 4080 atgatcaagt atgctttggg gattttctgt atttaggaga tcctggattc ttaattgttg 4140 gctaagttcc agtcaagtag gaatcagtgc agcctgtaag ttctccacat tgacacacac 4200 acacacacac acacacacac acgacatgct cctttctgtg gcacatgcct gtattactga 4260 aagctaaatc ctcaaaacct agtaagggga ctaatgattc attaaagtaa attgatggtt 4320 ttgctactaa ttcctatccc atacatttga cacaaaagaa gtgttggtaa tggataaata 4380 acatatcccg ggcagatgag ctcaacctag taggtaagag tttggtttgg tcacagttgc 4440 ctatgagtgt gggtttcaaa agaaacataa agccttaact tagaatttca ttatgtttta 4500 gaatcatcac tgccttaata ttcaagcatc tatttaagtc ctaataaagg agaaatgcat 4560 gtttatggct tttttgtaaa tataaatgca gtgatctatg gcttaaaaaa tttgtttctg 4620 tgacaatgtt tgtaaatcta gccaatagag tcatttacag aagaaaaatg agcatgtaat 4680 aatacaagaa ctgtttcccc ctcaaaacct gaacctgaat tatttgtaaa aactgaaatt 4740 taatgattaa agagaagcca gaattgtacc cttttttgtg aattcttgaa cgtactcata 4800 aatatgactt attgtattgc cttaagtttt cactcattgt cttttgaaag ccatatgata 4860 aaatgatttt atttaataat a 4881 <![CDATA[<210> 16]]> <![CDATA[<211> 3152]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 16]]> attcacttgg ctcgcacggc gcagacagac cgcgcaggga gcacacaccg ccagtctgtg 60 cgctgagtcg gagccagagg ccgcggggac accgggccat gcacgccccc aactgaagct 120 gcatctcaaa gccgaagatt ccagcagccc aggggatttc aaagagctca gactcagagg 180 aacatctgcg gagagacccc cgaagccctc tccagggcag tcctcatcca gacgctccgc 240 tagtgcagac aggagcgcgc agtggccccg gctcgccgcg ccatggagcg gatccccagc 300 gcgcaaccac cccccgcctg cctgcccaaa gcaccgggac tggagcacgg agacctacca 360 gggatgtacc ctgcccacat gtaccaagtg tacaagtcaa gacggggaat aaagcggagc 420 gaggacagca aggagaccta caaattgccg caccggctca tcgagaaaaa gagacgtgac 480 cggattaacg agtgcatcgc ccagctgaag gatctcctac ccgaacatct caaacttaca 540 actttgggtc acttggaaaa agcagtggtt cttgaactta ccttgaagca tgtgaaagca 600 ctaacaaacc taattgatca gcagcagcag aaaatcattg ccctgcagag tggtttacaa 660 gctggtgagc tgtcagggag aaatgtcgaa acaggtcaag agatgttctg ctcaggtttc 720 cagacatgtg cccgggaggt gcttcagtat ctggccaagc acgagaacac tcgggacctg 780 aagtcttcgc agcttgtcac ccacctccac cgggtggtct cggagctgct gcagggtggt 840 acctccagga agccatcaga cccagctccc aaagtgatgg acttcaagga aaaacccagc 900 tctccggcca aaggttcgga aggtcctggg aaaaactgcg tgccagtcat ccagcggact 960 ttcgctcact cgagtgggga gcagagcggc agcgacacgg acacagacag tggctatgga 1020 ggagaatcgg agaagggcga cttgcgcagt gagcagccgt gcttcaaaag tgaccacgga 1080 cgcaggttca cgatgggaga aaggatcggc gcaattaagc aagagtccga agaacccccc 1140 acaaaaaaga accggatgca gctttcggat gatgaaggcc atttcactag cagtgacctg 1200 atcagctccc cgttcctggg cccacaccca caccagcctc ctttctgcct gcccttctac 1260 ctgatcccac cttcagcgac tgcctacctg cccatgctgg agaagtgctg gtatcccacc 1320 tcagtgccag tgctataccc aggcctcaac gcctctgccg cagccctctc tagcttcatg 1380 aacccagaca agatctcggc tcccttgctc atgccccaga gactcccttc tcccttgcca 1440 gctcatccgt ccgtcgactc ttctgtcttg ctccaagctc tgaagccaat ccccccttta 1500 aacttagaaa ccaaagacta aactctctag gggatcctgc tgctttgctt tccttcctcg 1560 ctacttccta aaaagcaaca aaaaagtttt tgtgaatgct gcaagattgt tgcattgtgt 1620 atactgagat aatctgaggc atggagagca gattcagggt gtgtgtgtgt gtgtgtgtgt 1680 gtgtatgtgc gtgtgcgtgc acatgtgtgc ctgcgtgttg gtataggact ttaaagctcc 1740 ttttggcata gggaagtcac gaaggattgc ttgacatcag gagacttggg ggggattgta 1800 gcagacgtct gggcttttcc ccacccagag aatagccccc ttcgatacac atcagctgga 1860 ttttcaaaag cttcaaagtc ttggtctgtg agtcactctt cagtttggga gctgggtctg 1920 tggctttgat cagaaggtac tttcaaaaga gggctttcca gggctcagct cccaaccagc 1980 tgttaggacc ccaccctttt gcctttattg tcgacgtgac tcaccagacg tcggggagag 2040 agagcagtca gaccgagctt tctgctaaca tggggaggta gcaggcactg gcatagcacg 2100 gtagtggttt ggggaggttt ccgcaggtct gctccccacc cctgcctcgg aagaataaag 2160 agaatgtagt tccctactca ggctttcgta gtgattagct tactaaggaa ctgaaaatgg 2220 gccccttgta caagctgagc tgccccggag ggagggagga gttccctggg cttctggcac 2280 ctgtttctag gcctaaccat tagtacttac tgtgcaggga accaaaccaa ggtctgagaa 2340 atgcggacac cccgagcgag caccccaaag tgcacaaagc tgagtaaaaa gctgccccct 2400 tcaaacagaa ctagactcag ttttcaattc catcctaaaa ctccttttaa ccaagcttag 2460 cttctcaaag gcctaaccaa gccttggcac cgccagatcc tttctgtagg ctaattcctc 2520 ttgcccaacg gcatatggag tgtccttatt gctaaaaagg attccgtctc cttcaaagaa 2580 gttttatttt tggtccagag tacttgtttt cccgatgtgt ccagccagct ccgcagcagc 2640 ttttcaaaat gcactatgcc tgattgctga tcgtgtttta actttttctt ttcctgtttt 2700 tattttggta ttaagtcgtt gcctttattt gtaaagctgt tataaatata tattatataa 2760 atatattaaa aaggaaaatg tttcagatgt ttatttgtat aattacttga ttcacacagt 2820 gagaaaaaat gaatgtattc ctgtttttga agagaagaat aatttttttt ttctctaggg 2880 agaggtacag tgtttatatt ttggagcctt cctgaaggtg taaaattgta aatattttta 2940 tctatgagta aatgttaagt agttgtttta aaatacttaa taaaataatt cttttcctgt 3000 ggaagagaaa gatggtctcc tgagtttttt aaaatagctc acttggtgtg atatggctga 3060 ctcccatgtc cttctttctt ggctgaagca aaccagttaa tctcagtgta atttcattca 3120 gcttttcatg tgctttgtat tcaatcagaa ta 3152 <![CDATA[<210> 17]]> <![CDATA[<211> 1252]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 17]]> aggtgacagc ctcgcttgga cgcagagccc ggcccgacgc cgccatgagc gccgcgctct 60 tcagcctgga cggcccggcg cgcggcgcgc cctggcctgc ggagcctgcg cccttctacg 120 aaccgggccg ggcgggcaag ccgggccgcg gggccgagcc aggggcccta ggcgagccag 180 gcgccgccgc ccccgccatg tacgacgacg agagcgccat cgacttcagc gcctacatcg 240 actccatggc cgccgtgccc accctggagc tgtgccacga cgagctcttc gccgacctct 300 tcaacagcaa tcacaaggcg ggcggcgcgg ggcccctgga gcttcttccc ggcggccccg 360 cgcgcccctt gggcccgggc cctgccgctc cccgcctgct caagcgcgag cccgactggg 420 gcgacggcga cgcgcccggc tcgctgttgc ccgcgcaggt ggccgcgtgc gcacagaccg 480 tggtgagctt ggcggccgca gggcagccca ccccgcccac gtcgccggag ccgccgcgca 540 gcagccccag gcagaccccc gcgcccggcc ccgcccggga gaagagcgcc ggcaagaggg 600 gcccggaccg cggcagcccc gagtaccggc agcggcgcga gcgcaacaac atcgccgtgc 660 gcaagagccg cgacaaggcc aagcggcgca accaggagat gcagcagaag ttggtggagc 720 tgtcggctga gaacgagaag ctgcaccagc gcgtggagca gctcacgcgg gacctggccg 780 gcctccggca gttcttcaag cagctgccca gcccgccctt cctgccggcc gccgggacag 840 cagactgccg gtaacgcgcg gccggggcgg gagagactca gcaacgaccc atacctcaga 900 cccgacggcc cggagcggag cgcgccctgc cctggcgcag ccagagccgc cgggtgcccg 960 ctgcagtttc ttgggacata ggagcgcaaa gaagctacag cctggactta ccaccactaa 1020 actgcgagag aagctaaacg tgtttatttt cccttaaatt atttttgtaa tggtagcttt 1080 ttctacatct tactcctgtt gatgcagcta aggtacattt gtaaaaagaa aaaaaaccag 1140 acttttcaga caaacccttt gtattgtaga taagaggaaa agactgagca tgctcacttt 1200 tttatattaa tttttacagt atttgtaaga ataaagcagc atttgaaatc gc 1252 <![CDATA[<210> 18]]> <![CDATA[<211> 3164]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 18]]> agtctcccgc cgccgccgcc gctgccggac gcgcagagcg aggggcggct ggaccgacgg 60 ctgccgggcc gagcgcacag agtcgcggcg cagggggcgt ccccggccgg gacgcgggtc 120 gcgtcgttgt cctccgcgag cgtccggatt gcaggctgtc tgtccccaga ccccagagca 180 cgtccggcac caccatgact gggctgttga agaggaaatt tgaccagctg gatgaggaca 240 actcctcggt ctcctcctcc tcctcttcct ctgggtgcca gtctcgctcc tgctccccaa 300 gctcttctgt ctcccgtgcc tgggactcag aggaggaagg cccctgggat cagatgcccc 360 tgcctgaccg tgacttctgc ggccccagaa gtttcacccc cctgtctatc ctgaagcggg 420 ctcgccggga gcgcccaggc cgtgtagcct ttgatgggat caccgtcttc tacttccccc 480 gctgccaggg cttcaccagt gtgcccagcc gtggtggctg tactctgggt atggcccttc 540 gccacagtgc ttgccgtcgc ttctctttgg ctgagtttgc gcaggagcaa gcccgtgcac 600 ggcacgagaa gctccgccag cgcttgaaag aggagaagtt ggagatgctg cagtggaagc 660 tttcggcagc tggggtaccc caggcagagg cagggctgcc acctgtggtg gatgccattg 720 atgacgcctc tgtggaggag gacttggcag tcgctgtggc aggtggccgg ttggaagaag 780 tgagcttcct acagccctac ccagcccggc gacgtcgagc tctgctgagg gcttcaggtg 840 tgcgaaggat cgatcgggag gagaagcggg agctgcaggc actgcgccaa tcccgggagg 900 attgtggctg tcactgcgat aggatctgcg accctgagac ctgcagctgc agcctggcag 960 gcatcaagtg ccagatggac cacacagcat tcccctgtgg ctgctgcagg gagggctgtg 1020 agaaccccat gggccgtgtg gaatttaatc aggcaagagt tcagacccat ttcatccaca 1080 cactcacccg cctgcagttg gaacaggagg ctgagagctt tagggagctg gaggcccctg 1140 cccagggcag cccacccagc cctggtgagg aggccctggt ccctactttc ccactggcca 1200 agccccccat gaacaatgag ctgggagaca acagctgcag cagcgacatg actgattctt 1260 ctacagcatc ttcatcagca tcgggcacta gtgaggctcc tgactgcccc acccacccag 1320 gcctgcctgg ccctggcttc cagcctggcg ttgatgatga cagcctggca cgcatcttga 1380 gtttcagtga ctctgacttc ggtggggagg aggaggaaga ggaggaaggg agcgtgggga 1440 acctggacaa cctcagctgc ttccatccag ctgacatctt tggtactagt gaccctggtg 1500 gcctggccag ctggacccac agctattctg gctgtagctt cacatcaggc gtcctggatg 1560 agaatgccaa cctggatgcc agctgcttcc taaatggtgg ccttgaaggg tcaagggaag 1620 gcagccttcc tggcacctca gtgccaccca gcatggacgc tggccggagt agctcagtgg 1680 atctcagctt gtcttcttgt gactcctttg agttactcca ggctctgcca gattatagtc 1740 tggggcctca ctacacatca cagaaggtgt ctgacagcct ggacaacatc gaggcacctc 1800 acttccccct gcctggcctg tctccacctg gggatgccag cagttgcttc ctggagtccc 1860 tcatgggctt ctccgagcca gccgccgaag ccctagatcc ctttattgac agccagtttg 1920 aggacactgt cccagcatct ctaatggagc ctgtgccggt gtgaggacca ggatgtcttt 1980 tcccagcccc aagagacctg ttgctgcttt cttgtaatta tggggctccc cagagtctgc 2040 gtaacagtct cccactggct ggctcaccca caggtgccat gtgcacactc ctggttttca 2100 aacaattctc tggatttatt tatttgtttt aacttttctg tgctgaagag aggactgggg 2160 ggagggggct tcccctttca gctgcccggc cccccacacc cacagcttgc tcttctatct 2220 ccacaacgtg agcctggaag aggagaaaat gtggctcctc tggagcttgg cagaccactt 2280 ttcggtcttt gcgtgatgtt ccttagccca aagacggtga gacagggctg aaatcaggtg 2340 gcttctgcca ccctgagccc tagacccatg ggtggctaaa tccactggac tgtgaagact 2400 ataatttatt tccataattt atttggagat tgaggaggct ttggttgcac ttctttggct 2460 ggtgggtaat gccaggggtg gggtgggcac aggccctcaa gagccccttt tgccttgtag 2520 tcctacacct tgccctgcct gggctttggt gcagactagg tgtggatttg agctctgtga 2580 tctatgtctg ctgcctggct cctagatggc tctgtgggca ggtgctggcc aaggacatca 2640 tctaggcagg gggagagcct gggctgaaca gctgtgacca aaactccctt ctgccccacc 2700 ctgccccctc cacttcctgc cctctgttcc atcttccccc ttcccaaagg ccacagcctt 2760 tattccaggc ccagggatgt aggaggggga aggaggaaac aggaagccca gagagggcaa 2820 agggcctacc tcggggcgcg aaccatgccc cagactatta tctcagggct ttctgggcac 2880 tgcacttcag cgtggcccac ctgcccatgc cctgaggcca gttggcgagg ggtggctcct 2940 gagggttttt ataccctttg tttgctaatg tttaattttg catcataatt tctacattgt 3000 ccctgagtgt cagaactata atttattcca tttctctctg tgtctgtgcc aagaaacgca 3060 ggctctgggc ctgccccttg cccaggaggc cttgccagcc tgtgtgcttg tgggaacacc 3120 ttgtacctga gcttacaggt accaataaag aggctttatt ttta 3164 <![CDATA[<210> 19]]> <![CDATA[<211> 822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> ]]> 智人 <![CDATA[<400> 19]]> gggcggcgag caggcccggg agccgggagg ctgcgggcgg cggcgctgga cccgacgcgg 60 cgagagaggc cccgagatgc cgagcaagaa gaagaagtac aacgcgcggt tcccgccggc 120 gcggatcaag aagatcatgc agacggacga agagattggg aaggtggcgg cggcggtgcc 180 tgtcatcatc tcccgggcgc tcgagctctt cctagagtcg ctgttgaaga aggcctgcca 240 ggtgacccag tcgcggaacg cgaagaccat gaccacatcc cacctgaagc agtgcatcga 300 gctggagcag cagtttgact tcttgaagga cctggtggca tctgttcccg acatgcaggg 360 ggacggggaa gacaaccaca tggatgggga caagggcgcc cgcaggggcc ggaagccagg 420 cagcggcggc cggaagaacg gtgggatggg aacgaaaagc aaggacaaga agctgtccgg 480 gacagactcg gagcaggagg atgaatctga ggacacagat actgatgggg aagaggagac 540 atcacaaccc ccaccccagg ccagccaccc ctctgcccac tttcagagcc ccccgacacc 600 cttcctgccc ttcgcctcta ctctgccttt gcccccagcg cccccgggcc cctcagcacc 660 tgatgaagag gacgaagaag attacgactc ctagcgcctt ctgcccccca gaccatagcc 720 ccttttagtt ggttttagtt gctctggggg gaggagagaa ggtagagctg ttcttaaatt 780 tattaaaaaa aaaaataaaa gggaatctca gtgtctgttc ca 822 <![CDATA[<210> 20]]> <![CDATA[<211> 3137]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 20]]> gagagatccc agcgcgcaga acttggggag ccgccgccgc catccgccgc cgcagccagc 60 ttccgccgcc gcaggaccgg cccctgcccc agcctccgca gccgcggcgc gtccacgccc 120 gcccgcgccc agggcgagtc ggggtcgccg cctgcacgct tctcagtgtt ccccgcgccc 180 cgcatgtaac ccggccaggc ccccgcaact gtgtcccctg cagctccagc cccgggctgc 240 acccccccgc cccgacacca gctctccagc ctgctcgtcc aggatggccg cggccaaggc 300 cgagatgcag ctgatgtccc cgctgcagat ctctgacccg ttcggatcct ttcctcactc 360 gcccaccatg gacaactacc ctaagctgga ggagatgatg ctgctgagca acggggctcc 420 ccagttcctc ggcgccgccg gggccccaga gggcagcggc agcaacagca gcagcagcag 480 cagcgggggc ggtggaggcg gcgggggcgg cagcaacagc agcagcagca gcagcacctt 540 caaccctcag gcggacacgg gcgagcagcc ctacgagcac ctgaccgcag agtcttttcc 600 tgacatctct ctgaacaacg agaaggtgct ggtggagacc agttacccca gccaaaccac 660 tcgactgccc cccatcacct atactggccg cttttccctg gagcctgcac ccaacagtgg 720 caacaccttg tggcccgagc ccctcttcag cttggtcagt ggcctagtga gcatgaccaa 780 cccaccggcc tcctcgtcct cagcaccatc tccagcggcc tcctccgcct ccgcctccca 840 gagcccaccc ctgagctgcg cagtgccatc caacgacagc agtcccattt actcagcggc 900 acccaccttc cccacgccga acactgacat tttccctgag ccacaaagcc aggccttccc 960 gggctcggca gggacagcgc tccagtaccc gcctcctgcc taccctgccg ccaagggtgg 1020 cttccaggtt cccatgatcc ccgactacct gtttccacag cagcaggggg atctgggcct 1080 gggcacccca gaccagaagc ccttccaggg cctggagagc cgcacccagc agccttcgct 1140 aacccctctg tctactatta aggcctttgc cactcagtcg ggctcccagg acctgaaggc 1200 cctcaatacc agctaccagt cccagctcat caaacccagc cgcatgcgca agtaccccaa 1260 ccggcccagc aagacgcccc cccacgaacg cccttacgct tgcccagtgg agtcctgtga 1320 tcgccgcttc tcccgctccg acgagctcac ccgccacatc cgcatccaca caggccagaa 1380 gcccttccag tgccgcatct gcatgcgcaa cttcagccgc agcgaccacc tcaccaccca 1440 catccgcacc cacacaggcg aaaagccctt cgcctgcgac atctgtggaa gaaagtttgc 1500 caggagcgat gaacgcaaga ggcataccaa gatccacttg cggcagaagg acaagaaagc 1560 agacaaaagt gttgtggcct cttcggccac ctcctctctc tcttcctacc cgtccccggt 1620 tgctacctct tacccgtccc cggttactac ctcttatcca tccccggcca ccacctcata 1680 cccatcccct gtgcccacct ccttctcctc tcccggctcc tcgacctacc catcccctgt 1740 gcacagtggc ttcccctccc cgtcggtggc caccacgtac tcctctgttc cccctgcttt 1800 cccggcccag gtcagcagct tcccttcctc agctgtcacc aactccttca gcgcctccac 1860 agggctttcg gacatgacag caaccttttc tcccaggaca attgaaattt gctaaaggga 1920 aaggggaaag aaagggaaaa gggagaaaaa gaaacacaag agacttaaag gacaggagga 1980 ggagatggcc ataggagagg agggttcctc ttaggtcaga tggaggttct cagagccaag 2040 tcctccctct ctactggagt ggaaggtcta ttggccaaca atcctttctg cccacttccc 2100 cttccccaat tactattccc tttgacttca gctgcctgaa acagccatgt ccaagttctt 2160 cacctctatc caaagaactt gatttgcatg gattttggat aaatcatttc agtatcatct 2220 ccatcatatg cctgacccct tgctcccttc aatgctagaa aatcgagttg gcaaaatggg 2280 gtttgggccc ctcagagccc tgccctgcac ccttgtacag tgtctgtgcc atggatttcg 2340 tttttcttgg ggtactcttg atgtgaagat aatttgcata ttctattgta ttatttggag 2400 ttaggtcctc acttggggga aaaaaaaaaa agaaaagcca agcaaaccaa tggtgatcct 2460 ctattttgtg atgatgctgt gacaataagt ttgaaccttt ttttttgaaa cagcagtccc 2520 agtattctca gagcatgtgt cagagtgttg ttccgttaac ctttttgtaa atactgcttg 2580 accgtactct cacatgtggc aaaatatggt ttggtttttc tttttttttt tttttgaaag 2640 tgttttttct tcgtcctttt ggtttaaaaa gtttcacgtc ttggtgcctt ttgtgtgatg 2700 cgccttgctg atggcttgac atgtgcaatt gtgagggaca tgctcacctc tagccttaag 2760 gggggcaggg agtgatgatt tgggggaggc tttgggagca aaataaggaa gagggctgag 2820 ctgagcttcg gttctccaga atgtaagaaa acaaaatcta aaacaaaatc tgaactctca 2880 aaagtctatt tttttaactg aaaatgtaaa tttataaata tattcaggag ttggaatgtt 2940 gtagttacct actgagtagg cggcgatttt tgtatgttat gaacatgcag ttcattattt 3000 tgtggttcta ttttactttg tacttgtgtt tgcttaaaca aagtgactgt ttggcttata 3060 aacacattga atgcgcttta ttgcccatgg gatatgtggt gtatatcctt ccaaaaaatt 3120 aaaacgaaaa taaagta 3137 <![CDATA[<210> 21]]> <![CDATA[<211> 4012]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 21]]> attgctccca gcgccaagct ctgtgtcgcc gccgtcgcct aggcggttgg gggtcggtgg 60 ggcggcgcgg gcgggggtcg ctgcgcgggg cggcgagcct ctgttttgtc tccttctctc 120 cctgtggagc ggctcgggct gctggggagg ccccggctcc ctccggacgc tcggccaacg 180 gcggcggcta gtccgcggcc ctgctgagag ggaaaaggac gccgcggtct tcccaggcgt 240 cgcggagagc agttccaaag aactactggt tcagatttta gctcttccca agttgtgaaa 300 atagtgaagg atgcttagac tacttaacat acaaactgct ttctggttaa tcatctttag 360 aagactggat ttctggatat ctactccact ccatctctat tgacttttaa aacatgataa 420 tgcaaaccta taacactggc aaccatcagt gaacctttaa tttcattgat taatagcgtt 480 tgaagcttcc tcagggaata acaatgacat cagcagtggt tgacagtgga ggtactattt 540 tggagctttc cagcaatgga gtagaaaatc aagaggaaag tgaaaaggtt tctgaatatc 600 cagcagtgat tgtggagcca gttccaagtg ccagattaga gcagggctat gcagcccagg 660 ttctggttta tgatgatgag acttatatga tgcaagatgt ggcagaagaa caagaagttg 720 agaccgagaa tgtggaaaca gtggaagcat cagttcacag cagtaatgca cactgtacag 780 ataagacaat tgaagctgct gaagccctgc ttcatatgga atctcctacc tgcttgaggg 840 attcaagaag tcctgaattc atccatgctg ctatgaggcc agatgtcatt acagaaactg 900 tagtggaggt gtcaactgaa gagtctgaac ccatggatac ctctcctatt ccaacatcac 960 cagatagcca tgaaccaatg aaaaagaaaa aagttggccg taaaccaaag acccagcaat 1020 caccaatttc caatgggtct cctgagttag gtataaagaa gaaaccaaga gaaggaaaag 1080 gaaacacaac ctatttgtgg gagtttcttt tagatctact tcaagataaa aatacttgtc 1140 ccaggtatat taaatggact cagagagaaa aaggcatatt caagctggtg gattcaaagg 1200 ctgtctctaa gctttgggga aagcataaga acaaaccaga catgaactat gaaaccatgg 1260 gacgagcttt gagatactac taccaaaggg gaattcttgc aaaggttgaa ggacagaggc 1320 ttgtatatca gttcaaggat atgccgaaaa acatagtggt catagatgat gacaaaagtg 1380 aaacctgtaa tgaagattta gcaggaacta ctgatgaaaa atcattagaa cgagtgtcac 1440 tgtctgcaga aagtctcctg aaagcagcat cctctgttcg cagtggaaaa aattcatccc 1500 ctataaactg ctccagagca gagaagggtg tagctagagt tgtgaatatc acttcccctg 1560 ggcacgatgc ttcatccagg tctcctacta ccactgcatc tgtgtcagca acagcagctc 1620 caaggacagt tcgtgtggca atgcaggtac ctgttgtaat gacatcattg ggtcagaaaa 1680 tttcaactgt ggcagttcag tcagttaatg caggtgcacc attaataacc agcactagtc 1740 caacaacagc gacctctcca aaggtagtca ttcagacaat ccctactgtg atgccagctt 1800 ctactgaaaa tggagacaaa atcaccatgc agcctgccaa aattattacc atcccagcta 1860 cacagcttgc acagtgtcaa ctgcagacaa agtcaaatct gactggatca ggaagcatta 1920 acattgttgg aaccccattg gctgtgagag cacttacccc tgtttcaata gcccatggta 1980 cacctgtaat gagactatca atgcctactc agcaggcatc tggccagact cctcctcgag 2040 ttatcagtgc agtcataaag gggccagagg ttaaatcgga agcagtggca aaaaagcaag 2100 aacatgatgt gaaaactttg cagctagtag aagaaaaacc agcagatgga aataagacag 2160 tgacccacgt agtggttgtc agtgcgcctt cagctattgc ccttcctgta actatgaaaa 2220 cagaaggact agtgacatgt gagaaataaa atagcagctc caccatggac ttcaggctgt 2280 tagtggcagt actgacataa acatttgcaa gggaagtcat caagaaaagt caaagaagac 2340 tttaaaacat ttttaatgca tatacaaaaa caatcagact tactggaaat aaattaccta 2400 tcccatgttt cagtgggaaa tgaactacat attgagatgc tgacagaaaa ctgcctctta 2460 cagtaggaaa caactgaacc catcaataag aaaaaggatc gaaagggacc aagcagctca 2520 ctacgatatc aagttacact aagacttgga acactaacat tctgtaagag gttatatagt 2580 tttcagtggg aggggttggg atgggtaatc tcattgttac atatagcaat ttttgatgca 2640 ttttatatgc ataccagcaa ttattactgt gttcgcacag ttctcactta actggtgcta 2700 tgtgaagact ctgctaatat aggtatttta gaatgtgaat tgaagaatgg atcccaaaaa 2760 cttcagaaag aggatagcaa aaaaagatct agtgcgattt tatatatata tatatatata 2820 tatacataca tatatatata tcatatagct taagctgatt taaaacaaag gccttagact 2880 aattttcgat tttctttctt gaaataagct aatggcttgt ttgtgtaaag cttttttatt 2940 aaaagaaaaa ttttaaaaat cttgtaccta gcacagtatt gttatagaat atacatgtaa 3000 cattttatat ggtagtttaa gtctgtcagt ttcttaattg tggacaaatt aacagttggc 3060 tctggccttt tgctgtaaca tgcctgtgtc actcacttag ccttggcatt tgtgcagaca 3120 taccattttc agttctgctg tcacttggaa gttcaggctc agcatgaatt tttggcaggt 3180 agctctaata cctggagttt tctttgtttt tttttctttt ttttagttga agtttatgag 3240 ggaaatacca gtgttcagtt ttgaactata atagtttgta tattcaacat ttgaagtata 3300 ttctattttg ttgtactctt gtttcaaagt gtattcaagt aggttttctg aaatatagaa 3360 atgaaattta tcttctgttt tggtctctgg tgatatttta aacaatattt aaaagtcagt 3420 atagaagtgt tttagttagg aagtgataaa acatctctct tctccttccc aactactgca 3480 tgaagaaatt ctacttccat tatattaata tttggcaaat atctgcatgt tgccagtttc 3540 tttctaatta tgatgaacta taatgttctg cttaacgtaa tgaatttagt attttagttg 3600 gctgcactta aagaatttat atttgtaaaa cactttaaac catttgtttc acaatcagac 3660 cttttgtgga ttaaaaagaa caattactct tctagccctt ttacagatta ggaagttaag 3720 gtatctgaag gattacataa actatgtaat tttactactg tctgtcactc catatcttaa 3780 tgctctttct actacaaaga aaagttatct atttttacat gttttagaaa tgtagatgaa 3840 ctcatacata atattttttg tcttttaatt gatcacatac tacttaggtc agaaattgtt 3900 tataacagtt ccctttgtaa tcttttaaac ttttccataa atatattgat gatactttta 3960 tacaaaagct caaagaaaaa ctcacttgat tattttccca tttgggagtt ac 4012 <![CDATA[<210> 22]]> <![CDATA[<211> 2595]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 22]]> gcacaacttg tgaagaagcg aacacttcca tggattgtcc ttggacttag ggcgccctgc 60 ccgccttttg cagaggagaa aaaacttttt tttttttttg cctcccccga gaactttccc 120 cccttctcct ccctgcctct aactccgatc cccccacgcc atctcgccaa aaaaaaaaaa 180 aaaaaaaaaa aagaaaaaaa aagaaaaaaa aagaaaaaaa attaccccaa tccacgcctg 240 caaattcttc tggaaggatt ttcccccctc tcttcaggtt gggcgcgttt ggtgcaagat 300 tctcgggatc ctcggctttg cctctccctc tccctccccc ctcctttcct ttttcctttc 360 ctttcctttc tttcttcctt tccttccccc cacccccacc cccaccccaa acaaacgagt 420 ccccaattct cgtccgtcct cgccgcgggc agcgggcggc ggaggcagcg tgcggcggtc 480 gccaggagct gggagcccag ggcgcccgct cctcggcgca gcatgttcca gccggcgccc 540 aagcgctgct tcaccatcga gtcgctggtg gccaaggaca gtcccctgcc cgcctcgcgc 600 tccgaggacc ccatccgtcc cgcggcactc agctacgcta actccagccc cataaatccg 660 ttcctcaacg gcttccactc ggccgccgcc gccgccgccg gtaggggcgt ctactccaac 720 ccggacttgg tgttcgccga ggcggtctcg cacccgccca accccgccgt gccagtgcac 780 ccggtgccgc cgccgcacgc cctggccgcc caccccctac cctcctcgca ctcgccacac 840 cccctattcg cctcgcagca gcgggatccg tccaccttct acccctggct catccaccgc 900 taccgatatc tgggtcatcg cttccaaggg aacgacacta gccccgagag tttccttttg 960 cacaacgcgc tggcccgaaa gcccaagcgg atccgaaccg ccttctcccc gtcccagctt 1020 ctaaggctgg aacacgcctt tgagaagaat cactacgtgg tgggcgccga aaggaagcag 1080 ctggcacaca gcctcagcct cacggaaact caggtaaaag tatggtttca gaaccgaaga 1140 acaaagttca aaaggcagaa gctggaggaa gaaggctcag attcgcaaca aaagaaaaaa 1200 gggacgcacc atattaaccg gtggagaatc gccaccaagc aggcgagtcc ggaggaaata 1260 gacgtgacct cagatgatta aaaacataaa cctaacccca cagaaacgga caacatggag 1320 caaaagagac agggagaggt ggagaaggaa aaaaccctac aaaacaaaaa caaaccgcat 1380 acacgttcac cgagaaaggg agagggaatc ggagggagca gcggaatgcg gcgaagactc 1440 tggacagcga gggcacaggg tcccaaaccg aggccgcgcc aagatggcag aggatggagg 1500 ctccttcatc aacaagcgac cctcgtctaa agaggcagct gagtgagaga cacagagaga 1560 aggagaaaga gggagggaga gagagaaaga gagagaaaga gagagagaga gagagagaga 1620 gaaagctgaa cgtgcactct gacaagggga gctgtcaatc aaacaccaaa ccggggagac 1680 aagatgattg gcaggtattc cgtttatcac agtccactta aaaaatgatg atgatgataa 1740 aaaccacgac ccaaccaggc acaggacttt tttgtttttt gcacttcgct gtgtttcccc 1800 cccatcttta aaaataatta gtaataaaaa acaaaaattc catatctagc cccatcccac 1860 acctgtttca aatccttgaa atgcatgtag cagttgttgg gcgaatggtg tttaaagacc 1920 gaaaatgaat tgtaattttc ttttcctttt aaagacaggt tctgtgtgct ttttattttg 1980 attttttttc ccaagaaatg tgcagtctgt aaacactttt tgataccttc tgatgtcaaa 2040 gtgattgtgc aagctaaatg aagtaggctc agcgatagtg gtcctcttac agagaaacgg 2100 ggagcaggac gacggggggg ctgggggtgg cgggggaggg tgcccacaaa aagaatcagg 2160 acttgtactg ggaaaaaaac ccctaaatta attatatttc ttggacattc cctttcctaa 2220 catcctgagg cttaaaaccc tgatgcaaac ttctcctttc agtggttgga gaaattggcc 2280 gagttcaacc attcactgca atgcctattc caaactttaa atctatctat tgcaaaacct 2340 gaaggactgt agttagcggg gatgatgtta agtgtggcca agcgcacggc ggcaagtttt 2400 caagcactga gtttctattc caagatcata gacttactaa agagagtgac aaatgcttcc 2460 ttaatgtctt ctataccaga atgtaaatat ttttgtgttt tgtgttaatt tgttagaatt 2520 ctaacacact atatacttcc aagaagtatg tcaatgtcaa tattttgtca ataaagattt 2580 atcaatatgc cctca 2595 <![CDATA[<210> 23]]> <![CDATA[<211> 2274]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 23]]> gtcagctgga ggaagcggag taggaagcgg ccgcgatgtc cttttgtgtc ctacaagcag 60 ccggcggcgc cgccgagtga ggggacgcgg cgcggtgggg cggcgcggcc cgaggaggcg 120 gcggaggagg ggccgcccgc ggcccccggc tcactccggc actccgggcc gctcggcccc 180 catgcctgcc cgaccgcgct gccggagccc caggtgacca gcgccatgtc cagccaggtg 240 gtgggcattg agcctctcta catcaaggca gagccggcca gccctgacag tccaaagggt 300 tcctcggaga cagagaccga gcctcctgtg gccctggccc ctggtccagc tcccactcgc 360 tgcctcccag gccacaagga agaggaggat ggggaggggg ctgggcctgg cgagcagggc 420 ggtgggaagc tggtgctcag ctccctgccc aagcgcctct gcctggtctg tggggacgtg 480 gcctccggct accactatgg tgtggcatcc tgtgaggcct gcaaagcctt cttcaagagg 540 accatccagg ggagcatcga gtacagctgt ccggcctcca acgagtgtga gatcaccaag 600 cggagacgca aggcctgcca ggcctgccgc ttcaccaagt gcctgcgggt gggcatgctc 660 aaggagggag tgcgcctgga ccgcgtccgg ggtgggcggc agaagtacaa gcggcggccg 720 gaggtggacc cactgccctt cccgggcccc ttccctgctg ggcccctggc agtcgctgga 780 ggcccccgga agacagcagc cccagtgaat gcactggtgt ctcatctgct ggtggttgag 840 cctgagaagc tctatgccat gcctgacccc gcaggccctg atgggcacct cccagccgtg 900 gctaccctct gtgacctctt tgaccgagag attgtggtca ccatcagctg ggccaagagc 960 atcccaggct tctcatcgct gtcgctgtct gaccagatgt cagtactgca gagcgtgtgg 1020 atggaggtgc tggtgctggg tgtggcccag cgctcactgc cactgcagga tgagctggcc 1080 ttcgctgagg acttagtcct ggatgaagag ggggcacggg cagctggcct gggggaactg 1140 ggggctgccc tgctgcaact agtgcggcgg ctgcaggccc tgcggctgga gcgagaggag 1200 tatgttctac taaaggcctt ggcccttgcc aattcagact ctgtgcacat cgaagatgcc 1260 gaggctgtgg agcagctgcg agaagctctg cacgaggccc tgctggagta tgaagccggc 1320 cgggctggcc ccggaggggg tgctgagcgg cggcgggcgg gcaggctgct gctcacgcta 1380 ccgctcctcc gccagacagc gggcaaagtg ctggcccatt tctatggggt gaagctggag 1440 ggcaaggtgc ccatgcacaa gctgttcttg gagatgctcg aggccatgat ggactgaggc 1500 aaggggtggg actggtgggg gttctggcag gacctgccta gcatggggtc agccccaagg 1560 gctggggcgg agctggggtc tgggcagtgc cacagcctgc tggcagggcc agggcaatgc 1620 catcagcccc tgggaacagg ccccacgccc tctcctcccc ctcctagggg gtgtcagaag 1680 ctgggaacgt gtgtccaggc tctgggcaca gtgctgcccc ttgcaagcca taacgtgccc 1740 ccagagtgta gggggccttg cggaagccat agggggctgc acgggatgcg tgggaggcag 1800 aaacctatct cagggaggga aggggatgga ggccagagtc tcccagtggg tgatgctttt 1860 gctgctgctt aatcctaccc cctcttcaaa gcagagtggg acttggagag caaaggccca 1920 tgcccccttc gctcctcctc tcatcatttg cattgggcat tagtgtcccc ccttgaagca 1980 ataactccaa gcagactcca gcccctggac ccctggggtg gccagggctt ccccatcagc 2040 tcccaacgag cctcctcagg gggtaggaga gcactgcctc tatgccctgc agagcaataa 2100 cactatattt atttttgggt ttggccaggg aggcgcaggg acatggggca agccagggcc 2160 cagagccctt ggctgtacag agactctatt ttaatgtata tttgctgcaa agagaaaccg 2220 cttttggttt taaaccttta atgagaaaaa aatatataat accgagctca aaaa 2274 <![CDATA[<210> 24]]> <![CDATA[<211> 3668]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 24]]> ggttacttcc tccagagact gacgagtgcg gtgtcgctcc agctcagagc tcccggagcc 60 gcccggccag cgtccggcct ccctgatcgt ctctggccgg cgccctcgcc ctcgcccggc 120 gcgcaccgag cagccgcggg cgccgagcag ccaccgtccc gaccaagcgc cggccctgcc 180 cgcagcggca ggatgaatga tttcggaatc aagaatatgg accaggtagc ccctgtggct 240 aacagttaca gagggacact caagcgccag ccagcctttg acacctttga tgggtccctg 300 tttgctgttt ttccttctct aaatgaagag caaacactgc aagaagtgcc aacaggcttg 360 gattccattt ctcatgactc cgccaactgt gaattgcctt tgttaacccc gtgcagcaag 420 gctgtgatga gtcaagcctt aaaagctacc ttcagtggct tcaaaaagga acagcggcgc 480 ctgggcattc caaagaaccc ctggctgtgg agtgagcaac aggtatgcca gtggcttctc 540 tgggccacca atgagttcag tctggtgaac gtgaatctgc agaggttcgg catgaatggc 600 cagatgctgt gtaaccttgg caaggaacgc tttctggagc tggcacctga ctttgtgggt 660 gacattctct gggaacatct ggagcaaatg atcaaagaaa accaagaaaa gacagaagat 720 caatatgaag aaaattcaca cctcacctcc gttcctcatt ggattaacag caatacatta 780 ggttttggca cagagcaggc gccctatgga atgcagacac agaattaccc caaaggcggc 840 ctcctggaca gcatgtgtcc ggcctccaca cccagcgtac tcagctctga gcaggagttt 900 cagatgttcc ccaagtctcg gctcagctcc gtcagcgtca cctactgctc tgtcagtcag 960 gacttcccag gcagcaactt gaatttgctc accaacaatt ctgggactcc caaagaccac 1020 gactcccctg agaacggtgc ggacagcttc gagagctcag actccctcct ccagtcctgg 1080 aacagccagt cgtccttgct ggatgtgcaa cgggttcctt ccttcgagag cttcgaagat 1140 gactgcagcc agtctctctg cctcaataag ccaaccatgt ctttcaagga ttacatccaa 1200 gagaggagtg acccagtgga gcaaggcaaa ccagttatac ctgcagctgt gctggccggc 1260 ttcacaggaa gtggacctat tcagctgtgg cagtttctcc tggagctgct atcagacaaa 1320 tcctgccagt cattcatcag ctggactgga gacggatggg agtttaagct cgccgacccc 1380 gatgaggtgg cccgccggtg gggaaagagg aaaaataagc ccaagatgaa ctacgagaag 1440 ctgagccggg gcttacgcta ctattacgac aagaacatca tccacaagac gtcggggaag 1500 cgctacgtgt accgcttcgt gtgcgacctc cagaacttgc tggggttcac gcccgaggaa 1560 ctgcacgcca tcctgggcgt ccagcccgac acggaggact gaggtcgccg ggaccaccct 1620 gagccggccc caggctcgtg gactgagtgg gaagcccatc ctgaccagct gctccgagga 1680 cccaggaaag gcaggattga aaatgtccag gaaagtggcc aagaagcagt ggccttattg 1740 catcccaaac cacgcctctt gaccaggctg cctcccttgt ggcagcaacg gcacagctaa 1800 ttctactcac agtgctttta agtgaaaatg gtcgagaaag aggcaccagg aagccgtcct 1860 ggcgcctggc agtccgtggg acgggatggt tctggctgtt tgagattctc aaaggagcga 1920 gcatgtcgtg gacacacaca gactattttt agattttctt ttgccttttg caaccaggaa 1980 cagcaaatgc aaaaactctt tgagagggta ggagggtggg aaggaaacaa ccatgtcatt 2040 tcagaagtta gtttgtatat attattataa tcttataatt gttctcagaa tcccttaaca 2100 gttgtattta acagaaattg tatattgtaa tttaaaataa ttatataact gtatttgaaa 2160 taagaattca gacatctgag gttttatttc atttttcaat agcacatatg gaattttgca 2220 aagatttaat ctgccaaggg ccgactaaga gaagttgtaa agtatgtatt atttacattt 2280 aatagactta cagggataag gcctgtgggg ggtaatccct gctttttgtg tttttttgtt 2340 tgtttgtttg tttgtttttg gggggttttc ttgccttggt tgtctggcaa ggactttgta 2400 catttgggag tttttatgag aaacttaaat gttattatct gggcttatat ctggcctctg 2460 ctttctcctt taattgtaaa gtaaaagcta taaagcagta tttttcttga caaatggcat 2520 atgttttcca cttctttgca tgcgtttaag tcagtttata cacaaaatgg attttatttt 2580 ttagtttaac tgtgtttctc cgacagctca cctctctctg accacccagc catttccttc 2640 ctgtgctcca cgttcttctg tgtgattaaa ataagaatat tatttttgga aatatgcaac 2700 tccttttcag agatcaggag ggatttatgt agcagctatt tttactgcaa aagtaattca 2760 ctggaaaaaa aatgtaattt gtaagaaagc tttattttta tctcagctct atgtaaagtt 2820 aaagttactg tacagagctg aaggacgggg ggcggtaggg gtcttgatga aacctcttga 2880 acgaagcaca gtttgtccca tctttgttca ctcgtgtgtc tcaaccatct taatagcatg 2940 ctgctccttt ttgctcagtg tccacagcaa gatgacgtga ttcttatttt cttggacaca 3000 gactattctg aggcacagag cggggactta agatgggaaa gagaaagcat cggagccatt 3060 cattcggaga aaacgttttg atcaaaatgg agacttttgt agtcgtttca aaagagcacc 3120 tgagtcatgt gtattcccgg cctttataaa tgacccggtc aagttggttt caaagtccga 3180 caggcttgtc tgtttactag ctgcgtggcc ttggacgggt ggctgacatc tgtaaagaat 3240 cctcctgtga tgaaactgag gaatcgggtg gccgggcaag ctgggaagag caaagccaga 3300 gctgcgctgc ctcaataccc acaaaagacc attcccagta tacataagca caggatgttt 3360 ttctcaagag ggatgtattt atcacttgga catctgttta taatataaac agacatgtga 3420 ctgggaacat cttgctgcca aaagaatcct aggcagtggc tcattgtatg tgaggttgaa 3480 ccacgtgaaa ttgccaatat taggctggct tttatctaca aagaaggagt ttcatggggt 3540 tcagcctaac agttatggaa actacagtcc ttataaacca ttggcatggt aataaacaga 3600 tcttaagtat aaaaattttg taattgggcc tttactctct caataataaa gtattttgtt 3660 tatataaa 3668 <![CDATA[<210> 25]]> <![CDATA[<211> 2104]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 25]]> aaccgcatct gcagcgagca tctgagaagc caagactgag ccggcggccg cggcgcagcg 60 aacgagcagt gaccgtgctc ctacccagct ctgctccaca gcgcccacct gtctccgccc 120 ctcggcccct cgcccggctt tgcctaaccg ccacgatgat gttctcgggc ttcaacgcag 180 actacgaggc gtcatcctcc cgctgcagca gcgcgtcccc ggccggggat agcctctctt 240 actaccactc acccgcagac tccttctcca gcatgggctc gcctgtcaac gcgcaggact 300 tctgcacgga cctggccgtc tccagtgcca acttcattcc cacggtcact gccatctcga 360 ccagtccgga cctgcagtgg ctggtgcagc ccgccctcgt ctcctccgtg gccccatcgc 420 agaccagagc ccctcaccct ttcggagtcc ccgccccctc cgctggggct tactccaggg 480 ctggcgttgt gaagaccatg acaggaggcc gagcgcagag cattggcagg aggggcaagg 540 tggaacagtt atctccagaa gaagaagaga aaaggagaat ccgaagggaa aggaataaga 600 tggctgcagc caaatgccgc aaccggagga gggagctgac tgatacactc caagcggaga 660 cagaccaact agaagatgag aagtctgctt tgcagaccga gattgccaac ctgctgaagg 720 agaaggaaaa actagagttc atcctggcag ctcaccgacc tgcctgcaag atccctgatg 780 acctgggctt cccagaagag atgtctgtgg cttcccttga tctgactggg ggcctgccag 840 aggttgccac cccggagtct gaggaggcct tcaccctgcc tctcctcaat gaccctgagc 900 ccaagccctc agtggaacct gtcaagagca tcagcagcat ggagctgaag accgagccct 960 ttgatgactt cctgttccca gcatcatcca ggcccagtgg ctctgagaca gcccgctccg 1020 tgccagacat ggacctatct gggtccttct atgcagcaga ctgggagcct ctgcacagtg 1080 gctccctggg gatggggccc atggccacag agctggagcc cctgtgcact ccggtggtca 1140 cctgtactcc cagctgcact gcttacacgt cttccttcgt cttcacctac cccgaggctg 1200 actccttccc cagctgtgca gctgcccacc gcaagggcag cagcagcaat gagccttcct 1260 ctgactcgct cagctcaccc acgctgctgg ccctgtgagg gggcagggaa ggggaggcag 1320 ccggcaccca caagtgccac tgcccgagct ggtgcattac agagaggaga aacacatctt 1380 ccctagaggg ttcctgtaga cctagggagg accttatctg tgcgtgaaac acaccaggct 1440 gtgggcctca aggacttgaa agcatccatg tgtggactca agtccttacc tcttccggag 1500 atgtagcaaa acgcatggag tgtgtattgt tcccagtgac acttcagaga gctggtagtt 1560 agtagcatgt tgagccaggc ctgggtctgt gtctcttttc tctttctcct tagtcttctc 1620 atagcattaa ctaatctatt gggttcatta ttggaattaa cctggtgctg gatattttca 1680 aattgtatct agtgcagctg attttaacaa taactactgt gttcctggca atagtgtgtt 1740 ctgattagaa atgaccaata ttatactaag aaaagatacg actttatttt ctggtagata 1800 gaaataaata gctatatcca tgtactgtag tttttcttca acatcaatgt tcattgtaat 1860 gttactgatc atgcattgtt gaggtggtct gaatgttctg acattaacag ttttccatga 1920 aaacgtttta ttgtgttttt aatttattta ttaagatgga ttctcagata tttatatttt 1980 tattttattt ttttctacct tgaggtcttt tgacatgtgg aaagtgaatt tgaatgaaaa 2040 atttaagcat tgtttgctta ttgttccaag acattgtcaa taaaagcatt taagttgaat 2100 gcga 2104 <![CDATA[<210> 26]]> <![CDATA[<211> 3775]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 26]]> attcataaga ctcagagcta cggccacggc agggacacgc ggaaccaaga cttggaaact 60 tgattgttgt ggttcttctt gggggttatg aaatttcatt aatctttttt tttccgggga 120 gaaagttttt ggaaagattc ttccagatat ttcttcattt tcttttggag gaccgactta 180 ctttttttgg tcttctttat tactcccctc cccccgtggg acccgccgga cgcgtggagg 240 agaccgtagc tgaagctgat tctgtacagc gggacagcgc tttctgcccc tgggggagca 300 acccctccct cgcccctggg tcctacggag cctgcacttt caagaggtac agcggcatcc 360 tgtgggggcc tgggcaccgc aggaagactg cacagaaact ttgccattgt tggaacggga 420 cgttgctcct tccccgagct tccccggaca gcgtactttg aggactcgct cagctcaccg 480 gggactccca cggctcaccc cggacttgca ccttacttcc ccaacccggc catagccttg 540 gcttcccggc gacctcagcg tggtcacagg ggcccccctg tgcccaggga aatgtttcag 600 gctttccccg gagactacga ctccggctcc cggtgcagct cctcaccctc tgccgagtct 660 caatatctgt cttcggtgga ctccttcggc agtccaccca ccgccgccgc ctcccaggag 720 tgcgccggtc tcggggaaat gcccggttcc ttcgtgccca cggtcaccgc gatcacaacc 780 agccaggacc tccagtggct tgtgcaaccc accctcatct cttccatggc ccagtcccag 840 gggcagccac tggcctccca gcccccggtc gtcgacccct acgacatgcc gggaaccagc 900 tactccacac caggcatgag tggctacagc agtggcggag cgagtggcag tggtgggcct 960 tccaccagcg gaactaccag tgggcctggg cctgcccgcc cagcccgagc ccggcctagg 1020 agaccccgag aggagacgct caccccagag gaagaggaga agcgaagggt gcgccgggaa 1080 cgaaataaac tagcagcagc taaatgcagg aaccggcgga gggagctgac cgaccgactc 1140 caggcggaga cagatcagtt ggaggaagaa aaagcagagc tggagtcgga gatcgccgag 1200 ctccaaaagg agaaggaacg tctggagttt gtgctggtgg cccacaaacc gggctgcaag 1260 atcccctacg aagaggggcc cgggccgggc ccgctggcgg aggtgagaga tttgccgggc 1320 tcagcaccgg ctaaggaaga tggcttcagc tggctgctgc cgcccccgcc accaccgccc 1380 ctgcccttcc agaccagcca agacgcaccc cccaacctga cggcttctct ctttacacac 1440 agtgaagttc aagtcctcgg cgaccccttc cccgttgtta acccttcgta cacttcttcg 1500 tttgtcctca cctgcccgga ggtctccgcg ttcgccggcg cccaacgcac cagcggcagt 1560 gaccagcctt ccgatcccct gaactcgccc tccctcctcg ctctgtgaac tctttagaca 1620 cacaaaacaa acaaacacat gggggagaga gacttggaag aggaggagga ggaggagaag 1680 gaggagagag aggggaagag acaaagtggg tgtgtggcct ccctggctcc tccgtctgac 1740 cctctgcggc cactgcgcca ctgccatcgg acaggaggat tccttgtgtt ttgtcctgcc 1800 tcttgtttct gtgccccggc gaggccggag agctggtgac tttggggaca gggggtggga 1860 aggggatgga cacccccagc tgactgttgg ctctctgacg tcaacccaag ctctggggat 1920 gggtggggag gggggcgggt gacgcccacc ttcgggcagt cctgtgtgag gattaaggga 1980 cgggggtggg aggtaggctg tggggtgggc tggagtcctc tccagagagg ctcaacaagg 2040 aaaaatgcca ctccctaccc aatgtctccc acacccaccc tttttttggg gtgcctaggt 2100 tggtttcccc tgcactcccg accttagctt attgatccca catttccatg gtgtgagatc 2160 ctctttactc tgggcagaag tgagcccccc ccttaaaggg aattcgatgc ccccctagaa 2220 taatctcatc cccccacccg acttcttttg aaatgtgaac gtccttcctt gactgtctag 2280 ccactccctc ccagaaaaac tggctctgat tggaatttct ggcctcctaa ggctccccac 2340 cccgaaatca gcccccagcc ttgtttctga tgacagtgtt atcccaagac cctgccccct 2400 gccagccgac cctcctggcc ttcctcgttg ggccgctctg atttcaggca gcaggggctg 2460 ctgtgatgcc gtcctgctgg agtgatttat actgtgaaat gagttggcca gattgtgggg 2520 tgcagctggg tggggcagca cacctctggg gggataatgt ccccactccc gaaagccttt 2580 cctcggtctc ccttccgtcc atcccccttc ttcctcccct caacagtgag ttagactcaa 2640 gggggtgaca gaaccgagaa gggggtgaca gtcctccatc cacgtggcct ctctctctct 2700 cctcaggacc ctcagccctg gcctttttct ttaaggtccc ccgaccaatc cccagcctag 2760 gacgccaact tctcccaccc cttggcccct cacatcctct ccaggaaggg agtgaggggc 2820 tgtgacattt ttccggagaa gatttcagag ctgaggcttt ggtaccccca aacccccaat 2880 atttttggac tggcagactc aaggggctgg aatctcatga ttccatgccc gagtccgccc 2940 atccctgacc atggttttgg ctctcccacc ccgccgttcc ctgcgcttca tctcatgagg 3000 atttctttat gaggcaaatt tatatttttt aatatcgggg ggtggaccac gccgccctcc 3060 atccgtgctg catgaaaaac attccacgtg ccccttgtcg cgcgtctccc atcctgatcc 3120 cagacccatt ccttagctat ttatcccttt cctggtttcc gaaaggcaat tatatctatt 3180 atgtataagt aaatatatta tatatggatg tgtgtgtgtg cgtgcgcgtg agtgtgtgag 3240 cgcttctgca gcctcggcct aggtcacgtt ggccctcaaa gcgagccgtt gaattggaaa 3300 ctgcttctag aaactctggc tcagcctgtc tcgggctgac ccttttctga tcgtctcggc 3360 ccctctgatt gttcccgatg gtctctctcc ctctgtcttt tctcctccgc ctgtgtccat 3420 ctgaccgttt tcacttgtct cctttctgac tgtccctgcc aatgctccag ctgtcgtctg 3480 actctgggtt cgttggggac atgagatttt attttttgtg agtgagactg agggatcgta 3540 gatttttaca atctgtatct ttgacaattc tgggtgcgag tgtgagagtg tgagcagggc 3600 ttgctcctgc caaccacaat tcaatgaatc cccgaccccc ctaccccatg ctgtacttgt 3660 ggttctcttt ttgtattttg catctgaccc cggggggctg ggacagattg gcaatgggcc 3720 gtcccctctc cccttggttc tgcactgttg ccaataaaaa gctcttaaaa acgca 3775 <![CDATA[<210> 27]]> <![CDATA[<211> 6713]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 27]]> gtagtgactc atctcgggca gagcgctagg gctccgagcg aaccagcgag cgagcgaacg 60 agcggcgctc ggcggggaca gaaagaggga gagagagaga gagagagagg gagaggcgcg 120 gccgggcgag gcgggcccgt ccgggagcgg gctccgggga aggggtgcgg gtctgggcgc 180 cggagcgggg agcggggccg cgtccctctc agcgccagct ctacttgagc cccacgagcc 240 gctgtccccc tggcgcgctc ggggccgcgg gacgggcgca cgccgccttc tcctagtcaa 300 gtatccgagc cgccccgaaa ctcgggcggc gagtcggcca cgggaagttt attctccggc 360 tccttttcta aaaggaagaa acagaagttt ctcccagcgg acagcttttc tttccgcctt 420 tttggccctg tctgaaatcg ggggtcccca gggctggcag gccaggctcg ctgggctcct 480 aatctttttt ttaatttcca atttttgatt gggccgtggg tccccgctga gctccggctg 540 cgcgcggggg cgggagggcg cgcgcagggg agggaccgag agacgcgccg actttttaga 600 gggagggatc gggtggacaa ctggtcccgc ggcgctcgca gagccggaaa gaagtgctgt 660 aagggacgct cgggggacgc tgttcctgag gtgtcgccgc ctccctgtcc tcgccctccg 720 cggtggggga gaaacccagg agcgaagccc agagcccgcg gcgcggccgg cggacgaacg 780 agcgcgcagc agccggtgcg cggccgcggc gagggcgggg gaagaaaaac accctgtttc 840 ctctccggcc cccaccgcgg atcatgtacc aggattatcc cgggaacttt gacacctcgt 900 cccggggcag cagcggctct cctgcgcacg ccgagtccta ctccagcggc ggcggcggcc 960 agcagaaatt ccgggtagat atgcctggct caggcagtgc attcatcccc accatcaacg 1020 ccatcacgac cagccaggac ctgcagtgga tggtgcagcc cacagtgatc acctccatgt 1080 ccaacccata ccctcgctcg cacccctaca gccccctgcc gggcctggcc tctgtccctg 1140 gacacatggc cctcccaaga cctggcgtga tcaagaccat tggcaccacc gtgggccgca 1200 ggaggagaga tgagcagctg tctcctgaag aggaggagaa gcgtcgcatc cggcgggaga 1260 ggaacaagct ggctgcagcc aagtgccgga accgacgccg ggagctgaca gagaagctgc 1320 aggcggagac agaggagctg gaggaggaga agtcaggcct gcagaaggag attgctgagc 1380 tgcagaagga gaaggagaag ctggagttca tgttggtggc tcacggccca gtgtgcaaga 1440 ttagccccga ggagcgccga tcgcccccag cccctgggct gcagcccatg cgcagtgggg 1500 gtggctcggt gggcgctgta gtggtgaaac aggagcccct ggaagaggac agcccctcgt 1560 cctcgtcggc ggggctggac aaggcccagc gctctgtcat caagcccatc agcattgctg 1620 ggggcttcta cggtgaggag cccctgcaca cccccatcgt ggtgacctcc acacctgctg 1680 tcactccggg cacctcgaac ctcgtcttca cctatcctag cgtcctggag caggagtcac 1740 ccgcatctcc ctccgaatcc tgctccaagg ctcaccgcag aagcagtagc agcggggacc 1800 aatcatcaga ctccttgaac tcccccactc tgctggctct gtaacccagt gcacctccct 1860 ccccagctcc ggagggggtc ctcctcgctc ctccttccca gggaccagca ccttcaagcg 1920 ctccagggcc gtgagggcaa gagggggacc tgccaccagg gagcttcctg gctctggggg 1980 acccaggtgg gacttagcag tgagtattgg aagacttggg ttgatctctt agaagccatg 2040 ggacctcctc cctcattcat cttgcaagca aatcccattt cttgaaaagc cttggagaac 2100 tcggtttggt agacttggac atctctctgg cttctgaaga gcctgaagct ggcctggacc 2160 attcctgtcc ctttgttacc atactgtctc tggagtgatg gtgtccttcc ctgccccacc 2220 acgcatgctc agtgcctttt ggtttcacct tccctcgact tgaccctttc ctcccccagc 2280 gtcagtttca ctccctcttg gtttttatca aatttgccat gacatttcat ctgggtggtc 2340 tgaatattaa agctcttcat ttctggagat ggggcagcag gtggctcttc tgctggggct 2400 gacttgtcca gaaggggaca aagtgcaata cagagccttc cctaccctga cgcctcccag 2460 tcatcatctc cagaactccc agcggggctc cctgagctct caaggagatg ctgccatcac 2520 tgggaggctc agaggaccct tcctgcccac cttcggagac ggcttctgga ggaacggctt 2580 ggccagaaga cagggtgtga gtgagacagt ggggcacagg ttgggtttgc caaacgccta 2640 attaccaggc caggaagcat gccaacaaag ccacacgggt gtcctagcca gcttcccttc 2700 acctggtgtc ttgagtaggg cgtctcctgt aattactgcc ttgccattct gcccctggac 2760 ccttctctcc ggaccaggga ggcgtccctc cctaggagcc acacattata ctccaagtcc 2820 ctgccgggct ccgcctttcc cccaccctgg ctctcagggt gacgccaccc acagagattt 2880 aatgagcgtg ggcctggacc ttccccagat gctgccaggc agcccctccc caagcctcaa 2940 agaagcattt gctgaggatg gagaggcagg ggagggaggc gggaggccgt cactggagtg 3000 gcgtctgcag cagctgctgc cccagcaccc gctcagcctg tcctggctgc tcacctcccc 3060 gcagggcacc gggcctttcc tgccctctgt ggtcatctgc cacctgctgg atcaagtgct 3120 ttctctttta cactcccctg tccccacccc agtgcactct tctggcccag gcagcaagca 3180 agctgtgaac agctggcctg agctgtcgct gtggcttgtg gctcatgcgc cattcctggt 3240 tgtctgttga atctttctgg ctgctggaat tggagatagg atgttttgct tcccactgca 3300 ggagagctgc cccctttcac ggggttgggg aagggtcccc ctggcctcca gcaggagcac 3360 agctcagcag ggtccctgct gcccacccct ctgagccttt tctccccagg gtatggctcc 3420 tgctgagttt cttgtccagc agggccttga caggaatcca gggagtagct cctggccaga 3480 accagcctct gcggggcttg tgctctgcaa agactctgct gctggggatt cagctctaga 3540 ggtcacagta tcctcgtttg aaagataatt aagatccccc gtggagaaag cagtgacaca 3600 ttcacacagc tgttccctcg catgttattt catgaacatg acctgttttc gtgcactaga 3660 cacacagagt ggaacagccg tatgcttaaa gtacatgggc cagtgggact ggaagtgacc 3720 tgtacaagtg atgcagaaag gagggtttca aagaaaaagg attttgttta aaatacttta 3780 aaaatgttat ttcctgcatc ccttggctgt gatgcccctc tcccgatttc ccaggggctc 3840 tgggagggac ccttctaaga agattgggca gttgggtttc tggcttgaga tgaatccaag 3900 cagcagaatg agccaggagt agcaggagat gggcaaagaa aactggggtg cactcagctc 3960 tcacaggggt aatcatctca agtggtattt gtagccaagt gggagctatt ttcttttttg 4020 tgcatataga tatttcttaa atgaagctgc tttcttgtct tttatttcta aaagccccct 4080 tataccccac tttgtgcagc aaagatcccc gtgcaggtca cagcctgatt tgtggccagg 4140 ctggacaaat tcctgaggca caacttggct tcagttcaga tttcaagctg tgttggtgtt 4200 gggaccagca gaaggcaaac gtccagccaa cacacaggac tgtaagagga ctctgagcta 4260 cgtgccctgt gaagaccccc aggctttgtc ataggaggtc gttcagcttc cccaaagtca 4320 gaggtgattt gatttgggga agactgaata ttcacaccta agtcgtgagc atatcctgag 4380 ttttacttcc ttatggcttg ccctccaagt tctctctctc atacacacac acacccttgc 4440 tccagaatca ccagacacct ccatggctcc agctatggga acagctgcat tggggctgcc 4500 tttctgtttg gcttaggaac ttctgtgctt cttgtggctc cactcgcgag gcagctcgga 4560 ggtgtggact ccgattgggc tgcaggcagc tctgggacgg cacagggcgg gcgctctgat 4620 cagctcgtgt aaaacacacc gtcttcttgg cctcctggcc agtctttctg cgaatagtcc 4680 tctccctggc cagttgaatg ggggaagctg ctggcacagg aaggagaggc gatcccggct 4740 gaggcttagg aaattgctgg agccggctcc aagcagataa ttcactgggg aggttttcag 4800 agtcaaacat cattctgcct gtgttggggg ccaggtgtgt cacacaagca tctcaaagtc 4860 aaaagccatc tggggctgct gcttctgttt ctcaggctct ggggaaagga atctccctct 4920 cctctcactt gattccaagt gtggttgaat tgtctggagc actgggactt tttttctctt 4980 ttccttgatg gaccaacagt gcaaatgcaa tctcgccatt taactttcag gtcgatttcc 5040 tttcctgatc agacatcttt gtgccccctt taggaaggaa aagaatacac ctacgatgtg 5100 ccaggcactg tgttaggcgc ttttatatag atcctcgtta ggatgagact aagggatgag 5160 gacatctctt tataaaaggc ccctaagtaa tggataaaca gaaacactta gaggtgagaa 5220 ggtctgtctt caagatccaa ggtaagattg ccttcagtct gatgtttgtt ctcaaggact 5280 tatcccctac aatattctcc cactccatac ttctccttct accccaccat gtgctcccgt 5340 gcactcctca gatggtcaga ggggtaaccc aagtccttag agaatttggg gaccaataga 5400 atatgtgatg tgtgaatttt ctttaaaaaa cttaaggagt ctttgctacc ttctgcttgt 5460 tgagttgttt tggcattcat attaaaagcc agcatctcac tatttattga caggttgggc 5520 tgtgtgtgtg cgcatgtgtg tatacatttc caggcgtgcc tgtgtcctgt agctttttaa 5580 aaggaaaccc agtcatccca ctatgaatct ggcatcttct tatgcttcta gtgttttggc 5640 catacatcaa ccaaggggtt taatttatcc aatgcttgac gacatgttca ggaggggctg 5700 gatcaaattt tgagagggtt atgggaaagg gagggggaga agaaattgac atttatttta 5760 ttatttattt taaatgttta catcttcttt atgttgtatc aagcctgaat agaaactgat 5820 agcattaaaa tactccgttc ctctctctct tctcgcttcc tttttttttt tttttttaaa 5880 tttaggataa cacatttttg tttctaaagt gatttgtgat ttgtgctgta taaactgtat 5940 aaaaggttct gtttttaaag gtggattttc attcctctgg ggacagtggt cgccaagaca 6000 tctacattgt aagagaacac agtggaagat cctgtcctga ttctcaaaaa ttattttctc 6060 tgtatgatta aaagtttatt ccatttattt tagtttgtgt ttacttgatt ttgaggaaga 6120 aaatatttga ctttgtgtaa agagtagggt atcagggtgt cttttctgcc gtgggagatg 6180 tgtatatata tagtattttg gtgtatagta gaaaataagc tttgtgcatc tgtatttgag 6240 atatgttaat gacgtggagt aaagtcagct gtaagactct ggaggcaaac aagttgtata 6300 tggttcatat ggctctatgg ggaatttaat tacctttctg ggcacttttt tttttttttt 6360 ttttttaagt aatggtgaaa tggtcccatt ggagagtctc ctaaatagac cttccaggca 6420 gaaccgcaag ctcaaaatct ttgtatagtt ttgaaaattg aggagtagct ttgtttggaa 6480 gcctttctgg tggtggtttt tgttgttgtt gttgttttgt tgttttacta tatgtaatac 6540 aagcctacag tatttgcact aaagaaagct tgttagaaaa agcttgctgc tatggaagaa 6600 agaacatatt aaaacttctt tcccttgcga tttttttggg ggaggggggt tagcatttcc 6660 actttcagtt gagtagcatt ttgtagaata aaatgaatta agattgaaga gcc 6713 <![CDATA[<210> 28]]> <![CDATA[<211> 1443]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 28]]> aagtgtgccg gcgtcgcgcg aaggttcagc agggagccgt gggccgggcg cgccggttcc 60 cggcacgtgt ctcggcacgt ggcagcgcgc ctggccctgg gcttggaggc gccggcgccc 120 tggatccgcc ggccgtggtc gccgagtcgg tgtcgtcctt gaccatcgcc gacgcgttca 180 ttgcagccgg cgagagctca gctccgaccc cgccgcgccc cgcgcttccc aggaggttca 240 tctgctcctt ccctgactgc agcgccaatt acagcaaagc ctggaagctt gacgcgcacc 300 tgtgcaagca cacgggggag agaccatttg tttgtgacta tgaagggtgt ggcaaggcct 360 tcatcaggga ctaccatctg agccgccaca ttctgactca cacaggagaa aagccgtttg 420 tttgtgcagc caatggctgt gatcaaaaat tcaacacaaa atcaaacttg aagaaacatt 480 ttgaacgcaa acatgaaaat caacaaaaac aatatatatg cagttttgaa gactgtaaga 540 agacctttaa gaaacatcag cagctgaaaa tccatcagtg ccagcatacc aatgaacctc 600 tattcaagtg tacccaggaa ggatgtggga aacactttgc atcacccagc aagctgaaac 660 gacatgccaa ggcccacgag ggctatgtat gtcaaaaagg atgttccttt gtggcaaaaa 720 catggacgga acttctgaaa catgtgagag aaacccataa agaggaaata ctatgtgaag 780 tatgccggaa aacatttaaa cgcaaagatt accttaagca acacatgaaa actcatgccc 840 cagaaaggga tgtatgtcgc tgtccaagag aaggctgtgg aagaacctat acaactgtgt 900 ttaatctcca aagccatatc ctctccttcc atgaggaaag ccgccctttt gtgtgtgaac 960 atgctggctg tggcaaaaca tttgcaatga aacaaagtct cactaggcat gctgttgtac 1020 atgatcctga caagaagaaa atgaagctca aagtcaaaaa atctcgtgaa aaacggagtt 1080 tggcctctca tctcagtgga tatatccctc ccaaaaggaa acaagggcaa ggcttatctt 1140 tgtgtcaaaa cggagagtca cccaactgtg tggaagacaa gatgctctcg acagttgcag 1200 tacttaccct tggctaagaa ctgcactgct ttgtttaaag gactgcagac caaggagcga 1260 gctttctctc agagcatgct tttctttatt aaaattactg atgcagaaca tttgattcct 1320 tatcatttcc atggtctttg ttcaaagtgt ctctttcctg ggtctcttga gtttctttat 1380 atgccttctc ctcatttttg ctgaaagcac gaagaacaca cattaaagct tttcctcctt 1440 gaa 1443 <![CDATA[<210> 29]]> <![CDATA[<211> 3946]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 29]]> agtgcacagt gctgcctcgt ctgaggggac aggaggatca ccctcttcgt cgcttcggcc 60 agtgtgtcgg gctgggccct gacaagccac ctgaggagag gctcggagcc gggcccggac 120 cccggcgatt gccgcccgct tctctctagt ctcacgaggg gtttcccgcc tcgcaccccc 180 acctctggac ttgcctttcc ttctcttctc cgcgtgtgga gggagccagc gcttaggccg 240 gagcgagcct gggggccgcc cgccgtgaag acatcgcggg gaccgattca ccatggaggg 300 cgccggcggc gcgaacgaca agaaaaagat aagttctgaa cgtcgaaaag aaaagtctcg 360 agatgcagcc agatctcggc gaagtaaaga atctgaagtt ttttatgagc ttgctcatca 420 gttgccactt ccacataatg tgagttcgca tcttgataag gcctctgtga tgaggcttac 480 catcagctat ttgcgtgtga ggaaacttct ggatgctggt gatttggata ttgaagatga 540 catgaaagca cagatgaatt gcttttattt gaaagccttg gatggttttg ttatggttct 600 cacagatgat ggtgacatga tttacatttc tgataatgtg aacaaataca tgggattaac 660 tcagtttgaa ctaactggac acagtgtgtt tgattttact catccatgtg accatgagga 720 aatgagagaa atgcttacac acagaaatgg ccttgtgaaa aagggtaaag aacaaaacac 780 acagcgaagc ttttttctca gaatgaagtg taccctaact agccgaggaa gaactatgaa 840 cataaagtct gcaacatgga aggtattgca ctgcacaggc cacattcacg tatatgatac 900 caacagtaac caacctcagt gtgggtataa gaaaccacct atgacctgct tggtgctgat 960 ttgtgaaccc attcctcacc catcaaatat tgaaattcct ttagatagca agactttcct 1020 cagtcgacac agcctggata tgaaattttc ttattgtgat gaaagaatta ccgaattgat 1080 gggatatgag ccagaagaac ttttaggccg ctcaatttat gaatattatc atgctttgga 1140 ctctgatcat ctgaccaaaa ctcatcatga tatgtttact aaaggacaag tcaccacagg 1200 acagtacagg atgcttgcca aaagaggtgg atatgtctgg gttgaaactc aagcaactgt 1260 catatataac accaagaatt ctcaaccaca gtgcattgta tgtgtgaatt acgttgtgag 1320 tggtattatt cagcacgact tgattttctc ccttcaacaa acagaatgtg tccttaaacc 1380 ggttgaatct tcagatatga aaatgactca gctattcacc aaagttgaat cagaagatac 1440 aagtagcctc tttgacaaac ttaagaagga acctgatgct ttaactttgc tggccccagc 1500 cgctggagac acaatcatat ctttagattt tggcagcaac gacacagaaa ctgatgacca 1560 gcaacttgag gaagtaccat tatataatga tgtaatgctc ccctcaccca acgaaaaatt 1620 acagaatata aatttggcaa tgtctccatt acccaccgct gaaacgccaa agccacttcg 1680 aagtagtgct gaccctgcac tcaatcaaga agttgcatta aaattagaac caaatccaga 1740 gtcactggaa ctttctttta ccatgcccca gattcaggat cagacaccta gtccttccga 1800 tggaagcact agacaaagtt cacctgagcc taatagtccc agtgaatatt gtttttatgt 1860 ggatagtgat atggtcaatg aattcaagtt ggaattggta gaaaaacttt ttgctgaaga 1920 cacagaagca aagaacccat tttctactca ggacacagat ttagacttgg agatgttagc 1980 tccctatatc ccaatggatg atgacttcca gttacgttcc ttcgatcagt tgtcaccatt 2040 agaaagcagt tccgcaagcc ctgaaagcgc aagtcctcaa agcacagtta cagtattcca 2100 gcagactcaa atacaagaac ctactgctaa tgccaccact accactgcca ccactgatga 2160 attaaaaaca gtgacaaaag accgtatgga agacattaaa atattgattg catctccatc 2220 tcctacccac atacataaag aaactactag tgccacatca tcaccatata gagatactca 2280 aagtcggaca gcctcaccaa acagagcagg aaaaggagtc atagaacaga cagaaaaatc 2340 tcatccaaga agccctaacg tgttatctgt cgctttgagt caaagaacta cagttcctga 2400 ggaagaacta aatccaaaga tactagcttt gcagaatgct cagagaaagc gaaaaatgga 2460 acatgatggt tcactttttc aagcagtagg aattggaaca ttattacagc agccagacga 2520 tcatgcagct actacatcac tttcttggaa acgtgtaaaa ggatgcaaat ctagtgaaca 2580 gaatggaatg gagcaaaaga caattatttt aataccctct gatttagcat gtagactgct 2640 ggggcaatca atggatgaaa gtggattacc acagctgacc agttatgatt gtgaagttaa 2700 tgctcctata caaggcagca gaaacctact gcagggtgaa gaattactca gagctttgga 2760 tcaagttaac tgagcttttt cttaatttca ttcctttttt tggacactgg tggctcatta 2820 cctaaagcag tctatttata ttttctacat ctaattttag aagcctggct acaatactgc 2880 acaaacttgg ttagttcaat tttgatcccc tttctactta atttacatta atgctctttt 2940 ttagtatgtt ctttaatgct ggatcacaga cagctcattt tctcagtttt ttggtattta 3000 aaccattgca ttgcagtagc atcattttaa aaaatgcacc tttttattta tttatttttg 3060 gctagggagt ttatcccttt ttcgaattat ttttaagaag atgccaatat aatttttgta 3120 agaaggcagt aacctttcat catgatcata ggcagttgaa aaatttttac accttttttt 3180 tcacatttta cataaataat aatgctttgc cagcagtacg tggtagccac aattgcacaa 3240 tatattttct taaaaaatac cagcagttac tcatggaata tattctgcgt ttataaaact 3300 agtttttaag aagaaatttt ttttggccta tgaaattgtt aaacctggaa catgacattg 3360 ttaatcatat aataatgatt cttaaatgct gtatggttta ttatttaaat gggtaaagcc 3420 atttacataa tatagaaaga tatgcatata tctagaaggt atgtggcatt tatttggata 3480 aaattctcaa ttcagagaaa tcatctgatg tttctatagt cactttgcca gctcaaaaga 3540 aaacaatacc ctatgtagtt gtggaagttt atgctaatat tgtgtaactg atattaaacc 3600 taaatgttct gcctaccctg ttggtataaa gatattttga gcagactgta aacaagaaaa 3660 aaaaaatcat gcattcttag caaaattgcc tagtatgtta atttgctcaa aatacaatgt 3720 ttgattttat gcactttgtc gctattaaca tccttttttt catgtagatt tcaataattg 3780 agtaatttta gaagcattat tttaggaata tatagttgtc acagtaaata tcttgttttt 3840 tctatgtaca ttgtacaaat ttttcattcc ttttgctctt tgtggttgga tctaacacta 3900 actgtattgt tttgttacat caaataaaca tcttctgtgg accagg 3946 <![CDATA[<210> 30]]> <![CDATA[<211> 3257]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 30]]> gctcagagtt gcactgagtg tggctgaagc agcgaggcgg gagtggaggt gcgcggagtc 60 aggcagacag acagacacag ccagccagcc aggtcggcag tatagtccga actgcaaatc 120 ttattttctt ttcaccttct ctctaactgc ccagagctag cgcctgtggc tcccgggctg 180 gtgtttcggg agtgtccaga gagcctggtc tccagccgcc cccgggagga gagccctgct 240 gcccaggcgc tgttgacagc ggcggaaagc agcggtaccc acgcgcccgc cgggggaagt 300 cggcgagcgg ctgcagcagc aaagaacttt cccggctggg aggaccggag acaagtggca 360 gagtcccgga gccaactttt gcaagccttt cctgcgtctt aggcttctcc acggcggtaa 420 agaccagaag gcggcggaga gccacgcaag agaagaagga cgtgcgctca gcttcgctcg 480 caccggttgt tgaacttggg cgagcgcgag ccgcggctgc cgggcgcccc ctccccctag 540 cagcggagga ggggacaagt cgtcggagtc cgggcggcca agacccgccg ccggccggcc 600 actgcagggt ccgcactgat ccgctccgcg gggagagccg ctgctctggg aagtgagttc 660 gcctgcggac tccgaggaac cgctgcgcac gaagagcgct cagtgagtga ccgcgacttt 720 tcaaagccgg gtagcgcgcg cgagtcgaca agtaagagtg cgggaggcat cttaattaac 780 cctgcgctcc ctggagcgag ctggtgagga gggcgcagcg gggacgacag ccagcgggtg 840 cgtgcgctct tagagaaact ttccctgtca aaggctccgg ggggcgcggg tgtcccccgc 900 ttgccacagc cctgttgcgg ccccgaaact tgtgcgcgca gcccaaacta acctcacgtg 960 aagtgacgga ctgttctatg actgcaaaga tggaaacgac cttctatgac gatgccctca 1020 acgcctcgtt cctcccgtcc gagagcggac cttatggcta cagtaacccc aagatcctga 1080 aacagagcat gaccctgaac ctggccgacc cagtggggag cctgaagccg cacctccgcg 1140 ccaagaactc ggacctcctc acctcgcccg acgtggggct gctcaagctg gcgtcgcccg 1200 agctggagcg cctgataatc cagtccagca acgggcacat caccaccacg ccgaccccca 1260 cccagttcct gtgccccaag aacgtgacag atgagcagga gggcttcgcc gagggcttcg 1320 tgcgcgccct ggccgaactg cacagccaga acacgctgcc cagcgtcacg tcggcggcgc 1380 agccggtcaa cggggcaggc atggtggctc ccgcggtagc ctcggtggca gggggcagcg 1440 gcagcggcgg cttcagcgcc agcctgcaca gcgagccgcc ggtctacgca aacctcagca 1500 acttcaaccc aggcgcgctg agcagcggcg gcggggcgcc ctcctacggc gcggccggcc 1560 tggcctttcc cgcgcaaccc cagcagcagc agcagccgcc gcaccacctg ccccagcaga 1620 tgcccgtgca gcacccgcgg ctgcaggccc tgaaggagga gcctcagaca gtgcccgaga 1680 tgcccggcga gacaccgccc ctgtccccca tcgacatgga gtcccaggag cggatcaagg 1740 cggagaggaa gcgcatgagg aaccgcatcg ctgcctccaa gtgccgaaaa aggaagctgg 1800 agagaatcgc ccggctggag gaaaaagtga aaaccttgaa agctcagaac tcggagctgg 1860 cgtccacggc caacatgctc agggaacagg tggcacagct taaacagaaa gtcatgaacc 1920 acgttaacag tgggtgccaa ctcatgctaa cgcagcagtt gcaaacattt tgaagagaga 1980 ccgtcggggg ctgaggggca acgaagaaaa aaaataacac agagagacag acttgagaac 2040 ttgacaagtt gcgacggaga gaaaaaagaa gtgtccgaga actaaagcca agggtatcca 2100 agttggactg ggttgcgtcc tgacggcgcc cccagtgtgc acgagtggga aggacttggc 2160 gcgccctccc ttggcgtgga gccagggagc ggccgcctgc gggctgcccc gctttgcgga 2220 cgggctgtcc ccgcgcgaac ggaacgttgg acttttcgtt aacattgacc aagaactgca 2280 tggacctaac attcgatctc attcagtatt aaagggggga gggggagggg gttacaaact 2340 gcaatagaga ctgtagattg cttctgtagt actccttaag aacacaaagc ggggggaggg 2400 ttggggaggg gcggcaggag ggaggtttgt gagagcgagg ctgagcctac agatgaactc 2460 tttctggcct gccttcgtta actgtgtatg tacatatata tattttttaa tttgatgaaa 2520 gctgattact gtcaataaac agcttcatgc ctttgtaagt tatttcttgt ttgtttgttt 2580 gggtatcctg cccagtgttg tttgtaaata agagatttgg agcactctga gtttaccatt 2640 tgtaataaag tatataattt ttttatgttt tgtttctgaa aattccagaa aggatattta 2700 agaaaataca ataaactatt ggaaagtact cccctaacct cttttctgca tcatctgtag 2760 atactagcta tctaggtgga gttgaaagag ttaagaatgt cgattaaaat cactctcagt 2820 gcttcttact attaagcagt aaaaactgtt ctctattaga ctttagaaat aaatgtacct 2880 gatgtacctg atgctatggt caggttatac tcctcctccc ccagctatct atatggaatt 2940 gcttaccaaa ggatagtgcg atgtttcagg aggctggagg aaggggggtt gcagtggaga 3000 gggacagccc actgagaagt caaacatttc aaagtttgga ttgtatcaag tggcatgtgc 3060 tgtgaccatt tataatgtta gtagaaattt tacaataggt gcttattctc aaagcaggaa 3120 ttggtggcag attttacaaa agatgtatcc ttccaatttg gaatcttctc tttgacaatt 3180 cctagataaa aagatggcct ttgcttatga atatttataa cagcattctt gtcacaataa 3240 atgtattcaa ataccaa 3257 <![CDATA[<210> 31]]> <![CDATA[<211> 1830]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 31]]> gggaccttga gagcggccag gccagcctcg gagccagcag ggagctggga gctgggggaa 60 acgacgccag gaaagctatc gcgccagaga gggcgacggg ggctcgggaa gcctgacagg 120 gcttttgcgc acagctgccg gctggctgct acccgcccgc gccagccccc gagaacgcgc 180 gaccaggcac ccagtccggt caccgcagcg gagagctcgc cgctcgctgc agcgaggccc 240 ggagcggccc cgcagggacc ctccccagac cgcctgggcc gcccggatgt gcactaaaat 300 ggaacagccc ttctaccacg acgactcata cacagctacg ggatacggcc gggcccctgg 360 tggcctctct ctacacgact acaaactcct gaaaccgagc ctggcggtca acctggccga 420 cccctaccgg agtctcaaag cgcctggggc tcgcggaccc ggcccagagg gcggcggtgg 480 cggcagctac ttttctggtc agggctcgga caccggcgcg tctctcaagc tcgcctcttc 540 ggagctggaa cgcctgattg tccccaacag caacggcgtg atcacgacga cgcctacacc 600 cccgggacag tacttttacc cccgcggggg tggcagcggt ggaggtgcag ggggcgcagg 660 gggcggcgtc accgaggagc aggagggctt cgccgacggc tttgtcaaag ccctggacga 720 tctgcacaag atgaaccacg tgacaccccc caacgtgtcc ctgggcgcta ccggggggcc 780 cccggctggg cccgggggcg tctacgccgg cccggagcca cctcccgttt acaccaacct 840 cagcagctac tccccagcct ctgcgtcctc gggaggcgcc ggggctgccg tcgggaccgg 900 gagctcgtac ccgacgacca ccatcagcta cctcccacac gcgccgccct tcgccggtgg 960 ccacccggcg cagctgggct tgggccgcgg cgcctccacc ttcaaggagg aaccgcagac 1020 cgtgccggag gcgcgcagcc gggacgccac gccgccggtg tcccccatca acatggaaga 1080 ccaagagcgc atcaaagtgg agcgcaagcg gctgcggaac cggctggcgg ccaccaagtg 1140 ccggaagcgg aagctggagc gcatcgcgcg cctggaggac aaggtgaaga cgctcaaggc 1200 cgagaacgcg gggctgtcga gtaccgccgg cctcctccgg gagcaggtgg cccagctcaa 1260 acagaaggtc atgacccacg tcagcaacgg ctgtcagctg ctgcttgggg tcaagggaca 1320 cgccttctga acgtcccctg cccctttacg gacaccccct cgcttggacg gctgggcaca 1380 cgcctcccac tggggtccag ggagcaggcg gtgggcaccc accctgggac ctaggggcgc 1440 cgcaaaccac actggactcc ggccctccta ccctgcgccc agtccttcca cctcgacgtt 1500 tacaagcccc cccttccact tttttttgta tgtttttttt ctgctggaaa cagactcgat 1560 tcatattgaa tataatatat ttgtgtattt aacagggagg ggaagagggg gcgatcgcgg 1620 cggagctggc cccgccgcct ggtactcaag cccgcgggga cattgggaag gggacccccg 1680 ccccctgccc tcccctctct gcaccgtact gtggaaaaga aacacgcact tagtctctaa 1740 agagtttatt ttaagacgtg tttgtgtttg tgtgtgtttg ttctttttat tgaatctatt 1800 taagtaaaaa aaaaattggt tctttattaa 1830 <![CDATA[<210> 32]]> <![CDATA[<211> 1929]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 32]]> aggagccgcc gccagtggag ggccgggcgc tgcggccgcg gccggggcgg gcgcagggcc 60 gagcggacgg gggggcgcgg gccccccggg aggccgcggc cactcccccc cgggccggcg 120 cggcggggga ggcggaggat ggaaacaccc ttctacggcg atgaggcgct gagcggcctg 180 ggcggcggcg ccagtggcag cggcggcagc ttcgcgtccc cgggccgctt gttccccggg 240 gcgcccccga cggccgcggc cggcagcatg atgaagaagg acgcgctgac gctgagcctg 300 agtgagcagg tggcggcagc gctcaagcct gcggccgcgc cgcctcctac ccccctgcgc 360 gccgacggcg cccccagcgc ggcacccccc gacggcctgc tcgcctctcc cgacctgggg 420 ctgctgaagc tggcctcccc cgagctcgag cgcctcatca tccagtccaa cgggctggtc 480 accaccacgc cgacgagctc acagttcctc taccccaagg tggcggccag cgaggagcag 540 gagttcgccg agggcttcgt caaggccctg gaggatttac acaagcagaa ccagctcggc 600 gcgggcgcgg ccgctgccgc cgccgccgcc gccgccgggg ggccctcggg cacggccacg 660 ggctccgcgc cccccggcga gctggccccg gcggcggccg cgcccgaagc gcctgtctac 720 gcgaacctga gcagctacgc gggcggcgcc gggggcgcgg ggggcgccgc gacggtcgcc 780 ttcgctgccg aacctgtgcc cttcccgccg ccgccacccc caggcgcgtt ggggccgccg 840 cgcctggctg cgctcaagga cgagccacag acggtgcccg acgtgccgag cttcggcgag 900 agcccgccgt tgtcgcccat cgacatggac acgcaggagc gcatcaaggc ggagcgcaag 960 cggctgcgca accgcatcgc cgcctccaag tgccgcaagc gcaagctgga gcgcatctcg 1020 cgcctggaag agaaagtgaa gaccctcaag agtcagaaca cggagctggc gtccacggcg 1080 agcctgctgc gcgagcaggt ggcgcagctc aagcagaaag tcctcagcca cgtcaacagc 1140 ggctgccagc tgctgcccca gcaccaggtg cccgcgtact gagtccgcgc gcggggcgca 1200 tgcgcggcca ccctccccaa ggggcgggct cgcggggggg tgtcgtgggc gccccggact 1260 tggagagggt gcggccctgg ggaccccccc tccccgagtg tgcccaggaa ctcagagagg 1320 gcgcggcccc cggggattcc ccccccccga gggtgcccag gactcgacaa gctggacccc 1380 ctgctcccgg gggggcgagc gcatgacccc cccgccctcg cgctgcctct ttcccccgcg 1440 cggccgcccc gtgttgcaca aacccgcgcg tctcggctgc ccctttgtac accgcgccgc 1500 ggaagggggc tccgaggggg cgcagcctca aaccctgcct ttcctttact tttacttttt 1560 tttttttttc tttggaagag agaagaacag agtgttcgat tctgccctat ttatgtttct 1620 actcgggaac aaacgttggt tgtgtgtgtg tgtgttttct tgtgttggtt ttttaaagaa 1680 atgggaagaa gaaaaaaaaa ttctccgccc ctttcctcga tctcgctccc cccttcggtt 1740 ctttcgaccg gtcccccctc ccttttttgt tctgttttgt tttgttttgc tacgagtcca 1800 cattcctgtt tgtaatcctt ggttcgcccg gttttctgtt ttcagtaaag tctcgttacg 1860 ccagctcggc tctccgcctc cttcttcccc cgccggggcc tggcgggctg ggcggggcct 1920 ggttcgctt 1929 <![CDATA[<210> 33]]> <![CDATA[<211> 2915]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 33]]> gcagacggcg ctgagcgcgg cggcggcggg agcggcgtcg agtgtctccg tgcgcccgtc 60 tgtggccaag cagccagcag cctagcagcc agtcagcttg ccgccggcgg ccaagcagcc 120 aaccatgctc aacttcggtg cctctctcca gcagactgcg gaggaaagaa tggaaatgat 180 ttctgaaagg ccaaaagaga gtatgtattc ctggaacaaa actgcagaga aaagtgattt 240 tgaagctgta gaagcactta tgtcaatgag ctgcagttgg aagtctgatt ttaagaaata 300 cgttgaaaac agacctgtta caccagtatc tgatttgtca gaggaagaga atctgcttcc 360 gggaacacct gattttcata caatcccagc attttgtttg actccacctt acagtccttc 420 tgactttgaa ccctctcaag tgtcaaatct gatggcacca gcgccatcta ctgtacactt 480 caagtcactc tcagatactg ccaaacctca cattgccgca cctttcaaag aggaagaaaa 540 gagcccagta tctgccccca aactccccaa agctcaggca acaagtgtga ttcgtcatac 600 agctgatgcc cagctatgta accaccagac ctgcccaatg aaagcagcca gcatcctcaa 660 ctatcagaac aattctttta gaagaagaac ccacctaaat gttgaggctg caagaaagaa 720 cataccatgt gccgctgtgt caccaaacag atccaaatgt gagagaaaca cagtggcaga 780 tgttgatgag aaagcaagtg ctgcacttta tgacttttct gtgccttcct cagagacggt 840 catctgcagg tctcagccag cccctgtgtc cccacaacag aagtcagtgt tggtctctcc 900 acctgcagta tctgcagggg gagtgccacc tatgccggtc atctgccaga tggttcccct 960 tcctgccaac aaccctgttg tgacaacagt cgttcccagc actcctccca gccagccacc 1020 agccgtttgc ccccctgttg tgttcatggg cacacaagtc cccaaaggcg ctgtcatgtt 1080 tgtggtaccc cagcccgttg tgcagagttc aaagcctccg gtggtgagcc cgaatggcac 1140 cagactctct cccattgccc ctgctcctgg gttttcccct tcagcagcaa aagtcactcc 1200 tcagattgat tcatcaagga taaggagtca catctgtagc cacccaggat gtggcaagac 1260 atactttaaa agttcccatc tgaaggccca cacgaggacg cacacaggag aaaagccttt 1320 cagctgtagc tggaaaggtt gtgaaaggag gtttgcccgt tctgatgaac tgtccagaca 1380 caggcgaacc cacacgggtg agaagaaatt tgcgtgcccc atgtgtgacc ggcggttcat 1440 gaggagtgac catttgacca agcatgcccg gcgccatcta tcagccaaga agctaccaaa 1500 ctggcagatg gaagtgagca agctaaatga cattgctcta cctccaaccc ctgctcccac 1560 acagtgacag accggaaagt gaagagtcag aactaacttt ggtctcagcg ggagccagtg 1620 gtgatgtaaa aatgcttcca ctgcaagtct gtggccccac aacgtgggct taaagcagaa 1680 gccccacagc ctggcacgaa ggccccgcct gggttaggtg actaaaaggg cttcggccac 1740 aggcaggtca cagaaaggca ggtttcattt cttatcacat aagagagatg agaaagcttt 1800 tattcctttg aatatttttt gaaggtttca gatgaggtca acacaggtag cacagatttt 1860 gaatctgtgt gcatatttgt tactttactt ttgctgttta tacttgagac caacttttca 1920 atgtgattct tctaaagcac tggtttcaag aatatggagg ctggaaggaa ataaacatta 1980 cggtacagac atggagatgt aaaatgagtt tgtattatta caaatattgt catctttttc 2040 tagagttatc ttctttatta ttcctagtct ttccagtcaa catcgtggat gtagtgatta 2100 aatatatcta gaactatcat ttttacacta ttgtgaatat ttggaattga acgactgtat 2160 attgctaaga gggcccaaag aattggaatc ctccttaatt taattgcttt gaagcatagc 2220 tacaatttgt ttttgcattt ttgttttgaa agtttaacaa atgactgtat ctaggcattt 2280 cattatgctt tgaactttag tttgcctgca gtttcttgtg tagatttgaa aattgtatac 2340 caatgtgttt tctgtagact ctaagataca ctgcactttg tttagaaaaa aaactgaaga 2400 tgaaatatat attgtaaaga agggatatta agaatcttag ataacttctt gaaaaagatg 2460 gcttatgtca tcagtaaagt acctttatgt tatgaggata taatgtgtgc tttattgaat 2520 tagaaaatta gtgaccatta ttcacaggtg gacaaatgtt gatgttgtcc tgttaattta 2580 taggcgtttt ttggggatgt ggaggtagtt gggtagaaaa attattagaa cattcacttt 2640 tgttaacagt atttctcttt tattctgtta tatagtggat gatatacaca gtggcaaaac 2700 aaaagtacat tgcttaaaat atatagtgaa aaatgtcact atatcttccc atttaacatt 2760 gtttttgtat attgggtgta gatttctgac atcaaaactt ggacccttgg aaaacaaaag 2820 ttttaattaa aaaaaatcct tgtgacttac aatttgcaca atatttcttt tgttgtactt 2880 tatatcttgt ttacaataaa gaattccctt tggta 2915 <![CDATA[<210> 34]]> <![CDATA[<211> 5201]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 34]]> cttactcatt tgtgtttatt cttggactta tcctgacata atggggtttt tttaattata 60 gattcacact gcatttattc atcacccctg tcctctcatc cataactcaa atttactacc 120 agcaacacaa aatacaaaga tgtgtccagt ttcactacag ctcttcgcgt ttacaagtgt 180 cgagcgcttg ctttcggaac gcccttgtga ttggccgagc caatgccagt gacatcaacc 240 aacttacttt tgattggaag gctggttgct gggactgtag cgtttgcagg aagtcactta 300 actgtttggg agctggaaaa ccgaagctga agttctcttt tgccatagga acgagcgcaa 360 ctgactagga aagatgtgtc ccaaagctcc gcaagctgga acgtgagcca ggaggcccgg 420 accggccacg ggaccgcgag gcactccgaa agtgtgcggc tgccccttcc ctgcctccca 480 gctgttaccc ttttaaatgt cagtgttcga ggctgtaggg gtagcacgag gcagcgaaac 540 ggaacagtcg gattggccgc acgcctcagt tctagacgca cctctccacc gaaggccgtt 600 ctgactggca gggggagaaa gtaaacagag ttgaatcacc ctccccactg gccaattgga 660 gggggtttgg tttgtgacgt gatgggattc tgcgaaattg ttactgagca agagaatgcc 720 ggaacggtgc ggaccggccg gagcaggggt tcagaagccg tcagtggact cgggaaaaag 780 tgtctcttag acctggcgct cggcgggacc ctcgccaccc gcgtcggggt gatcgggtga 840 atgtcctggg gctttggctc gacggcgagg cggccgaggg cgtgcacctc tcttgcagtt 900 tcctctccca gcgcctcggg ggcgttttca gtcgaataaa cttgcgaccg ccacgtgtgg 960 catctttcca agggagccgg ctcagagggg ccggcgcgcc cgtcggggga tcgcggccgg 1020 cgcggggcag gggcggcggc tagaggcggc ggcgcggcgg agcccggggc cgtggatgct 1080 gcgtgcggag gcgctgccgg ttacgtaaag atgaggggct gaggtcgcct cggcgctcct 1140 gcgagtcgga agcgccccgc gcccccgccc ccttggccgc cgcgccgtgc cgcgccgcgc 1200 cgcgctcgtc gtccgaggcc agggcagggc gagccgaacc tccgcagcca ccgccaagtt 1260 tgtccgcgcc gcctgggctg ccgtcgcccg caccatgtcc gcggccgcct acatggactt 1320 cgtggctgcc cagtgtctgg tttccatttc gaaccgcgct gcggtgccgg agcatggggt 1380 cgctccggac gccgagcggc tgcgactacc tgagcgcgag gtgaccaagg agcacggtga 1440 cccgggggac acctggaagg attactgcac actggtcacc atcgccaaga gcttgttgga 1500 cctgaacaag taccgaccca tccagacccc ctccgtgtgc agcgacagtc tggaaagtcc 1560 agatgaggat atgggatccg acagcgacgt gaccaccgaa tctgggtcga gtccttccca 1620 cagcccggag gagagacagg atcctggcag cgcgcccagc ccgctctccc tcctccatcc 1680 tggagtggct gcgaagggga aacacgcctc cgaaaagagg cacaagtgcc cctacagtgg 1740 ctgtgggaaa gtctatggaa aatcctccca tctcaaagcc cattacagag tgcatacagg 1800 tgaacggccc tttccctgca cgtggccaga ctgccttaaa aagttctccc gctcagacga 1860 gctgacccgc cactaccgga cccacactgg ggaaaagcag ttccgctgtc cgctgtgtga 1920 gaagcgcttc atgaggagtg accacctcac aaagcacgcc cggcggcaca ccgagttcca 1980 ccccagcatg atcaagcgat cgaaaaaggc gctggccaac gctttgtgag gtgctgcccg 2040 tggaagccag ggagggatgg accccgaaag gagaaaagta ctcccaggaa acagacgcgt 2100 gaaaactgag ccccagaaga ggcacacttg acggcacagg aagtcactgc tctttggtca 2160 atattctgat tttcctctcc ctgcattgtt tttaaaaagc acattgtagc ctaagatcaa 2220 agtcaacaac actcggtccc cttgaagagg caactctctg aacccgtctc tgactgttgg 2280 agggaaggca aatgcttttg ggttttttgg tttttgtttt tgtttttttt tctcctttta 2340 tttttttgcg ggggagggta gggagtgggt gggggggagg ggggtaaggc caagactggg 2400 gtagaatttt aaagattcaa cactggtgta catatgtccg ctgggtgagt tgacctgtgg 2460 cctcgcacag tgattctggg ccctttatgc ttgctgtctc tcagaattgt tttcttacct 2520 tttaatgtaa tgacgagtgt gcttcagttt gtttagcaaa accactctct tgaatcacgt 2580 taacttttga gattaaaaaa aaaaacgcca tagcacagct gtctttatgc aagcaagagc 2640 acatctactc cagcatgatc tgtcatctaa agacttgaaa acaaaaaaca gttacttata 2700 gtcaatgggt aagcagagtc tgaatttata ctaatcaaga caaacctttg aaaggttaca 2760 ctaagtacag aacttttaaa ccttgctttg tatgagttgt actttttgaa cataagctgc 2820 acttttattt tctaatgcag aggatgaata agttaaatac atgctttgag gatagaagca 2880 gatgttctgt ttggcaccac gttataatct gcttatttta caatatacac gtttccctaa 2940 gaaatcatgg cagagatgtg agggcagaat atacacaaca gatgctgaag gagaaggagg 3000 gtagtgtttt gcaaaagaaa aagaaaagaa ccaacagaat tttaactcta ttaacttttc 3060 caaattttcc tatgctttta gttaacatca ttattgtatc ctaatgccac taggggagag 3120 agcttttgac tctgttgggt tttatttgaa tgtgtgcata acagtaatga gatctggaaa 3180 cacctatttt ttggggaaaa aggtttgttg gtctccttcc tgtgttccta caaaactccc 3240 actctcaggt gcaagagtta tgtagaagga aagggagctg aaataggaac agaaaaatca 3300 acccctataa ctagtgaaca ccaagggaaa ataccacaat gatttcagag gagactctgc 3360 aaaatcgtcc cttgtggaga atgcaggcaa catggaatac taggaatgaa atcacatcac 3420 tgtatctttt acatcaatag cctcaccact aatatatctt gtatctaggt gtctataatg 3480 gctgaaacca ctacatccat ctatgccatt tacctgaaaa cttaactgtg gcctttatga 3540 ggccagaaaa gtgaactgag ttttcgtagt taagacctca aatgagggga gtcagcagtg 3600 atcatggggg aaatgtttac attttttttt tcttcagaag taacgctttc tgatgatttt 3660 atctgatatt taaaacaggg agctatggtg cactctagtt tatacttgcg ctctgaaatg 3720 tgtaaacata gggtgcctac ctatttcacc tgacccatac tcgtttctga ttcagaatca 3780 gtgtgggctc ctgcagtggg cgcgggtcac ggctgactcc aacttccaat acaacagcca 3840 tcactagcac agtgtttttt tgtttaacca acgtagttgt attagtagtt ctataaagag 3900 aactgctttt aacattaggg actgggagca gtccatggga taaaaaggaa agtgttttct 3960 cacgagaaaa catgtcagga aaaataaaga acactttcta cctctgtttc agatttttga 4020 aacacttatt ttaaaccaaa ttttaatttc tgtgtccaaa ataagtttta aggacatctg 4080 ttcttccata cgaaataggt taggctgcct atttctcact gagctcatgg aatggttctg 4140 cttatgatac tctgcacgct gccttttagt gagtgaggag tttggggttg cctagcaact 4200 tgctaacttg taaaaagtca tctttccctc acagaaagaa acgaaagaaa gcaaagcaaa 4260 gtcagtgaaa gacaatcttt atagtttcag gagtaaatct aaatgtggct tttgtcaagc 4320 acttagatgg atataaatgc agcaacttgt tttaaaaaaa tgcacaattt acttcccaaa 4380 aaagttgtta cttgcctttt caagttgttg acaaacacac atttgatatt ctcttatatg 4440 ttatagtaat gtaacgtata aactcaagcc tttttattct ttgtgattaa atcctgtttt 4500 aaaatgtcac aaaacaggaa ccagcattct aattagattt actatatcaa gatatggttc 4560 aaataggact actagagttc attgaacact aaaactatga aacaattact ttttatatta 4620 aaaagaccat ggatttaact tatgaaaatc caaatgcagg atagtaattt ttgtttactt 4680 ttttaaccaa actgaatttt tgaaagacta ttgcaggtgt ttaaaaagaa agaaaagttg 4740 ttttatctaa tactgtaagt agttgtcata ttctggaaaa tttaatagtt ttagagttaa 4800 gatatctcct ctctttggtt agggaagaag aaagcccttc accattgtgg aatgatgccc 4860 tggctttaag gtttagctcc acatcatgct tctcttgaga attctatttg gtagttacaa 4920 ttacagaaac tgattagttt gtcagtttgc agatagattt agcacagtac tcatcactcg 4980 gatagattga gatgttcttt cacatcagat gatctgtaac actgtaagat actgatcttt 5040 acaactgttt aatcagtttt atttttgtac agtattagtg acctaagtta ttttgctgtc 5100 ccgtttttgt aaatcaaatg aaattataaa agaggattct gacagtaggt attttgtaca 5160 tatgtatata tgttgtccaa ataaaaataa taaatgataa a 5201 <![CDATA[<210> 35]]> <![CDATA[<211> 5582]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 35]]> gggtgggcgg agcgggcccc ccgagcgggg gctggcgagc gcggggaggg ggccgaaagg 60 gcggcaaagc cggcgcgcgc ccggctgggg gcggagggcg ggggcccgcg ggccggaaca 120 gccgcggcaa gtggcggcgg cggcagcggc agcggaggca gctgaggcgg cggcggcgag 180 tgggggtccg ggcggcggcg gcgggcccgg cggcgggccg aggagccggg cgcaatggag 240 cggaagagcc cgagcgggaa gaagttccgc agcaagccgc agctggcgcg ctacctgggc 300 ggctccatgg acctgagcac cttcgacttc cgcacgggca agatgctgat gagcaagatg 360 aacaagagcc gccagcgcgt gcgctacgac tcctccaacc aggtcaaggg caagcccgac 420 ctgaacacgg cgctgcccgt gcgccagacg gcgtccatct tcaagcagcc ggtgaccaag 480 attaccaacc accccagcaa caaggtcaag agcgacccgc agaaggcggt ggaccagccg 540 cgccagctct tctgggagaa gaagctgagc ggcctgaacg ccttcgacat tgctgaggag 600 ctggtcaaga ccatggacct ccccaagggc ctgcaggggg tgggacctgg ctgcacggat 660 gagacgctgc tgtcggccat cgccagcgcc ctgcacacta gcaccatgcc catcacggga 720 cagctctcgg ccgccgtgga gaagaacccc ggcgtatggc tcaacaccac gcagcccctg 780 tgcaaagcct tcatggtgac cgacgaggac atcaggaagc aggaagagct ggtgcagcag 840 gtgcggaagc ggctggagga ggcgctgatg gccgacatgc tggcgcacgt ggaggagctg 900 gcccgtgacg gggaggcgcc gctggacaag gcctgcgctg aggacgacga cgaggaagac 960 gaggaggagg aggaggagga gcccgacccg gacccggaga tggagcacgt ctagggcaga 1020 ggccctgccg agagcccgtg ctgcctgctg gagccgcctg cagacgcggt cctcggcccc 1080 acgtgaacca ggctcggcgg cgaagcccag ccttggagac acccaggagg aaggccgtgc 1140 tcctggctcc ctcctcggcc cgtccccact tcccggggcc tcggggcaca cagctggggc 1200 tgcccccacc cgaaagaccc tccacgctcg tcctctacag agtccggctt cgggaagtgc 1260 cgggtgctcc tgggccctgc ctggctccct acgacctttg ggctcgaggc cagctcctcc 1320 ccatgcccgc tgtcccagct ccttgagact ggagagcagc cagcaggtgc ccggcagctc 1380 ggcgccacgg cttgctgaca gctgggaggg tttctcggtc tggaggcgta gttttgaaac 1440 tcacatcacc cactgtgcag cgtgaggacg ggactctggt ctgctgtggg gggcatgcag 1500 gacggcgcca ctctctgccc tgccatgcgg ctggtggtgc cacagagcct caccgtgcct 1560 gagtggcatg cccaggaggc cgctctcctt cagtaaatgt aacacagtcg aggcacgtca 1620 tcgggcagcc ttccctgtgt gccaacgcca gccttcgctt ctgaaaacca aactccagcc 1680 gctgccagtc gggacttggt cgcccggcgc tgccagaatg ctccactgcc agccggcccc 1740 cctgcctcgg tttcccttct gtttagtggc gacacaggca cccagctttg gggtggtgct 1800 gacgctccca ggggtgccag gagccactgg gacagggtga ggctcccaga cgctcctcga 1860 ggtgcccagc tctccaggga gcttctggcc caaggccgtc tgagggatct gctccttaac 1920 cccccagtgc cttggcgagg gcaggttcca agccacagac gcctgccccg agtggactct 1980 gcggccagtc cctggtgccc tcctggccct gctgcccagt gagggctcct acgggtgggt 2040 tcattggcct gggcccagcg agcccccacc tgcattgacc ttaggcccat agagagggcc 2100 tgtcccggtg ctgccccagc caggatctgg tcgctgcccc agggggactg atgggcagag 2160 tcgcccctgt ggctggactg tgaccatccc tgatggggcc tgaccgcggg agctgaggaa 2220 gcgccgctcc accgtctgcc ctccaaggac ccgcatggag gcagtgggct ggcagcttcc 2280 tgctgctccc tgtcagagtc aaagcacaaa tcctcaggac gggctcaagg gccagggcag 2340 ccgagggaag ctccaggtgg ggaccacgtc ttcctgaggt tggtgcccac tggctgggac 2400 cctttgcagt ggggtggcct cccctctgtc tgcctggtgg agggagccgt gggcgtgggg 2460 acgtgactga ataaagccac catgggtgga tgtgcttgga gcctggagtt cggtgcgtcc 2520 gctagacttt ggtgcccacg tttgagcttc tgtctttggt tgggtgatga aaggctgaaa 2580 gcggtgtggg gacagggcca gcaggtcccc caacctcgcg gacattcaca acccaagagt 2640 caggcttagg ggtattcaga gaagaccagg ccggcctggg catctgtggg caagggccgt 2700 gccccctgag gtgccgctgg ctcagcctag ggatcgtggg tcttggccct gctgccccgg 2760 tgaggaagat gggctggggc tcagacccag caccgctcct tccaaaggaa gggaagcagg 2820 aggggctgcc tggcagggag ggccccccag gtcctcaggt cctgcacagc cgctgcaggg 2880 aggggagctg tgccccggga ccctggactt cagctcacta gccatggcca ctggaagctg 2940 ctttctggac ctgaaggctg ggaggccacc ctcccctcat ctgcccggca ctcagagaca 3000 ctctgtttcc ctcttcccat ctcccactgt gtccctgtct cccttggtct ctctctgtct 3060 ctgtctatcc ctgtctctat ctctccctct tgtctctctc ttgcgccgtc tccctctctg 3120 tccctctttg tttcttgctc tctctcctgt ctctctccct cggtctctgt ctctgtctct 3180 tgctgtctct ccctctctgt cgcagcccag cttcctgtca ctgacagacc ccgatcagtc 3240 cctctgatcc cggggttctg gccatgtcct ggccttggtc tgagatgtga tgatccctac 3300 ccctgccaca gggccctccc cactggaagc ccatccaggc cctgggctgt cgctgttgac 3360 gaagcttgag ggtcctttcc tctctccctg aaaccttggg gacccccaca ggccaaggca 3420 atactggcct ttgctagagg tcgtgcccgg tgagaagtga gttgtaggcg tgggcacctg 3480 aggggccagc ccagtgctca ggccctcgtc aaattccctg ccctggaaaa gtctcagacc 3540 ctcaggctga accccctggg cgcaccgagg ctccacactc cagccccaga acccagacct 3600 ggcatggggc ggggaagcct gagctcccaa tgctgggatc tttcgtgggg gcctcatgac 3660 cagcctgccc tgtgcggtgc ctggccccat cctcaaaggc cacttggctg cccccagccc 3720 cgcccatgtc tcagccccaa gaccttctgg gacttttttt ttttttagac aagagtttcg 3780 ctcttctttc gctcttgttg cacaggctgg agtgcagtgg cgtgatctgg gctcactgca 3840 acctccacct tctgggttca agcctcagcc tcccgagtag ccaccacgcc cagctaattt 3900 ttgtattttt aatagagaca gggtttcacc atgttggcca gtctggtctg gaactcctaa 3960 cctcaggtga tccgcccgcc ccagcttccc aaattgccgg gattacaggt gtgaaccacc 4020 atggcagccc ttctggcact tgccagcagc agcaagagcc tcacgtgtcc cccgcctccc 4080 ctcagaccaa gctccccacc gctgccgcca cagagggtac cagggaggag aggctcagga 4140 cccccgtggc gaggatgcac ctcccagccc tcggcccagc cacacggacc acagggctcc 4200 cgagtctcag caacaccagc taaggggcat catgcctctc ctgccacacc cagggcccgt 4260 gccttgctgt ccctgcagcc cccagaccca ggcagacagg gacagccctt ctgaccaccg 4320 cacacactcg ccaccgcaaa gatccccggg gatgcccctc gcctgtgtgt gtccctcatg 4380 gctgtcacag caaatctcca ggagcccgga ggtgcccatg gaaaacaccc ccagcttccg 4440 gaacgttctt tcggacaggg ccataccgga gcaagactca gctttctggt agcgggtggc 4500 tgggcactgc ctgtgagatt ctgtcacact cgctccagat tcaaggggtc caaaaagtgt 4560 aaacaagtca agtgcccatc cagggatgaa cgaacacagc ccggcccggc cacaccatgg 4620 agcaggactc ggccatgaac aggaaccagg ctctgacacc ggccacggcg cagatgcccc 4680 tggaggagtc caccctcagc aagagacaca cagacaccga cacggcgtgc aatcccattt 4740 gtgtgaatgt ccaggacagg ccgattcaga gacaggaagg ggacacgtgg gtgccagtga 4800 ctggggatta tggggactgg gggaaatggc taaagggcac ccacaaaagt taatgataat 4860 gttccacagt tttttttttg agatggagtc tcactcttgt cacccaggct ggagtgcaat 4920 ggtgtgatct ctgctcactg caagctctgc ctcctgggtt cacgccattc tccctcctca 4980 gcctcccaag tagctgagat tacaggcata tgccaccacc cccagtagag acggggtttc 5040 accatgttag ccaggctggt cacgaactcc tgacctcaag tgatccccca cctcggcctc 5100 ccaaagtgct gggattacag gcatgagcca ccgtgcctca ccagaattgt gtactttttt 5160 ttcttcttct tcttcggcat ggagtttcgc tcttgttgcc caggctggag tgcaatggtg 5220 caaacttggc tcaccgcaac ctcctcctcc cgggttcaat agattctcca gcctcagcct 5280 gctgagtagc tgagattacg ggcgcccgcc accacaccca gctaatcttt gtacttttag 5340 tagagacagg gtttcaccat gttggccacg ggcaaaagaa ttttgttgag ggcaaataat 5400 atgagaccac aaaactgcct tccctgctca gttttaattt tcacagtttt aatttttagc 5460 cttctctggt taccaaaata accacgctca cggccgttca tttgaagata tttccagtta 5520 acgtgtgtga agtgggtttt ttgagatgta atttacaagc aataaaatgc tcctgtctct 5580 gc 5582 <![CDATA[<210> 36]]> <![CDATA[<211> 4839]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 36]]> aagcggaggc tccgagctct aggccggccg gcggtggcgg cggcgaggcc gggactcggg 60 cttagggcct gctgtggagg cagcggcgga cgccgagcta agcagtttct ctggaaaccc 120 ccctggtaag tgtggaggag gcgggacact ctgacccaag acgaaaggcc tgtagctcca 180 gccaaagaaa ataaacctta ggagggagaa ggaaaaaaaa aatccatcag ctgttcctga 240 gaacagcctg cattggaatc tacagagagg acaactaatg tgagtgagga agtgactgta 300 tgtggactgt ggagaaagta agtcacgtgg gcccttgagg acctggactg ggttaggaac 360 agttgtactt tcagaggtga ggtgtcgaga agggaaagtg aatgtggtct ggagtgtgtc 420 cttggccttg gctccacagg gtgtgctttc ctctggggcc gtcagggagc tcatcccttg 480 tgttctgcca gggtggggta cggggtttga cactgaggag ggtaacctgc tggctggagc 540 ggcagagcag tggccttgat ttgtcttttg gaagatttta aaaaccaaaa agcataaaca 600 ttctggtcct tcagcaatgc tttctctgaa gaaatactta acggaaggac ttctccagtt 660 caccattctg ctgagtttga ttggggtacg ggtggacgtg gatacttacc tgacctcaca 720 gcttccccca ctccgggaga tcatcctggg gcccagttct gcctatactc agacccagtt 780 ccacaacctg aggaatacct tggatggcta tggtatccac cccaagagca tagacctgga 840 caattacttc actgcccggc ggctcctcag tcaggtgagg gccctggaca ggttccaggt 900 gccaaccact gaggtaaatg cctggctggt tcaccgagac ccagaggggt ctgtctctgg 960 cagtcagccc aactcaggcc tcgccctcga gagttccagt ggcctccaag atgtgacagg 1020 cccagacaac ggggtgcgag aaagcgaaac ggagcaggga ttcggtgaag atttggagga 1080 tttgggggct gtagcccccc cagtcagtgg agacttaacc aaagaggaca tagatctgat 1140 tgacatcctt tggcgacagg atattgatct gggggctggg cgtgaggttt ttgactatag 1200 tcaccgccag aaggagcagg atgtggagaa ggagctgcga gatggaggcg agcaggacac 1260 ctgggcaggc gagggcgcgg aagctctggc acggaacctg ctagtggatg gagagactgg 1320 ggagagcttc cctgcacagg tgcctagtgg ggaggaccag acggccctgt ccctggaaga 1380 gtgccttagg ctgctggaag ccacctgccc ctttggggag aatgctgagt ttccagcaga 1440 catttccagc ataacagaag cagtgcctag tgagagtgag ccccctgctc ttcaaaacaa 1500 cctcttgtct cctcttctga ccgggacaga gtcaccattt gatttggaac agcagtggca 1560 agatctcatg tccatcatgg aaatgcaggc catggaagtg aacacatcag caagtgaaat 1620 cctgtacagt gcccctcctg gagacccact gagcaccaac tacagccttg cccccaacac 1680 tcccatcaat cagaatgtca gcctgcatca ggcgtccctg gggggctgca gccaggactt 1740 cttactcttc agccccgagg tggaaagcct gcctgtggcc agtagctcca cgctgctccc 1800 gttggccccc agcaattcta ccagcctcaa ctccaccttc ggctccacca acctgacagg 1860 gctcttcttt ccaccccagc tcaatggcac agccaatgac acagcaggcc cagagctgcc 1920 tgaccctttg gggggtctgt tagatgaagc tatgttggat gagatcagcc ttatggacct 1980 ggccattgaa gaaggcttta accctgtgca ggcctcccag ctggaggagg aatttgactc 2040 tgactcaggc ctttccttag actcgagcca tagcccttct tccctaagca gctctgaagg 2100 cagttcttcc tcttcttcct cctcctcttc ctcttcttcc tctgcttctt cctctgcctc 2160 ttcctccttt tctgaggaag gtgcggttgg ctacagctct gactctgaga ccctggatct 2220 ggaagaggcc gagggtgctg tgggctacca gcctgagtat tccaagttct gccgcatgag 2280 ctaccaggat ccagctcagc tctcatgcct gccctacctg gagcacgtgg gccacaacca 2340 cacatacaac atggcaccca gtgccctgga ctcagccgac ctgccaccac ccagtgccct 2400 caagaaaggc agcaaggaga agcaggctga cttcctggac aagcagatga gccgggatga 2460 gcaccgagcc cgagccatga agatcccttt caccaatgac aaaatcatca acctgcctgt 2520 ggaggagttc aatgaactgc tgtccaaata ccagttgagt gaagcccagc tgagcctcat 2580 ccgagacatc cggcgccggg gcaagaacaa gatggcggcg cagaactgcc gcaagcgcaa 2640 gctggacacc atcctgaatc tggagcgtga tgtggaggac ctgcagcgtg acaaagcccg 2700 gctgctgcgg gagaaagtgg agttcctgcg ctccctgcga cagatgaagc agaaggtcca 2760 gagcctgtac caggaggtgt ttgggcggct gcgagatgag aacggacgac cctactcgcc 2820 cagtcagtat gcgctccagt acgccgggga cggcagtgtc ctcctcatcc cccgcacgat 2880 ggccgaccag caggcccggc ggcaggagag gaagccaaag gaccggagaa agtgagcctg 2940 gggaagaagg gggtttgaag cccaccaaga ccgaaactgg agaagggctg gacctggacc 3000 tggacctgga cctacagcgg ggacttaaat gccttcttat ccaatatatc ttctcagatg 3060 ggatgactgc gggtcagtgt acaggaagag gcaggcactg gctggctcag ctccactcgg 3120 gtggagtgga agtggccaga ccatttagac ggacagggtc ctcaccctac ccctttcctg 3180 tgaggcaggg gtggtggtgg agttgctgga ggtagaggag ctatgtggag caaaggccga 3240 cagaggggaa ggaatggacc tgtgagagga agggaaggtg gcagaaagtc tcatttcagg 3300 aaggagggat agaaggaagg aaggaaggaa cccccccccc cccgaaaaaa aaatcaaagc 3360 gggaagaaaa tcagagggaa ggttaaggtt ggctctggcc aggattccag gcagcaggtt 3420 ggagtgactg gtgggcctag atcactggtg tgataaaccc caattttcac cccggggggg 3480 gtggggtaca cagacacagg gtgggggtgg ggagggacgg tgttaactct ttctgctcct 3540 tgcattttga catccctgaa ggggagctct tggatatcat tggccatgtt tcaatcgaat 3600 ggagccactg ggccccaaca ctggctttga gatttagagt caaagggtag agtgaacagg 3660 aaagggtcac gtggtcccat gttgcaacag ccccaacatc acgcatgtca ttcactgcct 3720 tgccactcca tctccctccg tgctccagcc acccctgagc tgaggctccc attgtctcca 3780 tcagagcctg catgtgtatg ccgtcctccc ctggtccggt gtttgtgttc cccacccctc 3840 acagactgcc tgagctcttc tgtaagctgg ggtagggtga tggcagtgct ccgggaactg 3900 ggcctgcagc cttcctcttc tgggactgct gtgaggcaga ggaatgatgg agaatctagt 3960 gtagcagcct ccaggcagga ttcagcacaa cactggggag tcacccttcc ctcgggcctc 4020 tgcctaccaa caactgggct tatcactggg aaaacacaaa aaattacaca acccagcaac 4080 aacaaaagaa ctagtcctct tagaatttct tgcgctttga tttttttagg gcttgtgccc 4140 tgtttcactt atagggtcta gaatgcttgt gttgagtaaa aaggagatgc ccaatattca 4200 aagctgctaa atgttctctt tgccataaag actccgtgta actgtgtgaa cacttgggat 4260 ttttctcctc tgtcccgagg tcgtcgtctg ctttcttttt tgggtttctt tctagaagat 4320 tgagaagtgc atatgacagg ctgagagcac ctccccaaac acacaagctc tcagccacag 4380 gcagcttctc cacagcccca gcttcgcaca ggctcctgga gggctgcctg ggggaggcag 4440 acatgggagt gccaaggtgg ccagatggtt ccaggactac aatgtcttta tttttaactg 4500 tttgccactg ctgccctcac ccctgcccgg ctctggagta ccgtctgccc cagacaagtg 4560 ggagtgaaat gggggtgggg ggaagcactg attcccagtt agggggtgcc taactgagca 4620 gtagggatag aaggtgtgaa cctgggagtg cttttataaa ttattttcct tgtagatttt 4680 atttttaatt tatctctgtg acctgccagg gagaggggag agagagagag atgctgttga 4740 gcacatgaca aaataaaata aaatggatga ttcattctta agtgcacttt ttccccactt 4800 tgaatttaaa ttgagaataa aggaaatgga ctcattgta 4839 <![CDATA[<210> 37]]> <![CDATA[<211> 690]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 37]]> ctccgccgcc ggctcccggg tgtggtggtc gcaccagctc tctgctctcc cagcgcagcg 60 ccgccgcccg gcccctccag cttcccggac catggccaac ctggagcgca ccttcatcgc 120 catcaagccg gacggcgtgc agcgcggcct ggtgggcgag atcatcaagc gcttcgagca 180 gaagggattc cgcctcgtgg ccatgaagtt cctccgggcc tctgaagaac acctgaagca 240 gcactacatt gacctgaaag accgaccatt cttccctggg ctggtgaagt acatgaactc 300 agggccggtt gtggccatgg tctgggaggg gctgaacgtg gtgaagacag gccgagtgat 360 gcttggggag accaatccag cagattcaaa gccaggcacc attcgtgggg acttctgcat 420 tcaggttggc aggaacatca ttcatggcag tgattcagta aaaagtgctg aaaaagaaat 480 cagcctatgg tttaagcctg aagaactggt tgactacaag tcttgtgctc atgactgggt 540 ctatgaataa gaggtggaca caacagcagt ctccttcagc acggcgtggt gtgtccctgg 600 acacagctct tcattccatt gacttagagg caacaggatt gatcattctt ttatagagca 660 tatttgccaa taaagctttt ggaagccgga 690 <![CDATA[<210> 38]]> <![CDATA[<211> 2630]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 38]]> agagtgaaat attactgccg agggaacgta gcagggcaca cgtctcgcct ctttgcgact 60 cggtgccccg tttctcccca tcacctactt acttcctggt tgcaacctct cttcctctgg 120 gacttttgca ccgggagctc cagattcgcc accccgcagc gctgcggagc cggcaggcag 180 aggcaccccg tacactgcag agacccgacc ctccttgcta ccttctagcc agaactactg 240 caggctgatt ccccctacac actctctctg ctcttcccat gcaaagcaga actccgttgc 300 ctcaacgtcc aacccttctg cagggctgca gtccggccac cccaagacct tgctgcaggg 360 tgcttcggat cctgatcgtg agtcgcgggg tccactcccc gcccttagcc agtgcccagg 420 gggcaacagc ggcgatcgca acctctagtt tgagtcaagg tccagtttga atgaccgctc 480 tcagctggtg aagacatgac gaccctggac tccaacaaca acacaggtgg cgtcatcacc 540 tacattggct ccagtggctc ctccccaagc cgcaccagcc ctgaatccct ctatagtgac 600 aactccaatg gcagcttcca gtccctgacc caaggctgtc ccacctactt cccaccatcc 660 cccactggct ccctcaccca agacccggct cgctcctttg ggagcattcc acccagcctg 720 agtgatgacg gctccccttc ttcctcatct tcctcgtcgt catcctcctc ctccttctat 780 aatgggagcc cccctgggag tctacaagtg gccatggagg acagcagccg agtgtccccc 840 agcaagagca ccagcaacat caccaagctg aatggcatgg tgttactgtg taaagtgtgt 900 ggggacgttg cctcgggctt ccactacggt gtgcacgcct gcgagggctg caagggcttt 960 ttccgtcgga gcatccagca gaacatccag tacaaaaggt gtctgaagaa tgagaattgc 1020 tccatcgtcc gcatcaatcg caaccgctgc cagcaatgtc gcttcaagaa gtgtctctct 1080 gtgggcatgt ctcgagacgc tgtgcgtttt gggcgcatcc ccaaacgaga gaagcagcgg 1140 atgcttgctg agatgcagag tgccatgaac ctggccaaca accagttgag cagccagtgc 1200 ccgctggaga cttcacccac ccagcacccc accccaggcc ccatgggccc ctcgccaccc 1260 cctgctccgg tcccctcacc cctggtgggc ttctcccagt ttccacaaca gctgacgcct 1320 cccagatccc caagccctga gcccacagtg gaggatgtga tatcccaggt ggcccgggcc 1380 catcgagaga tcttcaccta cgcccatgac aagctgggca gctcacctgg caacttcaat 1440 gccaaccatg catcaggtag ccctccagcc accaccccac atcgctggga aaatcagggc 1500 tgcccacctg cccccaatga caacaacacc ttggctgccc agcgtcataa cgaggcccta 1560 aatggtctgc gccaggctcc ctcctcctac cctcccacct ggcctcctgg ccctgcacac 1620 cacagctgcc accagtccaa cagcaacggg caccgtctat gccccaccca cgtgtatgca 1680 gccccagaag gcaaggcacc tgccaacagt ccccggcagg gcaactcaaa gaatgttctg 1740 ctggcatgtc ctatgaacat gtacccgcat ggacgcagtg ggcgaacggt gcaggagatc 1800 tgggaggatt tctccatgag cttcacgccc gctgtgcggg aggtggtaga gtttgccaaa 1860 cacatcccgg gcttccgtga cctttctcag catgaccaag tcaccctgct taaggctggc 1920 acctttgagg tgctgatggt gcgctttgct tcgttgttca acgtgaagga ccagacagtg 1980 atgttcctaa gccgcaccac ctacagcctg caggagcttg gtgccatggg catgggagac 2040 ctgctcagtg ccatgttcga cttcagcgag aagctcaact ccctggcgct taccgaggag 2100 gagctgggcc tcttcaccgc ggtggtgctt gtctctgcag accgctcggg catggagaat 2160 tccgcttcgg tggagcagct ccaggagacg ctgctgcggg ctcttcgggc tctggtgctg 2220 aagaaccggc ccttggagac ttcccgcttc accaagctgc tgctcaagct gccggacctg 2280 cggaccctga acaacatgca ttccgagaag ctgctgtcct tccgggtgga cgcccagtga 2340 cccgcccggc cggccttctg ccgctgcccc cttgtacaga atcgaactct gcacttctct 2400 ctcctttacg agacgaaaag gaaaagcaaa ccagaatctt atttatattg ttataaaata 2460 ttccaagatg agcctctggc cccctgagcc ttcttgtaaa tacctgcctc cctcccccat 2520 caccgaactt cccctcctcc cctatttaaa ccactctgtc tcccccacaa ccctcccctg 2580 gccctctgat ttgttctgtt cctgtctcaa atccaatagt tcacagctga 2630 <![CDATA[<210> 39]]> <![CDATA[<211> 2485]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 39]]> agtcccagtg gcggaggcta cgaaacttgg gggagtgcac agaagaactt cgggagcgca 60 cgcgggacca gggaccaggc tgagactcgg ggcgccagtc cgggcagggg cagcgggagc 120 cggccggaga tgccctgtat ccaagcccaa tatgggacac cagcaccgag tccgggaccc 180 cgtgaccacc tggcaagcga ccccctgacc cctgagttca tcaagcccac catggacctg 240 gccagccccg aggcagcccc cgctgccccc actgccctgc ccagcttcag caccttcatg 300 gacggctaca caggagagtt tgacaccttc ctctaccagc tgccaggaac agtccagcca 360 tgctcctcag cctcctcctc ggcctcctcc acatcctcgt cctcagccac ctcccctgcc 420 tctgcctcct tcaagttcga ggacttccag gtgtacggct gctaccccgg ccccctgagc 480 ggcccagtgg atgaggccct gtcctccagt ggctctgact actatggcag cccctgctcg 540 gccccgtcgc cctccacgcc cagcttccag ccgccccagc tctctccctg ggatggctcc 600 ttcggccact tctcgcccag ccagacttac gaaggcctgc gggcatggac agagcagctg 660 cccaaagcct ctgggccccc acagcctcca gccttctttt ccttcagtcc tcccaccggc 720 cccagcccca gcctggccca gagccccctg aagttgttcc cctcacaggc cacccaccag 780 ctgggggagg gagagagcta ttccatgcct acggccttcc caggtttggc acccacttct 840 ccacaccttg agggctcggg gatactggat acacccgtga cctcaaccaa ggcccggagc 900 ggggccccag gtggaagtga aggccgctgt gctgtgtgtg gggacaacgc ttcatgccag 960 cattatggtg tccgcacatg tgagggctgc aagggcttct tcaagcgcac agtgcagaaa 1020 aacgccaagt acatctgcct ggctaacaag gactgccctg tggacaagag gcggcgaaac 1080 cgctgccagt tctgccgctt ccagaagtgc ctggcggtgg gcatggtgaa ggaagttgtc 1140 cgaacagaca gcctgaaggg gcggcggggc cggctacctt caaaacccaa gcagccccca 1200 gatgcctccc ctgccaatct cctcacttcc ctggtccgtg cacacctgga ctcagggccc 1260 agcactgcca aactggacta ctccaagttc caggagctgg tgctgcccca ctttgggaag 1320 gaagatgctg gggatgtaca gcagttctac gacctgctct ccggttctct ggaggtcatc 1380 cgcaagtggg cggagaagat ccctggcttt gctgagctgt caccggctga ccaggacctg 1440 ttgctggagt cggccttcct ggagctcttc atcctccgcc tggcgtacag gtctaagcca 1500 ggcgagggca agctcatctt ctgctcaggc ctggtgctac accggctgca gtgtgcccgt 1560 ggcttcgggg actggattga cagtatcctg gccttctcaa ggtccctgca cagcttgctt 1620 gtcgatgtcc ctgccttcgc ctgcctctct gcccttgtcc tcatcaccga ccggcatggg 1680 ctgcaggagc cgcggcgggt ggaggagctg cagaaccgca tcgccagctg cctgaaggag 1740 cacgtggcag ctgtggcggg cgagccccag ccagccagct gcctgtcacg tctgttgggc 1800 aaactgcccg agctgcggac cctgtgcacc cagggcctgc agcgcatctt ctacctcaag 1860 ctggaggact tggtgccccc tccacccatc attgacaaga tcttcatgga cacgctgccc 1920 ttctgacccc tgcctgggaa cacgtgtgca catgcgcact ctcatatgcc accccatgtg 1980 cctttagtcc acggaccccc agagcacccc caagcctggg cttgagctgc agaatgactc 2040 caccttctca cctgctccag gaggtttgca gggagctcaa gcccttgggg agggggatgc 2100 cttcatgggg gtgaccccac gatttgtctt atccccccca gcctggcccc ggcctttatg 2160 ttttttgtaa gataaaccgt ttttaacaca tagcgccgtg ctgtaaataa gcccagtgct 2220 gctgtaaata caggaagaaa gagcttgagg tgggagcggg gctgggagga agggatgggc 2280 cccgccttcc tgggcagcct ttccagcctc ctgctggctc tctcttccta ccctccttcc 2340 acatgtacat aaactgtcac tctaggaaga agacaaatga cagattctga catttatatt 2400 tgtgtatttt cctggattta tagtatgtga cttttctgat taatatattt aatatattga 2460 ataaaaaata gacatgtagt tggaa 2485 <![CDATA[<210> 40]]> <![CDATA[<211> 2386]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 40]]> agcccgcgcg ctcgcagctt ctcgctctcg cctgcctgcc cgctcccttg cttgctcgcg 60 ctttcgctcg ccctctcctc gaggatcgag gggactctga ccacagcctg tggctgggaa 120 gggagacaga ggcggcggcg gctcagggga aacgaggctg cagtggtggt agtaggaaga 180 tgtcgggcga ggacgagcaa caggagcaaa ctatcgctga ggacctggtc gtgaccaagt 240 ataagatggg gggcgacatc gccaacaggg tacttcggtc cttggtggaa gcatctagct 300 caggtgtgtc ggtactgagc ctgtgtgaga aaggtgatgc catgattatg gaagaaacag 360 ggaaaatctt caagaaagaa aaggaaatga agaaaggtat tgcttttccc accagcattt 420 cggtaaataa ctgtgtatgt cacttctccc ctttgaagag cgaccaggat tatattctca 480 aggaaggtga cttggtaaaa attgaccttg gggtccatgt ggatggcttc atcgctaatg 540 tagctcacac ttttgtggtt gatgtagctc aggggaccca agtaacaggg aggaaagcag 600 atgttattaa ggcagctcac ctttgtgctg aagctgccct acgcctggtc aaacctggaa 660 atcagaacac acaagtgaca gaagcctgga acaaagttgc ccactcattt aactgcacgc 720 caatagaagg tatgctgtca caccagttga agcagcatgt catcgatgga gaaaaaacca 780 ttatccagaa tcccacagac cagcagaaga aggaccatga aaaagctgaa tttgaggtac 840 atgaagtata tgctgtggat gttctcgtca gctcaggaga gggcaaggcc aaggatgcag 900 gacagagaac cactatttac aaacgagacc cctctaaaca gtatggactg aaaatgaaaa 960 cttcacgtgc cttcttcagt gaggtggaaa ggcgttttga tgccatgccg tttactttaa 1020 gagcatttga agatgagaag aaggctcgga tgggtgtggt ggagtgcgcc aaacatgaac 1080 tgctgcaacc atttaatgtt ctctatgaga aggagggtga atttgttgcc cagtttaaat 1140 ttacagttct gctcatgccc aatggcccca tgcggataac cagtggtccc ttcgagcctg 1200 acctctacaa gtctgagatg gaggtccagg atgcagagct aaaggccctc ctccagagtt 1260 ctgcaagtcg aaaaacccag aaaaagaaaa aaaagaaggc ctccaagact gcagagaatg 1320 ccaccagtgg ggaaacatta gaagaaaatg aagctgggga ctgaggtggg tcccatctcc 1380 ccagcttgct gctcctgcct catccccttc ccaccaaacc ccagactctg tgaagtgcag 1440 ttcttctcca cctaggaccg ccagcagagc ggggggatct ccctgccccc accccagttc 1500 cccaacccac tcccttccaa caacaaccag ctccaactga ctctggtctt gggaggtgag 1560 gcttcccaac cacggaagac tactttaaat gaaaaaaaga aattgaataa taaaatcagg 1620 agtcaaaatt catcgtcttc aagcccctct ttctagcctt ttctactact ctctgcttgg 1680 tcaaggtttg tgccccacta cagaacaggg ctaaattagc caccaccact gaaaactcag 1740 ccgaattttt ttataccact ctgatgtcag cattttttcc atctgtttgg ggctttttcc 1800 tcttttttcc attctcccca aatattttat ctggcttcaa aattaagagg attatttttc 1860 agattgtttt tattcagtgt ggccgattcc tcatctgatt caggctgtcc agtcaggccc 1920 ctcccatttt aggagctgga gccttcattt atgaagagat tctcatctat gaaatggatc 1980 ctcatttgta aatctttttt cttccatttt cacaaagctg taaagaaata atccatctca 2040 accttaccct ttttctctgg agtcagtggg gtctttcctc gctccatctt acacagacct 2100 gagctggaag ctcaactggt tttgttccct gtttgaaata ttgtgatctc cctcccatga 2160 aagaaaaacc aagaaccaga ggcgtagact gactgaagac acaactcctg gctttctgaa 2220 gctatggact tggattggat tgctgggggt ttgtagagaa aggtgacaaa tttcagtacc 2280 tctggcatgc tgtcccagga aactagggct cccactaact tatgaggttt ttaaacacat 2340 tgaaaatgac atgacattaa aataaatttg gatttgctca taatga 2386 <![CDATA[<210> 41]]> <![CDATA[<211> 4460]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 41]]> attcgacagt ccccgctctg agagggaggg acagagagcg aactgtcaga tcggagcgag 60 agcgggcgcc cgagagaggg agagagagag agggagggag aggaaaagtg agagagggaa 120 agagagcgcg aacgagggcg cagagcgagc tcctgctgca actctgctcc agcacggcca 180 gcgccagcgc ccgccgtcgg tgcactctac gagccgtgca gcgtgcccac tggagttgtt 240 gtgtatcaag gatcgatccc ctatatgcac acacacacct ccacctccac caatgcactc 300 ttcttcctcc tccttctcca gacaactgct gggaaaaaaa taaaacacca accccaaccg 360 tcagcaacaa ggtaacagag cgattcgaca tcattttttt tcctgttcaa ttttttcctt 420 gttatatttg tttcctaatt tctgcccaaa aggaaagatg tcgcatcaga ctgtgactgt 480 tgcgaggaga atgaaaaagg actcttgttt cagaggcaac caagagctcc ggcaatagca 540 acttcagaga aatgcaccat cgcaagaagt tttcctagga cagaacaaaa cttgaaacga 600 gaggaccaga gggggagagc aggagccagc ctcccctctc cgcactcgcg agcagccagc 660 agcaccacgc cttcaaggac gaaaaagttt tactactcta agggaaaacg agtgaaatgt 720 gttcctgagg aggagaggag aggagaggag agagcggaca agagaaggag cgggccggtt 780 gctggtcatc cgtaatttgg ctaaggaaga aaggagcagc ttctttcttt gttatctccc 840 gtgaaacctt cacttagcag gtggacggag ccccgcgacc gggcagagtc cgggctcgcc 900 cgaggacagg aggaggagcg ggagcccgcg cgtcccggga gagcgccccg agtgcaggtc 960 cccgccccgc ccggcgagcc ccgctggagc gagcccagcg cgccggggct ggggggcggc 1020 cacgaccccc cctgaagggg gtggccacgg agcgcacccc gagaagcgag cccccctccc 1080 cagagcgctg ctcctgcggc tgctgctgct gctggtgacc aaggccggcc ggcgaccccc 1140 gcgccctgcc gagcggcctt gcagctgcag ccgggggccg cggcggcggc ggcggcggcg 1200 ggggcggagg cggcggcgga ggaggaggcg gcgaaggcgg cggggccggc gggggcccgg 1260 ggcgggggcg gggaaggagg gggggaggag gcgggaggcg gggggcgcgg cggcggcggc 1320 ggcggcggcg gccgcggctg ctgctgcggc ggcggcggcg gtggtggcgg cggtggggtg 1380 gcgggagcgg agcggcatgg ccacggcggc ttctaacccc tacctgccgg ggaacagcct 1440 gctcgcggcc ggctctattg tgcactcgga cgcggcaggg gctggcggcg gcgggggtgg 1500 cggcggcggc ggcggcgggg gcggcgcagg gggcgggggc ggcggcatgc agccgggcag 1560 cgccgccgtg acctcgggcg cctaccgggg ggacccgtcc tctgtcaaga tggtccagag 1620 cgacttcatg cagggggcca tggccgccag caacggcggc catatgctga gccacgcgca 1680 ccagtgggtc acagccctgc cccacgccgc cgccgccgcc gccgctgccg ccgccgccgc 1740 cgtggaggcg agctcgccgt ggtcgggcag cgccgtgggc atggctggca gcccccagca 1800 gccaccgcag ccgccgccgc caccgccgca gggccccgac gtgaagggcg gcgccgggcg 1860 cgacgacctg cacgcgggca cagcgctgca ccaccgcggg ccgccgcacc tcggaccccc 1920 gccgccgccc ccacaccagg gccaccctgg gggctggggg gcggccgccg ctgccgcagc 1980 cgcagccgcc gccgccgccg ccgccgcgca cctcccgtcc atggccgggg gccagcagcc 2040 gccgccgcag agtctgctct actcgcagcc cggaggcttc acggtgaacg gcatgctgag 2100 cgcgccaccg gggcccggcg gcggcggcgg cggcgcgggc ggtggagccc agagcttggt 2160 gcacccgggg ctggtgcgcg gggacacgcc agagctggcc gagcaccacc accaccacca 2220 ccaccacgcg catcctcacc cgccgcaccc gcaccacgcg cagggacccc cgcaccacgg 2280 cggcggcggc ggcggcgcgg ggcctggact caacagccac gacccgcact cggacgagga 2340 cacgccgacg tcggacgacc tggagcagtt cgccaagcag ttcaagcagc ggcgcatcaa 2400 gctgggcttc acgcaggccg acgtggggtt ggcgctgggc acactctacg gcaacgtgtt 2460 ctcgcagacc accatctgcc gcttcgaggc cctgcagctg agcttcaaga acatgtgcaa 2520 gctcaagccg ctgctgaaca agtggctgga ggaggcggac tcaagcaccg gcagccccac 2580 aagcatcgac aagatcgcgg cgcagggccg caagcgcaag aagcggacct ctatcgaggt 2640 gagcgtcaag ggcgcgctgg agagccactt cctcaagtgc cccaagccct ccgcgcagga 2700 gatcaccaac ctggccgaca gcctgcagct cgagaaggag gtggtgcggg tctggttctg 2760 caatcggcgc caaaaggaga agcgcatgac gccgcccggg atccaacagc agacgcccga 2820 cgacgtctac tcgcaggtgg gcaccgtgag cgccgacacg ccgccgcctc accacgggct 2880 gcagacgagc gttcagtgaa gccagggcgc agagcgaaga gggccgccgc cgccgccgcc 2940 tccgcagccg ccgtcagcac cgccgccgcc cctgccgccg ccgccgccgc cgccgccgcc 3000 gctgccgccg ccgcgccgac cctgcacctg ggccgctccg ggctccagcc caggcccatc 3060 cgccgccctc ccctccaccc agagacaggc atgcccgccc ttggaggaga aaacgcggga 3120 gaaacggacc aaggaggcat ttttgcagtc caaggaagga ggggccaaaa aataaaaagc 3180 ataataaaca cccagactgt tttgtataca tatataacaa acaaaaccgg aagagaaaaa 3240 gggggcgatc atgagatctc gttcatactg tggtggtgtt tcgtttttgt ttttgttttt 3300 aaagaagggt gaagatgcct gacgcacgaa aactgcactc gtgaggtttt tccaccctga 3360 gatgacctac acggcagcgg tggacagcac ctgcctcgtc ttctcctctt tgaaaaaaag 3420 agagagagag agtccccttt cctttcactt tctccctcca aaacagctgc ctaaagagat 3480 ccacggaaac tttatttcct gggagcgacc tgagagaaaa cagaggcacc aggttccatc 3540 aggggacgac accgtgctct gggaccctgt ttttcttggc catattaaag tcatttggaa 3600 acaaatcaac tctgaaatgg gaaggagggg ggaaaaacag tctccaagaa aaaaataatt 3660 atattgacag cttctgaaac taacagactg aatagcaaag ccaaaagaaa agtatcctca 3720 aagtaacctt ggaaataaaa ggatcgggaa ggagcagagg gagaggggga acgtccgctg 3780 aggagtggcg agaggccccg gccgagtcgg gtcgcgggcg ggcgggcgaa ctgggagcag 3840 agcgggggcc cagccagcga ggccgccgag ccaggcccgg ccgcgtaccc aggctttgac 3900 ggctgccatt cagggtggac gatgcctaaa gattccaccg ctaatatttt ttttattaat 3960 attttttatt ttttatttct ggactgactc agataaagga atttagaaag actgagcacc 4020 agccgctgca cttctctgga cttctctcct caatccgttg ccaactttga ttgaatgggt 4080 gctgtggatg tgattatata atactgccat ttccaagcag tgtttttggt aggttttaat 4140 aaacagactt ttcaaaagac ggcaatatag aattgttaga tccgttgttg atctaaaaat 4200 atttgcttta tattttcatt aaatgacttc ttttaatatt ttattcagaa tacttatgaa 4260 ctgctgcaaa acggtaattt atttttcccc agatcttgta ttacgtgttt ttttcagacg 4320 agcacaaatc aaaatgaaat gaaaatatgg acagttgtta ggtaataagg gtatcttttg 4380 atgtgatcat ttgattgtaa tttaatttga gtagtgattc cgtaagagct gatcgagaaa 4440 ataaatttgt tagaatgaaa 4460 <![CDATA[<210> 42]]> <![CDATA[<211> 2517]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 42]]> atttccgcct ctggcgaatg gctcgtctgt agtgcacgcc gcgggcccag ctgcgacccc 60 ggccccgccc ccgggacccc ggccatggac gaactgttcc ccctcatctt cccggcagag 120 ccagcccagg cctctggccc ctatgtggag atcattgagc agcccaagca gcggggcatg 180 cgcttccgct acaagtgcga ggggcgctcc gcgggcagca tcccaggcga gaggagcaca 240 gataccacca agacccaccc caccatcaag atcaatggct acacaggacc agggacagtg 300 cgcatctccc tggtcaccaa ggaccctcct caccggcctc acccccacga gcttgtagga 360 aaggactgcc gggatggctt ctatgaggct gagctctgcc cggaccgctg catccacagt 420 ttccagaacc tgggaatcca gtgtgtgaag aagcgggacc tggagcaggc tatcagtcag 480 cgcatccaga ccaacaacaa ccccttccaa gttcctatag aagagcagcg tggggactac 540 gacctgaatg ctgtgcggct ctgcttccag gtgacagtgc gggacccatc aggcaggccc 600 ctccgcctgc cgcctgtcct ttctcatccc atctttgaca atcgtgcccc caacactgcc 660 gagctcaaga tctgccgagt gaaccgaaac tctggcagct gcctcggtgg ggatgagatc 720 ttcctactgt gtgacaaggt gcagaaagag gacattgagg tgtatttcac gggaccaggc 780 tgggaggccc gaggctcctt ttcgcaagct gatgtgcacc gacaagtggc cattgtgttc 840 cggacccctc cctacgcaga ccccagcctg caggctcctg tgcgtgtctc catgcagctg 900 cggcggcctt ccgaccggga gctcagtgag cccatggaat tccagtacct gccagataca 960 gacgatcgtc accggattga ggagaaacgt aaaaggacat atgagacctt caagagcatc 1020 atgaagaaga gtcctttcag cggacccacc gacccccggc ctccacctcg acgcattgct 1080 gtgccttccc gcagctcagc ttctgtcccc aagccagcac cccagcccta tccctttacg 1140 tcatccctga gcaccatcaa ctatgatgag tttcccacca tggtgtttcc ttctgggcag 1200 atcagccagg cctcggcctt ggccccggcc cctccccaag tcctgcccca ggctccagcc 1260 cctgcccctg ctccagccat ggtatcagct ctggcccagg ccccagcccc tgtcccagtc 1320 ctagccccag gccctcctca ggctgtggcc ccacctgccc ccaagcccac ccaggctggg 1380 gaaggaacgc tgtcagaggc cctgctgcag ctgcagtttg atgatgaaga cctgggggcc 1440 ttgcttggca acagcacaga cccagctgtg ttcacagacc tggcatccgt cgacaactcc 1500 gagtttcagc agctgctgaa ccagggcata cctgtggccc cccacacaac tgagcccatg 1560 ctgatggagt accctgaggc tataactcgc ctagtgacag gggcccagag gccccccgac 1620 ccagctcctg ctccactggg ggccccgggg ctccccaatg gcctcctttc aggagatgaa 1680 gacttctcct ccattgcgga catggacttc tcagccctgc tgagtcagat cagctcctaa 1740 gggggtgacg cctgccctcc ccagagcact gggttgcagg ggattgaagc cctccaaaag 1800 cacttacgga ttctggtggg gtgtgttcca actgccccca actttgtgga tgtcttcctt 1860 ggagggggga gccatatttt attcttttat tgtcagtatc tgtatctctc tctctttttg 1920 gaggtgctta agcagaagca ttaacttctc tggaaagggg ggagctgggg aaactcaaac 1980 ttttcccctg tcctgatggt cagctccctt ctctgtaggg aactctgggg tcccccatcc 2040 ccatcctcca gcttctggta ctctcctaga gacagaagca ggctggaggt aaggcctttg 2100 agcccacaaa gccttatcaa gtgtcttcca tcatggattc attacagctt aatcaaaata 2160 acgccccaga taccagcccc tgtatggcac tggcattgtc cctgtgccta acaccagcgt 2220 ttgaggggct ggccttcctg ccctacagag gtctctgccg gctctttcct tgctcaacca 2280 tggctgaagg aaaccagtgc aacagcactg gctctctcca ggatccagaa ggggtttggt 2340 ctgggacttc cttgctctcc ctcttctcaa gtgccttaat agtagggtaa gttgttaaga 2400 gtgggggaga gcaggctggc agctctccag tcaggaggca tagtttttac tgaacaatca 2460 aagcacttgg actcttgctc tttctactct gaactaataa atctgttgcc aagctgg 2517 <![CDATA[<210> 43]]> <![CDATA[<211> 3433]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 43]]> gttagcgcag gggatccgag ctgggcagga catgtgagat agtcacagtt ttccagagat 60 cacgacaaga tctaaccagt cgcgcgtggt ccccggcgcc ggagcgggcc agctcagccc 120 ggcccagccc ggccccgcgc agagcccccg ccgcccccgc gcacagagcc gggtgcccct 180 tgcggtgcgc cggacgggaa gccccgagga gcagctgctg cgcccgccac ccgggtcgtc 240 cgtccaccgc gcgcgccgcc gcccgggccg ggggtccgag ccgcgcgccc ccggccccgg 300 ccccggcccc cgggcgcctg ggccggatgt cccgatgaga gagccggcgc tggcggccag 360 cgccatggct taccacccgt tccacgcgcc acggcccgcc gacttcccca tgtccgcctt 420 tctggcggcg gcgcagccct ccttcttccc ggcactcgcg ctgccgcccg gcgcgctggc 480 caagccgctg cccgacccgg gcctggcggg ggcggcggcc gcggcggcgg cggcggcagc 540 agcggccgag gcggggctgc acgtctcggc actgggcccg cacccgcccg ccgcgcatct 600 gcgctccctc aagagcctgg agcccgagga cgaggtggag gacgacccca aggtgacgct 660 ggaggccaag gagctgtggg accagttcca caagctaggc acggagatgg tcatcaccaa 720 gtccgggagg cggatgttcc cccccttcaa ggtgcgagtc agcggcctgg acaagaaggc 780 caagtatatc ctgctgatgg acattgtagc cgctgacgat tgccgctata agttccacaa 840 ctcgcgctgg atggtggcgg gcaaggccga ccctgagatg cccaaacgca tgtacatcca 900 cccagacagc ccagccacgg gggagcagtg gatggctaag cctgtggcct tccacaagct 960 gaagctgacc aacaacatct ctgacaagca cggcttcacc atcctaaact ccatgcacaa 1020 gtaccagccg cgcttccaca tagtgcgagc caacgacatc ctgaagctgc cttacagcac 1080 cttccgcacc tacgtgttcc cggagaccga cttcatcgcc gtcactgcct accagaatga 1140 caagatcaca cagctgaaga tcgacaacaa cccgtttgcc aagggcttcc gggacaccgg 1200 gaacggccgg cgggagaaaa ggaagcagct gacgctgccg tctctacgct tgtacgagga 1260 gcactgcaaa cccgagcgcg atggcgcgga gtcagacgcc tcgtcgtgcg accctccccc 1320 cgcgcgggaa ccacccacct ccccgggcgc agcgcccagt ccgctgcgcc tgcaccgggc 1380 ccgagctgag gagaagtcgt gcgccgcgga cagcgacccg gagcctgagc ggttgagcga 1440 ggagcgtgcg ggggcgccgc taggccgcag cccggctcca gacagcgcca gccccactcg 1500 cttgaccgaa cccgagcgcg cccgggagcg gcgtagtccc gagaggggca aggagccggc 1560 cgagagcggc ggggacggcc cgttcggcct gaggagcctg gagaaggagc gcgccgaagc 1620 tcggaggaag gacgaggggc gcaaggaggc ggccgagggc aaggagcagg gcctggcgcc 1680 gctggtggtg cagacagaca gtgcgtcccc cctgggcgcc ggacacctgc ccggcctggc 1740 cttttccagc cacttgcacg ggcagcagtt ctttgggccg ctgggagccg gccagccgct 1800 cttcctgcac cctggacagt tcaccatggg ccctggcgcc ttctccgcca tgggcatggg 1860 tcacctactg gcctcggtgg caggcggcgg caacggcgga ggtggcgggc ctgggaccgc 1920 cgcggggctg gacgcaggcg ggctgggtcc cgcggccagc gcagcaagca ccgccgcgcc 1980 cttcccgttc cacctctccc agcacatgct ggcatctcag ggaattccaa tgcccacttt 2040 cggaggcctc ttcccctacc cctacaccta catggcagca gcagccgcag ccgcctcggc 2100 tttgcccgcc actagtgctg cagctgccgc cgccgcagcc gccggctccc tctcccggag 2160 ccccttcctg ggcagtgccc ggccccgact gcgtttcagc ccctatcaga tcccggtcac 2220 catcccgcct agcactagcc tcctcaccac cgggctggcc tctgagggct ccaaggccgc 2280 tggtggaaac agccgggagc ctagccccct gcccgagctg gctctccgca aagtaggggc 2340 cccatcccgc ggtgccctgt cgcccagtgg ctcggccaag gaggcggcca atgaactgca 2400 gagcatccag agactggtga gtgggctgga gagccagcga gccctctccc caggccggga 2460 gtcgcccaag tgaggggctg cccagctgct cccctgccac gcaggccacc cgggctgcct 2520 gcccctgctg cttgggacgt gtacagcaca gaatgagtat ttatttaaat aaaggagaaa 2580 agtgggctgc agcagccgga atagagcctc gtctggcaag tcggggcctg ggacacttcc 2640 ctgggcctca acaaggatca ggctgctgga aacacagtca cttgggagct gctgggctag 2700 gtccagatcc gctccagcgt caaggtggca tccgaaggtg tctctggtct tccagcgagg 2760 tgggagaggc ctcatccagg gcccagcggt ccctgcagaa gccagaaggt gcaggggcca 2820 ggggtgggag catcggaggg agtcccagag ccctggacct tgggcctaga ccgcgtgata 2880 aaactgggtt gagggatgct ggaaccagtt acgactgaag tcagtgtaga cctgagctgg 2940 gagggaacct gttagtctcc ccacctcttc cctgaagaga caggcacccc tcccagccgt 3000 ggtcaacgga gggagtggca cttctgcctt gagtccccag gggaaaaaaa aaaaagatat 3060 ttatgaaata aatggtaatt tgtgtaaata agctttaagg ttcccagaat atgcaaattg 3120 gtattaattt attcaaaggt gtacattgct gtgtacatat atttagagat taactcatac 3180 atttaaagtt tttttcattt tacgtgagca tctatattgt acagggctgg gggggccctt 3240 ggctgcggga gaaggcccag agccctggag gagccaccac cccgccggcc cctcgacccc 3300 tcggcccctc ggcccctccg cccgggtttg gctcgcccgg cccgcgggct ccacctcagg 3360 ttttcacttt tcgctccgga gcgagaacga aacgacaaaa acgcaagaaa acaataaaac 3420 gctagaaagc gaa 3433 <![CDATA[<210> 44]]> <![CDATA[<211> 2639]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 44]]> actcggccca gggcagggac cccgccacgg ccgggaccgc ccggcccggc cccagcccgc 60 gcctctccgc gccgccccgc gctccgcacc gcgccctctc cgcgtccccg cccgcgcggc 120 cggaccgggc agccagaaaa atcatttttc ttctctggga aggtgaacat ttgtagcatt 180 gatttcccgg atctggtaac atggcaaaag atgccggtct aattgaagcc aacggagaac 240 tcaaggtctt catagaccag aaccttagtc ccgggaaagg cgtggtgtcc ctcgtggccg 300 ttcacccctc caccgtcaac ccgctcggga agcagctctt gccaaaaacc tttggacagt 360 ccaatgtcaa cattgcccag caagtggtaa ttggtacgcc tcagagaccg gcagcgtcaa 420 acaccctggt ggtaggaagc ccacacaccc ccagcactca ctttgcctct cagaaccagc 480 cttccgactc ctcaccttgg tctgccggga agcgcaacag gaaaggagag aagaatggca 540 agggcctacg gcatttctcc atgaaggtct gcgagaaggt gcagaggaaa gggaccactt 600 cctacaacga agtggcagac gagctggttg cggagttcag tgctgccgac aaccacatct 660 taccaaacga gtcagcttat gaccagaaaa acataagacg gcgcgtctac gatgccttaa 720 acgtgctaat ggccatgaac atcatctcca aggagaagaa ggagatcaag tggattggtc 780 tgcccaccaa ctcggctcag gaatgtcaga acttagaggt ggaaagacag aggagacttg 840 aaagaataaa acagaaacag tctcaacttc aagaacttat tctacagcaa attgccttca 900 agaacctggt gcagagaaac cggcatgcgg agcagcaggc cagccggcca ccgccaccca 960 actcagtcat ccacctgccc ttcatcatcg tcaacaccag caagaagacg gtcatcgact 1020 gcagcatctc caatgacaaa tttgagtatc tgtttaattt tgacaacaca tttgaaatcc 1080 acgatgacat agaagtgctg aagcggatgg gcatggcttg cgggctggag tcggggagct 1140 gctctgccga agaccttaaa atggccagaa gtctggtccc caaggctctg gagccatacg 1200 tgacagaaat ggctcaggga actgttggag gcgtgttcat cacgacggca ggttccacgt 1260 ctaacggcac aaggttctct gccagtgacc tgaccaacgg tgcagatggg atgctggcca 1320 caagctccaa tgggtctcag tacagcggct ccagggtgga gactccggtg tcctacgtcg 1380 gggaggacga cgaggaggac gatgacttca acgagaatga cgaggacgac tgacgtcctc 1440 cccacttcag attcggcttc aggaaaacgt ttagcgaaaa gaaacttttt ttttaatgtg 1500 ggttttctgt ttccttttgg cctactccca agaagatatt ggtaagctat tgaatttaga 1560 tatgcacctc tgataagcaa ggattgtttc ccgtaggatt aggacgtgct gtggatgtgt 1620 gttttgatac cagtgtgctg atgcagagcg tttatttact tgttaggatt ttgtgttttc 1680 atttgctatt tttctttaag tgcagagttc atttttgccc ctgaaaagtt tttgctgagt 1740 ttgctgaaga aattgtattt caaccacatc catgaaaata aaacacctcc tgttgtggat 1800 ggtgagcccc tgatgccgct tatttgccgt gagtttggac ggcacccctg ctggcggata 1860 gcaagactct gtggagtttg ttcagtggta cggtgtccaa gcaaacagca gaatgcaact 1920 ttctaaacag ccccaagcaa acagcagaat tcaacttttt aaacaataaa caccatcaac 1980 cttattgact ttattgtccc ttaaattata ttgactgttg tgattccatc aagtttgtac 2040 actcttttct ctccctgttt tgcagcaaca aattgcgaag tgcttttgtt tgtttgtttt 2100 cgtttggtta aagcttattg ccatgctggt gcggctatgg agactgtctg gaaggcttgg 2160 aatggtttat tgcttatggt aaaatttgcc tgatttctta caggcagcgt ttggaaacct 2220 tttattatat agttgtttac atacttataa gtctatcatt taaagacatg tactgaaaca 2280 aatgtatttg tttcataagc atcttcctgt aatctattat aaaattgaaa ttaaatatag 2340 agaatgtttt aacaattttt taactcaaaa tttgtcaatc atttttaata gttctttttt 2400 tataaaaaga aaaaggaatt taaggacagg cagtagtctc ttttaaaatt tattcacaaa 2460 acccattaac tgcacagttg ctattagctg cctgttctaa aacgatagtc tttttattga 2520 aacacaaata aacttttctg taatatttta tggtatataa agagacttta attgtttgac 2580 ttgtttaact tggcactgtt agtttttatt aataaaacgc gcatgggcat tttaaacaa 2639 <![CDATA[<210> 45]]> <![CDATA[<211> 3148]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 45]]> gtctagagct gagtggagcc cggctgcgga tctgggaagc gcctcttcac ggcactggga 60 tccgcatctg cctgggatca tcaagcccta gaagctgggt ttctttaaat tagggctgcc 120 gttttctgtt tctccctggg ctgcggaaag ccagaagatt ttatctagct tatacaaggc 180 tgctggtgtt ccctcttttt ttccacgagg gtgtttttgg ctgcaattgc atgaaatccc 240 aatggtgtag accagtggcg atggatctag gagtttacca actgagacat ttttcaattt 300 ctttcttgtc atccttgctg gggactgaaa acgcttctgt gagacttgat aatagctcct 360 ctggtgcaag tgtggtagct attgacaaca aaatcgagca agctatggat ctagtgaaaa 420 gccatttgat gtatgcggtc agagaagaag tggaggtcct caaagagcaa atcaaagaac 480 taatagagaa aaattcccag ctggagcagg agaacaatct gctgaagaca ctggccagtc 540 ctgagcagct tgcccagttt caggcccagc tgcagactgg ctccccccct gccaccaccc 600 agccacaggg caccacacag ccccccgccc agccagcatc gcagggctca ggaccaaccg 660 catagctgcc tatgcccccg cagaactggc tgctgcgtgt gaactgaaca gacggagaag 720 atgtgctagg gagaatctgc ctccacagtc acccatttca ttgctcgctg cgaaagagac 780 gtgagactga catatgccat tatctctttt ccagtattaa acactcatat gcttatggct 840 tggagaaatt tcttagttgg gtgaattaaa ggttaatccg agaattagca tggatatacc 900 gggacctcat gcagcttggc agatatctga gaaatggttt aattcatgct caggagctgt 960 gtgcctttcc atcccttccg gctccctacc cctcacttcc aagggttctc tctcctgctt 1020 gcgcttagtg tcctacatgg ggttgtgaag cgatggagct cctcactgga ctcgcctctc 1080 tcctctcctc cccccaggag gaacttgaaa ggagggtaaa aagactaaaa tgagggggaa 1140 cagagttcac tgtacaaatt tgacaactgt caccaaaatt cataaaaaac aatagtactg 1200 tgcctctttc ttctcaaaca atggatgaca caaaactatg agagtgacaa aatggtgaca 1260 ggtagctggg acctaggcta tcttaccatg aaggttgttt tgcttattgt atatttgtgt 1320 atgtagtgta actattttgt acaatagagg actgtaacta ctatttaggt tgtacagatt 1380 gaaatttagt tgtttcattg gctgtctgag gaggtgtgga cttttatata tagatctaca 1440 taaaaactgc tacatgacaa aaaccacacc taaagaaatt ttaagaattt ggcacagtta 1500 ctcactttgt gtaatctgaa atctagctgc tgaatacgct gaagtaaatc cttgttcact 1560 gaagtctttc aattgagctg gttgaatact ttgaaaaatg ctcagttcta actaatgaaa 1620 tggatttccc agtaggggtt tctgcatatc acctgtatag tagttatatg catatgtttc 1680 tgtgcatgtt ctctacacaa ttgtaaggtg tcactgtatt taactgttgc acttgtcaac 1740 tttcaataaa gcatataaat gttgataaac aagtgttttt catatgaccc tgttaacata 1800 atggcagtca tttccacaac tgtttccagg taaagttaac aatttgacta gtaaaatcct 1860 gaagggcagt ggaatgattg gaaaagtagg ggcgtgattt gactgcatga agtaaaagga 1920 aattgacaca ttgagttgtt cagcaggtaa gagaagagac agtggaggag tccagctcaa 1980 ttctaactac tgtgtgactt ggacaggttg cttcactcct ggacggatgt aggggtttga 2040 aagagatgat ctcttacatt cccctttggc tttaaaattc taggagtcct tgaaaatctt 2100 aattttttac tgaactgaga ggaagaagga gccttattct gtgtataatt ggaataagca 2160 gatctaggat caaaagacgg aagttggaga agctgatttc cactttaaga accctgtcac 2220 cctgggttgg gatgtttctc ctagtgtagg atgagtttct agctcctggg ataattcgtt 2280 ttgtctaagc aaaagatgat ttgaggtggg accagatgag caaggatgtc cttgcagttg 2340 attctgcatg actataaaac aggccaaaat taaaaccacg aaggaatcct gaggcagatt 2400 ggcccctggc acctgaggag tgagcctgag ggatcccact ctgcagtagg agtaacgtga 2460 gcgagcaagt gaatggggtg ggtttaccgg ctctgtaatc tatcaaccta gggcctcagc 2520 agtggccccc tgcccagtag gaattggacc aatcccaagt tctaaggctt gtcttaagtc 2580 cttgcagaac aaggacaaac tttctgaatc attcatttct ctcatctaga gctggtggga 2640 gattgagagg tgaatgggac atccaagatc cctaaaaaga attgttcgat agcgtgcatg 2700 tgttataaag tggtgacacg ggcatcctgt tgaaatgatg gatggctcac tgccataggc 2760 tgatagcagt tgtcataaag atattttggg ggaatttgaa aaggacgtaa agaaaaatct 2820 ttcatattgg cttgttggtt atataacttc aaatttaata aaggaatact tacgtagtaa 2880 ttacatttcc ttgaaaaaac tatagtgaat agaaatccct agccatttca ttttttatgt 2940 ttttaatgaa gatctttaaa ataccatagg tggtaatcgt ggaaaatttg aaaaatctca 3000 tgtcagtgta ttaagatggt ggagaagttt ttttctccat tatttaatgg aactttgggt 3060 ctttttatta aaaatgtgag actcatgaaa ttttggcagc tgaatatttg tgaaataaga 3120 atgaattatt aaaagatgtc tttccata 3148 <![CDATA[<210> 46]]> <![CDATA[<211> 1746]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 46]]> gtatctcctc cgtcccctcc tgccgcgcgg cgtgagcgcc gggctcgggg cccccccggc 60 cgcccgcccc ctcccctccc tccctcccct cccctcccct cccccccggg ccccgcgccc 120 cccccgcccc cgcccccccc atggacatgc tggacccggg tctggatccc gctgcctcgg 180 ccaccgctgc tgccgccgcc agccacgaca agggacccga ggcggaggag ggcgtcgagc 240 tgcaggaagg cggggacggc ccaggagcgg aggagcagac agcggtggcc atcaccagcg 300 tccagcaggc ggcgttcggc gaccacaaca tccagtacca gttccgcaca gagacaaatg 360 gaggacaggt gacataccgc gtagtccagg tgactgatgg tcagctggac ggccagggcg 420 acacagctgg cgccgtcagc gtcgtgtcca ccgctgcctt cgcggggggg cagcaggctg 480 tgacccaggt gggtgtggac ggggcagccc agcgcccggg ccccgccgct gcctctgtgc 540 ccccaggtcc tgcagcgccc ttcccgctgg ctgtgatcca aaatcccttc agcaatggtg 600 gcagtccggc ggccgaggct gtcagcgggg aggcacgatt tgcctatttc ccagcgtcca 660 gtgtgggaga tactacggct gtgtccgtac agaccacaga ccagagcttg caggctggag 720 gccagttcta cgtcatgatg acgccccagg atgtgcttca gacaggaaca cagaggacga 780 tcgccccccg gacacaccct tactctccaa aaattgatgg aaccagaaca ccccgagatg 840 agaggagaag agcccagcac aacgaagtgg agcggaggcg gagggacaag atcaacaact 900 ggatcgtcca gctttcgaaa atcattccag actgtaacgc agacaacagc aagacgggag 960 cgagtaaagg agggatcctg tccaaggcct gcgattacat ccgggagttg cgccagacca 1020 accagcgcat gcaggagacc ttcaaagagg ccgagcggct gcagatggac aacgagctcc 1080 tgaggcagca gatcgaggag ctgaagaatg agaacgccct gcttcgagcc cagctgcagc 1140 agcacaacct ggagatggtg ggcgagggca cccggcagtg acgcccgcca ccaccacgca 1200 gccgccgccg cccacgccgg cctctgctgc ccccttcccc agcccttagc acagagaggg 1260 acacatgccc ctcccccagc tgcgtttttt tatagtagat ttttaacaaa aaacggggag 1320 aaataatgca tttctgtgga tacagtgccc accgccctcc tccacttgga aacggtatcc 1380 tccctgccca tccgtctgtc tgtcgccctt ctcccggccc tcactaagcc ccggcacttc 1440 tagtggtctc acctggaggc aagagggagg ggacagaggc cctgccacgt cccgctgcct 1500 cctgctctct ggaggtactg agacagggtg ctgatgggaa ggaggggagc ctttgggggg 1560 ccacccgggg cctggaccta tgcagggagg ccacgtccca ccccacctct tgtttctggg 1620 tccctgctcc cctttggggg tgtgtgtgtg tgttttaatt ttctttatgg aaaaattgac 1680 aaaaaaaaaa tagagagaga ggtatttaac tgcaataaac tggccccatg tggcccccgc 1740 cttgtc 1746 <![CDATA[<210> 47]]> <![CDATA[<211> 2979]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 47]]> attctcgcta gttcgatcgg tagcgggagc ggagagcgga ccccagagag ccctgagcag 60 ccccaccgcc gccgccggcc tagttaccat cacaccccgg gaggagccgc agctgccgca 120 gccggcccca gtcaccatca ccgcaaccat gagcagcgag gccgagaccc agcagccgcc 180 cgccgccccc cccgccgccc ccgccctcag cgccgccgac accaagcccg gcactacggg 240 cagcggcgca gggagcggtg gcccgggcgg cctcacatcg gcggcgcctg ccggcgggga 300 caagaaggtc atcgcaacga aggttttggg aacagtaaaa tggttcaatg taaggaacgg 360 atatggtttc atcaacagga atgacaccaa ggaagatgta tttgtacacc agactgccat 420 aaagaagaat aaccccagga agtaccttcg cagtgtagga gatggagaga ctgtggagtt 480 tgatgttgtt gaaggagaaa agggtgcgga ggcagcaaat gttacaggtc ctggtggtgt 540 tccagttcaa ggcagtaaat atgcagcaga ccgtaaccat tatagacgct atccacgtcg 600 taggggtcct ccacgcaatt accagcaaaa ttaccagaat agtgagagtg gggaaaagaa 660 cgagggatcg gagagtgctc ccgaaggcca ggcccaacaa cgccggccct accgcaggcg 720 aaggttccca ccttactaca tgcggagacc ctatgggcgt cgaccacagt attccaaccc 780 tcctgtgcag ggagaagtga tggagggtgc tgacaaccag ggtgcaggag aacaaggtag 840 accagtgagg cagaatatgt atcggggata tagaccacga ttccgcaggg gccctcctcg 900 ccaaagacag cctagagagg acggcaatga agaagataaa gaaaatcaag gagatgagac 960 ccaaggtcag cagccacctc aacgtcggta ccgccgcaac ttcaattacc gacgcagacg 1020 cccagaaaac cctaaaccac aagatggcaa agagacaaaa gcagccgatc caccagctga 1080 gaattcgtcc gctcccgagg ctgagcaggg cggggctgag taaatgccgg cttaccatct 1140 ctaccatcat ccggtttagt catccaacaa gaagaaatat gaaattccag caataagaaa 1200 tgaacaaaag attggagctg aagacctaaa gtgcttgctt tttgcccgtt gaccagataa 1260 atagaactat ctgcattatc tatgcagcat ggggttttta ttatttttac ctaaagacgt 1320 ctctttttgg taataacaaa cgtgtttttt aaaaaagcct ggtttttctc aatacgcctt 1380 taaaggtttt taaattgttt catatctggt caagttgaga tttttaagaa cttcattttt 1440 aatttgtaat aaaagtttac aacttgattt tttcaaaaaa gtcaacaaac tgcaagcacc 1500 tgttaataaa ggtcttaaat aattgtcttt gtgtaaattt gtctagtttt gctttagttt 1560 gtaagtattt agctatttat aggaccctta gcttgaccca gtctacaaat agatgatgct 1620 cactggtaat tccctcaggt aaaatgtctc aaaatctcta atcctttaag tggcatgcct 1680 gtgggcccat actaaaaatt agaaaataca tactctgata acctggccat ttttcattga 1740 aggatttagc tcatttgtaa gaaagacttg agtgtagatt ttgggtgggt ccctttggct 1800 gtgaggcatt gtttaaaagg gcattgctct agcctagacc gaccagactc tcatcctgct 1860 ccacttagtt ttgtcacctt gggagaattt gtttcagtgt gtcaattgaa gatgccaatt 1920 gaagtgttag gacaacctgt cacactgcct ggtgtggtca tcaaatattg gttcagctcc 1980 ttatgtccta gagatggaaa caagtaatat aaaacccatg ggaaagctgc ttaggaacat 2040 ggaggttggt gagcttgtaa ttatgtggtt ctcaacacct taaatcctaa gcctagtctg 2100 gctgatcttt tctctttttg agacggagtc ttgttctgtc atcaggctgg agtacagtgg 2160 cacaatcttg gctcactgca acctccacct ctaggtttaa gcgattctcc tgcctcggcc 2220 accttagtag ctgggagtac aggtgcgtgc caccacaccc agctaatttt tgtattttta 2280 atagagatgg ggttgcactg tgttagccag gatggtcttg atctcttgac cttgtgatcc 2340 gcccgcctca gcctcccaaa gtgctgggat tacaggtgtg agccaccgca cctggcctct 2400 ctggcttttg ttttctaatg ttttgttaga tgttctttgg cttgctttgt gaaatagtca 2460 tgtagttgat agtgactgct gccccgaaac actccagatc atcctggcca gctatcaggg 2520 cccaggggaa gcagacagta ggggtcggga gtaggccaga gtggcacatc aggaatcctg 2580 cagtgctgtg gaagtcatct cctgcttggg actaactctt tgcagaggac ttgataagag 2640 actactcaaa aaaaattttt ttaaccctac ttagtgtaaa tatctgtact gcagaagtga 2700 gttagcctat ttcttgctgg tgttcatgaa aatactgtgt tggcaagagt gcagtggacc 2760 tgaaacttca actgttggta gcatctaaac tgttacttac aactgcagac gcacacagtc 2820 cctgacttaa acagtggttt gacttagggg cttttagtgg ggttacggtt tctactgaat 2880 caacattgtt ttcatggcat cacagagttg aaaaatcata aatgaaacca ttgtaagttg 2940 actgcagtgt tgccaacatt aaatgcagtt tcaacttaa 2979 <![CDATA[<210> 48]]> <![CDATA[<211> 13740]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 48]]> gtcggccatt ttgtgtctgc ttcctgtggg acgtggtggt agccgttggg ttgggaaagt 60 gagggatttt tggcctcgtt tctcctgctt cttttctcct cccttttact ttgccggtag 120 aacacagtta tgggtcgcaa gaagaagaag cagctgaagc cgtggtgctg gtattgtaat 180 agagattttg atgatgagaa gatccttatt cagcaccaaa aagcaaagca ttttaaatgc 240 catatatgtc acaagaaatt gtatacagga cctggcttag ctattcattg catgcaggta 300 cataaagaaa caatagatgc cgtaccaaat gcaatacctg gaagaacaga catagagttg 360 gaaatatatg gtatggaagg tattccagaa aaagacatgg atgaaagacg acgacttctt 420 gaacagaaaa cacaagaaag tcaaaaaaag aagcaacaag atgattctga tgaatatgat 480 gatgacgact ctgcagcctc aacttcattt cagccacagc ctgttcaacc tcagcaaggt 540 tatattcctc caatggcaca gccaggactg ccaccagtac caggagcacc aggaatgcct 600 ccaggcatac ctccattaat gccaggtgtt cctcctctga tgccaggaat gccaccagtt 660 atgccaggca tgccacctgg attgcatcat cagagaaaat acacccagtc attttgcggt 720 gaaaacataa tgatgccaat gggtggaatg atgccacctg gaccaggaat accacctctg 780 atgcctggaa tgccaccagg tatgccccca cctgttccac gtcctggaat tcctccaatg 840 actcaagcac aggctgtttc agcgccaggt attcttaata gaccacctgc accaacagca 900 actgtacctg ccccacagcc tccagttact aagcctcttt tccccagtgc tggacagatg 960 gggacacctg tcacaagctc aagtacagct tcatccaatt cagaaagtct gtctgcatct 1020 tctaaagctc tgtttcctag cacagcacaa gctcaggcag ctgtccaagg acctgttggt 1080 acagatttca aacccttaaa tagtacccct gcaacaacta cagaaccccc aaagcctaca 1140 ttccctgctt atacacagtc tacagcttca acaactagta caacaaatag tactgcagct 1200 aaaccagcgg cttcaataac aagtaagcct gctacactta caacaactag tgcaaccagt 1260 aagttgatcc atccagatga ggatatatcc ctggaagaga gaagggcaca gttacctaag 1320 tatcaacgta atcttcctcg gccaggacag gcccccatcg gtaatccacc agttggacca 1380 attggaggta tgatgccacc acagccaggc atcccacagc aacaaggaat gagaccccca 1440 atgccacctc atggtcagta tggtggtcat catcaaggca tgccaggata ccttcctggt 1500 gctatgcccc cgtatgggca gggaccgcca atggtgcccc cttaccaggg tgggcctcct 1560 cgacctccga tgggaatgag acctcctgta atgtcgcaag gtggccgtta ctgatcttac 1620 ttcatccagt ctaataggtt tggagattaa accttttctc aacttgtgct gtttatatag 1680 ccaagcttcc gtcaataagg cttcattgtg actttaacaa acattatctt cccacatacc 1740 aggaactatt ggacatttat tttacatggg aaaaattatt tggaataata aagcaggaac 1800 ttttcctgaa gttgcaattt atactgtatg gcttcttttt catgtttcat ctaggttttt 1860 agaagtgaag tatagtaaat ttggttcgtt aaattgtgaa ggcgctggaa ttacatgaac 1920 ataccaccct agtaaaggca agttctgtaa gcttacattg ctatttgtaa agtttgcctt 1980 cacagcattt cagatgctgt tggacttcat gtccccaacc tagcttggtg agggctgtaa 2040 ctgtttccaa gtacttgtac attggaagtc tgaatgtgta acaatattta atgtatttag 2100 agttcctcat gttgcagggt ttaagaaatc tgacccacca aggtcatgtg acttttctgt 2160 actgttaaac ttcattgtaa taaaatgaga gaaaaattta tgccttttta ttcataaccc 2220 agctgtggac cactgcctga aaggtttgta cagatgcatg ccacagtaga tgtccacata 2280 ataaaattca tagttaccaa tgcagttttg atatatcatt ggattctgtc tttgagttgt 2340 aggttatttc ttagctgcat gttttaaact gaatttgcat agagttgtat gttaatgttt 2400 cagttaagag aaaaacttaa gatacatgag tcattacata atgggtatga aatctttata 2460 atcacccttc caccctctat ggtgtcagta cacatcacgt gtcatagata cttaaaatgt 2520 aaatgttaac acttttcctt cctgctgaga tgtttagagc ctagtgccag acccattcat 2580 ttccttttga ttatttttga gactcagtac tgcatggacc tcagaagctt ttcaggtgca 2640 aacttctaga agcttaggtg catgcagtaa tagcttcttg tgctgttaat gggttattat 2700 atattattct aagtgtaatg ctgagaatct aaatgtgtct ctgttgggat ggttaacaga 2760 tgaattggca atttttatta tgttcctgga agattacatt attcatttga gtaccttctg 2820 ttattaagcc taggtagcct tactgtgcaa ctttttattt atccttggaa attttgaatg 2880 ttgtgttctt acagagagct tttctgtaga gatgactgct attcaatatt ttgtgttgca 2940 acctcttaaa ataatagctc ttgttgacct ttttgggatc tgtttttctg atcttttgca 3000 gggtagtttt atgatttttt aggcatcaaa taacctatgc aaagtattaa tataatgaac 3060 tcaagttgag tttttctcat tataaagtta agacttctaa gaaaatggta acatttcttt 3120 ataactttcc tgtgaaggta tagataaaac acatgaagtc tgaagttgta tggaaaaaag 3180 ggctttaact ttgaaggaaa atatattgaa aagtgattta gccatcacaa aagagttcgt 3240 atttatgtga cagatgaaag tcataccttt aagcaaaaca ttgcaagtat tataaagctg 3300 aatgctattt taactcacat tggctgggtg cagtggctca cgcctgtaat cccagccctc 3360 tggaaggctg agatgggagg attgcttgag tccaggagtt tgagaccagc ctggccaaca 3420 tggcaaaacc ccatctgtac aaaacattta aaaattagcc aggcgcgtta gtgtgtgtct 3480 gtggtcccag ctgctcaaga ggctgaggaa ggaggttctt cctccttccg aggctgcggt 3540 gagctatgtt cactccagcc tgggcaacag agcgagactc tgtcaaaaaa taaattaaaa 3600 tatctgatta tctggcttca atgattttgg ctcctgtgct tgtggtacca tagtggtaca 3660 aaaattttca tagtttgaaa ataaaacagg tattttgcca gtaatgtatt tctttctgcc 3720 agcagccaag tcccaaacca ctttcccctc tgaacctctg cttacctaaa tggtttcaaa 3780 attaatacat gctgctttga tttggcagca cacttaatat actgctgaag gaaaacttgt 3840 gttgaaagtc tttaagataa aaatggtgtg ataggccggg cgcagtggct cacgcctgta 3900 atcccagcac tttgggaggc ccaggcgggt ggatcatgag gtcaggagat ggagaccatc 3960 ctggctaaca cggtgaaacc ccgtttctac taaaaataca aaaaattagc tgggcgtagt 4020 tgcggatgcc tgtagtccca actactctgg agaccgaggc aggagaatgg cgtgaacccg 4080 ggaggcatag cttgcagtga gcggagatca caccactgca ctctagcctg gacgacagat 4140 tgagactccg tctcaaaaaa aaaaaatgct gtgattaaat ttagaataat taagtaaggg 4200 gtgctctccc aaattctcag gaatttcatg tatacggtta ttgacaaact gcaatagggt 4260 tagtagacct gtttcagaaa ttatgtgaag ctttatttgc attttatgca aagaaggttg 4320 atactttgta gcaaggtttt ttgctctctg tataggtctg atgggcaaaa atggaacttt 4380 taaatatggg atagaattct aattaaaaat taattgaaag tgttaggcat tggcagataa 4440 aacttaagct catgagttcc tgagtttgta gctataggct cagaggtggt gtacccattt 4500 aatatatttg aagtgtaatt tttgcatgca tccaaacgta attaagcttc tagaaaatac 4560 cttttttcta aatgcttctg gggtccatag tgtggttgaa ttatgagtgg agcaaattat 4620 attcatataa ttaactctga ctcaaccttc cttaagtagt agatgaagtt gagtcaaagt 4680 ggatgccaac tgccctcaca gaagacaact tttgggactt gataattcag gcaggcattg 4740 tgattgtcat aattaaggaa gctgtaaggt tagtagggct ggcaactttg gctctacctt 4800 acatccaccc cttttagaaa aacaagaaaa cattttgtct ggcactagtt tctgttgtat 4860 aagttttcat actgtttaac aagaccacag caggtaagga ttaatttttg agtggctgct 4920 ggaattactt gatttgaata cttagtattt tagtagtgtc tcacacattt gccattaggt 4980 atgaataaaa tattcctact gtactcctat tccactaagt tacattttga acttagactc 5040 accttaatta aacttaatta attggggagg gggattcccc aacaaaaaga agtacgggct 5100 cagagtggaa ttgtagtgga caatagttaa aaacaaagct gctccttttg cttgcttgat 5160 cattgggatt tttaaaaaaa aaaattttaa tgcatgtctt ttaaattaat tgggaactgt 5220 ttttctaaaa ttaaaatttt cttcttccta tagccctgcc ataggacagg ctgaggctga 5280 gtctcagtgt tgccctgttc agtctgaggc aagtgggatt tattttattc cttatagggg 5340 ctttcacagc tttatggctg ttggatattt atgtccccaa acttgcagca agtttggtga 5400 aggcccctaa atttaattaa acttaggatt tttatactct tttggcagag aaggctctat 5460 attaatattc acgtttgact gtggtgttaa taaacataag tatttcatat gcaattttat 5520 gtaatttgct gtgtgttaca taattaacag cttcagtaaa gcttgtgttc ctatattgaa 5580 cttcaataaa ttgacaaaat ttgatatttt tgattggagg caagaaatgt ttcattcaag 5640 ttttttactt tcacttctag gaaaatctta ctggttttat tttctccata aactattaaa 5700 tttaacctca aggataagtt taatcattgg aaatgccact ggatactgaa atgtgccttc 5760 tcttttttga gacggagttt cactcttatc acccaggatg gagtgcagtg gtgcgatctc 5820 ggttcactgc aacctctgcc tcccggattc aagtgattct cctgcctcag cctcccgagt 5880 agctgggatt ataggctccc gccaccacat ctggctattt tttcaatatt tttcagtagg 5940 gatggggttt tgccgtgttg gccaggctgg tctcaaactc ctgacctcag gtgatccacc 6000 catctcagcc tcccagagtg ctggagtagc aggtgtgagc caccgcgcct ggccaaaatc 6060 tgcattcttt tttttttttt tttttttttt ttgagactgt ctcgctgtgt cacccaggcc 6120 agagtgcagt agcacgatct cagctcacta caacctccac ctcctggatt caagcgattc 6180 tcctgtctca gcctcccgag tagctgggac tacaggtgct tgccaccaca cccggctaat 6240 tttttgtatt tttagtagag acggggtttc accgtgttag ccaggatggt ctcgatctcc 6300 tgactttgcg atccccctgc ctcggcctcc caaagtgctg ggattacagg cgtgggccac 6360 cgcgcttggc caaaatctgc attcttaatc acaaacttac gcattgaatg ttaaggctaa 6420 aaggtcatct ggaaatgctt aattttaaaa tattttcaag cctcaccaca ttagagcaaa 6480 tgttaatgta gagccctgta aaggtgggaa ggtggtgtct atgtgtgtgc ttgtgtatgt 6540 gggggtatag accatatagt tgatataaca acagaatttg ggtgttacag acctttcagc 6600 atggatggat tactaatttt caggtatcga aactgaaatt tgatacctga tcctgtggta 6660 aagtatgtta aactatggtt ttggagtgat tattttgagg ttcattttca gcctcactga 6720 acagtgtttt acgcacatgt gaaaagtatc cacatttgtt tccaactaaa atttgctttt 6780 atttggtgag aaaagttgtg tgcgtgtgtt tgttgtaggg aataattagg gaattggaag 6840 agaggccaaa aacaaacctg aattactttt gtttcttgtg tttgagccac gattctatcc 6900 agatagcagt ttactctgag cagtaacaat gaacaagcag tatagcattt agcaaacctg 6960 gaattgtttg tatatggttt tcattcttgg aagcataaag aaaaaatatg cattaaatga 7020 attgtaaatt ttgacttgtt aaataacatg tttttcacta taactaatag gattttaata 7080 tttaaagaat tttgttgctt ccatgacaaa atatcccatt ggactatttt ataacctcag 7140 taatcaacat ttaagagtcc ttaattggag atctgttttc tctattacct accatcctgc 7200 aatatgctga aatctttcta agttgcttat cttaattcta atggtgataa ttgaaaaaag 7260 tgtgctggaa atacaggctc ttatctggtt gagtactggg ggtgggaagg atttagtaat 7320 gtcataatct gttgaaggta atatctatag ataactaaga tagttccttt ttttttgtag 7380 ttctgtgact cagacaaata agattttgag aattatgtag tttttaggtg tctgtaacat 7440 ccactagtaa aacttggcaa atgaaagaaa attgtgaagt caccacttta actgagtcaa 7500 aattttgttt gaataagctg atgaaaatag acatgtaccc tagaagtaga tactctaaaa 7560 ttatacagac atgaatgtct tttttaaaag gttgtcatta ttgacctaat attgagtaat 7620 ctttctgcgt tattccaaat tgaaatttgt ttgctcttca ttgtaacttt tatgtaaaag 7680 tcctttaaaa ggggattcaa ttataaggct atttgactat agggcagatt tttataagta 7740 aacattcccc caattccact tatgctaact gtctcatgac agtaaagttt actccttttt 7800 agaaaccctt tctcagtatt ttaatttctg tcattgaatc atttaaataa taaccttttg 7860 tttttatagc aaagaaatca tctgactttt ctgtgtgatg tttcttggca aaataagcac 7920 ttgatgtatg gtcatgtaca taatggatat tcattaattt tgtgattagt gctgagtttt 7980 ctaaactact atcttaagct cttaggcacc ctattatgga tctaattcaa accaatatgt 8040 aggaaatgga gaaagtagga cttcagtttg cgcttcccaa taactttaaa tatatccacc 8100 ttttccaagt gtttaagccc taaaacatct atctttattt ttttacctgg catttttgtt 8160 agaaaataga ttacgtttta aagtaacatt aaaaaaattc ttcagtaaga taattgcttt 8220 taataagtat atttttcttg ctcttggctc tatacatttt tgcataatat tttagtcttg 8280 aaaagctttt cattttctta actctggaaa ataatagttt ggaactaaat tagtttgaga 8340 aatctgaatc atctctcttt aaatctgttc agttagtctc atgtattctc aggggaaaat 8400 gtctttattt tactaagcgg aagtagtagt catattgagg cagaaatttg tagcccaaac 8460 aaggtaggtc ttcgctgaaa ctaatttgaa ctattcctat ttgaagcaaa ttgaacacta 8520 ttataaatct agactggcta attagatgga aactttgatg gttaggttct ttaagaggca 8580 tacaatccgt tatgagaatg tttatgttta tgttttaatt tttatcaaaa taacctcaga 8640 ggaggtacat gtgagtaaac tgtcttaatg gttgattact tggaacccac ccattaattc 8700 taaatgatgt aatggtctat aaggtagtaa tctggcacag cttcagtaat gtgtgctgtg 8760 tttgtaaaaa ggtgaagtac tttattggca ttttctaagc cctctgacat tgttagtgtc 8820 tgggttggtt ggtttgcatt ttactattat ggtggaatct gtgttccttc accattggtt 8880 aagtctgagg aactaacagt gaaattcatt gatggccaac ttggataaaa atgaagaatg 8940 atattttccc agtttactac acatggacca atagtgatta tttgggagag aacactgggt 9000 agtattgttt gacttaagaa ccttaaatat attgaaaagt aatggcattc ttgctcatga 9060 tttgcatttg ttagtgaggt ctcaccatag tattttaatg tagcttctta ttaaaatttt 9120 attcataaat agtttagcag tcacagaggt gaaaaaaaaa agatttgcac catcatatcc 9180 gagtctttac taataaaatg aggctgctta agtacccaag tggagcaagg gaagagttac 9240 tacagttact gtaagtctga gttagaaaaa atacagagca tctagttatt gagcaaagcc 9300 cccttttacc tgttcgctta ttcaaagaga aacaatagaa tttgcttctc agtacatgtt 9360 tttaaaattg agaatctctg atgtgacaaa atcaattttt acaaaagttg aattaaaaac 9420 ttttaaaaat tgcttgtctt tgggggtatg tctacatatt cgtttaaatt tagaaattcc 9480 cacatgttta agatatatgc ccatcccctt tttagagtaa tcaaaatttc tatcacagtt 9540 cacatactgg aatacatagt aaaattgaga tgtgtccaag agattttcaa tgttaattag 9600 ctcattctaa atagccaata taaggtaact tctgtttaaa aaaaaaaaaa actagggaaa 9660 agttttaaat gtattagtat caggctctga ggaaatttaa tgcacattga ctttttaaac 9720 tatggattga actcctcagt ttaatacaat ttgtgttttt gttaactagc agcagaattt 9780 cagcatttgc tacttactgg tagagaagaa aaatcccaca gccctgccag tacaggttag 9840 tttaatctgt aagtacctga tgttcctatt tttttcaaac atatccatat aactcacaca 9900 aggaagaaag ctgtgcggtt acttaaatgt tagtataact aataatagat ccattggaca 9960 ctttaaacac tcagtacttg ggccaaagta gatctaggtt tgctaacccc agttgtaata 10020 aaggtgtaat actgctcctt tgttatctcc ttgtggttca acctaagtag atacattgta 10080 cataaaagga aaagacagtt tcagttggct atgcccttgt tgatagatga tatggagtcc 10140 agggctttgg gtccagggtc ttttacttaa gctatttcat ggtggttctc tcattcacct 10200 tttaactttt tacattatga atcaacctaa gaaaaaaggc aagtttcctc acatctagaa 10260 atgataaatg gtgtacagtc ataagctaga atatgttttt ataatgcttt tttgttcttt 10320 tagcaacact tgtaaataca agtactcctc tatttttgtt ctttttttgt aaactataac 10380 gtatcccgtt ggtgtaccag tgagttcatt ttactgtaaa ctaagaataa catacctttt 10440 taatactgaa agttgactac tcatcaagaa atgtagctag attctttatg taacactttt 10500 gaggggcagt ggggacataa tgggttgtgg aaaatgtgtt ttaacatttt tatttttttt 10560 ttattctacc cgagttcatt gttgtttgaa ccatcctcta aagatttcct ttaacctcta 10620 aatgttgtgc ttttaggttg ataacaaatg taaagcactg aggagggagg aataaagcat 10680 acaagttaat ttctaatttt cgcaagcctg aaccatccta atctgatagt aggatgtatg 10740 gcttcttcct tttcaccttg tgtgatgttt aatttgagac gatctagcca taaaactagt 10800 aatcttgaat tcctcttgag ctggatggtg attagccatt gtgaaaacag attatatgga 10860 aattgtgcat attgctaaat tttaaaacat ggatttatca actgataata aaatatatct 10920 tacaagataa ccacttgttt tttaatgtaa aattgcacaa gggcttaagt ttcattgcct 10980 ttcacagttt aatctgtata tgaaatggtg tagatacagt ggaaatggtt ttccttaaaa 11040 ccatctcttt aaagctgcct ttctggtgag tactgtttta tacttttata tattataatt 11100 ttatcttcta aaattaactg aaataggaca ctttgattaa agaggtgagc actctgaatt 11160 tctacatctt tggatattac ttgaatcaag aatattagaa aattatttta ccacctggca 11220 tttccctttt aatttgctag ttcacttttt tctgaccttc acttaacaga ctataaatac 11280 aaaaactttg aacacataaa ttatttcatt ttggtgagat ggaataaatg tttaaaatta 11340 gtatttaaga aagttcttaa acattttttt tagttggcag ccaaaagatt tttcttagtg 11400 ctttggagac attgcatagg tgtaaaatta agataccaga acttcattct gttcttgttg 11460 aagctgttgt tgtggtgatt catgagcagt aagctggagt tagagtggaa gaagggttta 11520 ccaaaattct tcctgcagac tagttgctta cagggtttct ttgagaggct taaaaatttc 11580 aaaagtatta tttaagccac tctaaccctg catgaaaaat tggagttaga aatactgatt 11640 tctgagacca cgtataccag tgaaaattag cttctgagta aatttctaat ttatgccctg 11700 ctttatttag cctcgctata tgtaacacat ggattatttt ttccctctag tttttaacta 11760 tatcctagat taaaaccagc atatgctaag aatgttttta cattctgttt cctcctgtga 11820 tctttctgaa ccaataataa acagtcaact gtgatgcttt ttagtatgaa caatgatagt 11880 tttctaaaat ctgaaaatca atacctgagt atgtgatgtg gcaatgcatt cttctagata 11940 agcactaaac aaagtatgga ccctcaattt atgtctttaa gatttaaagt gaagtaaatt 12000 tctaaggaac tgtgtccttt cctagcagga ataaacagtg aaaatttggt aagtatttaa 12060 cttgaagtgc atgtaatagt gatgagagta agtagccaaa tttccgtaat ataaggtaat 12120 gtttaaaagt gagcaataat tattgcatct cttttgcgac ttcatgtaga tgtgattaac 12180 attttttaca aatttgcctg cataaagatt aaattggaac ataccttact cctttgtctg 12240 gtttttttat tttgtatggt gctttaaata ctaattttat atttcaagct ttttgcaggg 12300 tagaaataag tggctgttaa agaaaatatc ttcaagaagg attatttcag tgtccctttt 12360 taaaactcga tgatggcttt cagtttattt aagtcttctg tttttcagct ccagttaaaa 12420 ctgacaatag gcagctatca aaaatggaaa aaatcttgtg ctctttctgg aatattagag 12480 gaatcagtta ataatagtaa agtggtatta acccaatact tgatttgcag tttttaaagc 12540 agtttttaaa ttgagagaaa aggggctggg cccagctgag gcgggtggat ctcctgaggt 12600 caggagtttg agaccagcct ggccaacata gtgaaacccc gtctctacta aaaatacaaa 12660 aatcagccgg gtgtggtggg acgtgcctgt aaccccagct actctggagg ctgaggcagg 12720 aaaatcgctt gaacccaggg ggaggaggtt gcagtgagcc gagatggcgc cgttgcactc 12780 cagcttgggt gacagagcga gactccgtct caaaaaaaaa aagaaaaaaa gaaaaagtga 12840 taagatttgg gagtctattc cctgggatgt tctattaata ataaagtgat aataaatgaa 12900 ggttaaagtc aagtgttcaa ttactacacc aggaaagatt gattatttct gaggaaaagg 12960 tccatttatt tccaaactag tctgtagtgg tttagagtaa gcattatttt atgaagtggt 13020 acaagattgc aaaggttagt aaagggacct gtctgtcagg tcaatcttcg gtcttcactt 13080 ttactggcaa gggattatgt gaagagtaag tcatacaagg gatatgattg taaggaggtc 13140 ctgaacaaag catgataaat gttagtccat gtgtattatt aaatggtcta aagaaaaatc 13200 atgactgatc gcataatttt taatgtaagt aaatgagctc actaagggta attaaatact 13260 agcttttaaa atttaaagtt ctcacgaata ttagtgcatc ttgtcacttt gatttgtcac 13320 ctggttaaat agctggaagc ttgtgcaaat gaaaaatgaa atggaagact acatttgtat 13380 atatatctgt ataatttttg tttactagta ggttcagaga gagatctgag atgttcctta 13440 acatgtagcc atgtaattag aactcacaag gggcattgaa atgtttttct ttttcagata 13500 gtctggggct atttacttat tttaagtaag ccaagtctac catttgaaaa atggtgcttt 13560 atttccatat ctgaagcctg aagttatttt ttagtttgtt ttcatctaaa agtggaaaga 13620 tttttgcttc tgcgttatta agagcctctt tgtttggagg agatggttat ctccttcact 13680 cattaacctt tgagtgcttg ttatctacaa agatgaataa aatctttcat ttattattta 13740 <![CDATA[<210> 49]]> <![CDATA[<211> 1968]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 49]]> ccctctcgct ccccgggagc gcctggcggg gccgctgggc cgagggggcc gccggcgggg 60 ctggcgggcg gggggcttcc tgcgggcccg gggggagccg gcggccggcg cgggcgcggc 120 gggccgggca ggggcgaggg gcgccgggtc ttgccccaga agctgcgggc acatccacgc 180 ctgaaatgcg gcgctcagtc ctggtcagga acccaggcca caaaggcctg agacccgttt 240 atgaagagct cgactctgac tccgaggacc tagaccccaa tcctgaagat ctggacccgg 300 tttctgaaga cccagagcct gatcctgaag acctcaacac tgtcccggaa gacgtggacc 360 ccagctatga agatctggag cccgtctcgg aggatctgga ccccgacgcc gaagctccgg 420 gctcggaacc ccaagatccc gaccccatgt cttcgagttt cgacctcgat ccagatgtga 480 ttggccccgt acccctgatt ctcgatccta acagcgacac cctcagcccc ggcgatccaa 540 aagtggaccc catctcctct ggcctcactg ccacccccca ggtcttggcc accagccccg 600 cggtgctccc cgcccccgcc agcccgcccc ggcccttctc ctgcccggat tgcgggcgag 660 ccttccgccg cagctccggg ctgagccagc atcgccgcac gcacagcggc gagaagccgt 720 accgctgccc cgactgcggg aagtccttca gccacggtgc caccctggct cagcaccgtg 780 gcatccacac tggggcgcgg ccgtaccagt gcgcggcctg cggcaaggcc ttcggctggc 840 gctccacgct gctgaaacat cgcagcagcc acagcgggga gaagccgcac cactgcccgg 900 tgtgtggcaa ggccttcggg cacggctcgc tcctggcaca gcacctgcgc acgcacggcg 960 gcccgcggcc ccacaagtgc ccggtgtgcg ccaagggctt cggccagggc tctgcgctgc 1020 tcaaacacct gcgcacgcac acgggcgagc ggccctaccc gtgtccgcag tgcggcaagg 1080 ccttcgggca gagctcggcg ctgctgcagc accagcgcac acacacggcc gagcgcccct 1140 accgctgccc ccactgcggc aaagccttcg ggcagagctc caacttgcaa caccacctgc 1200 gcatccacac gggcgagcgg ccctacgcct gcccgcactg ctccaaggcc ttcggccaga 1260 gctcagcgct gctccagcac ctgcacgtgc attcgggcga gcgtccctat cgctgtcagc 1320 tctgcgggaa ggccttcggc caggcctcca gcctcaccaa gcacaaacgg gtgcatgagg 1380 gtgcagccgc tgctgcagct gccgcggccg ctgcagctgc agcagcggcc gccggcctgg 1440 gcctcgggcc tggcctaagc cctgcatcca tgatgaggcc ggggcaggtc tccctcctgg 1500 gtcctgatgc tgtttctgtg ctcggctctg gcttgggcct cagccctggc accagctctg 1560 gccgcaaccc tgaccctggc tctgggccgg gcactctgcc ggatcccagc tccaaacccc 1620 tccccggctc cagatccacc cccagcccta ctcctgtgga atcttctgac ccaaaggctg 1680 ggcacgacgc tggtcccgac cttgtgccca gcccagacct tgatcctgtg cccagcccag 1740 accctgatcc tgtgcccagc cctgatccca accctgtgtc ctgccctgac ccctgttctc 1800 ccactcgtgg cactgtcagc ccagccctcc ctaccggcga gagtccagag tgggtacagg 1860 agcaaggggc actgctgggg cctgatggct gaaggagacg ccggcatcct cgggggcctg 1920 gggaagttgt gtgttgtgca gtcagtaaaa tcctcccact gcctccgg 1968 <![CDATA[<210> 50]]> <![CDATA[<211> 4797]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 50]]> aagtgcgcat gtgcgcgagg agtcgctcgg gcacttattg agcgccgact gtctacgggc 60 ggccgggggt gatgggcaga ggcttcagtg tccccttcgc ctccgcagga gaggagaggc 120 agcagcatgg cgagtgtcct gtcccgacgc cttggaaagc ggtccctcct gggagcccgg 180 gtgttgggac ccagtgcctc ggaggggccc tcggctgccc caccctcgga gccactgcta 240 gaaggggccg ctccccagcc tttcaccacc tctgatgaca ccccctgcca ggagcagccc 300 aaggaagtcc ttaaggctcc cagcacctcg ggccttcagc aggtggcctt tcagcctggg 360 cagaaggttt atgtgtggta cgggggtcaa gagtgcacag gactggtgga gcagcacagc 420 tggatggagg gtcaggtgac cgtctggctg ctggagcaga agctgcaggt ctgctgcagg 480 gtggaggagg tgtggctggc agagctgcag ggcccctgtc cccaggcacc acccctggag 540 cccggagccc aggccctggc ctacaggccc gtctccagga acatcgatgt cccaaagagg 600 aagtcggacg cagtggaaat ggatgagatg atggcggcca tggtgctgac gtccctgtcc 660 tgcagccctg ttgtacagag tcctcccggg accgaggcca acttctctgc ttcccgtgcg 720 gcctgcgacc catggaagga gagtggtgac atctcggaca gcggcagcag cactaccagc 780 ggtcactgga gtgggagcag tggtgtctcc accccctcgc ccccccaccc ccaggccagc 840 cccaagtatt tgggggatgc ttttggttct ccccaaactg atcatggctt tgagaccgat 900 cctgaccctt tcctgctgga cgaaccagct ccacgaaaaa gaaagaactc tgtgaaggtg 960 atgtacaagt gcctgtggcc aaactgtggc aaagttctgc gctccattgt gggcatcaaa 1020 cgacacgtca aagccctcca tctgggggac acagtggact ctgatcagtt caagcgggag 1080 gaggatttct actacacaga ggtgcagctg aaggaggaat ctgctgctgc tgctgctgct 1140 gctgccgcag gcaccccagt ccctgggact cccacctccg agccagctcc cacccccagc 1200 atgactggcc tgcctctgtc tgctcttcca ccacctctgc acaaagccca gtcctccggc 1260 ccagaacatc ctggcccgga gtcctccctg ccctcagggg ctctcagcaa gtcagctcct 1320 gggtccttct ggcacattca ggcagatcat gcataccagg ctctgccatc cttccagatc 1380 ccagtctcac cacacatcta caccagtgtc agctgggctg ctgccccctc cgccgcctgc 1440 tctctctctc cggtccggag ccggtcgcta agcttcagcg agccccagca gccagcacct 1500 gcgatgaaat ctcatctgat cgtcacttct ccaccccggg cccagagtgg tgccaggaaa 1560 gcccgagggg aggctaagaa gtgccgcaag gtgtatggca tcgagcaccg ggaccagtgg 1620 tgcacggcct gccggtggaa gaaggcctgc cagcgctttc tggactgagc tgtgctgcag 1680 gttctactct gttcctggcc ctgccggcag ccactgacaa gaggccagtg tgtcaccagc 1740 cctcagcaga aaccgaaaga gaaagaacgg aaacacggag tttgggctct gttggctaag 1800 gtgtaacact taaagcaatt ttctcccatt gtgcgaacat tttatttttt aaaaaaaaga 1860 aacaaaaata tttttccccc taaaatagga gagagccaaa actgaccaag gctattcagc 1920 agtgaaccag tgaccaaaga attaattacc ctccgtttcc cacatcccca ctctctaggg 1980 gattagcttg tgcgtgtcaa aagaaggaac agctcgttct gcttcctgct gagtcggtga 2040 attctttgct ttctaaactc ttccagaaag gactgtgagc aagatgaatt tacttttctt 2100 aaaaaaaaaa aaaaaaaaaa aaaaaaagag tttctggctg atgggtgact cagagtgcag 2160 gactgcctgg ccgtggggca gaggggtttg cccttctcgg agggtacctc ctgttccctg 2220 tctgagcatc ctgcatggaa gtcaaaggaa atccctttct tggtgacgac ttaaatctgg 2280 gttccctcag acattgggtt gcaccccaac aaatattaaa tggcttcttc ttaaagccca 2340 gagaaagagg ttttttaaaa gactgtcgcc aaatagctga gccaaaaggc tgatcagaat 2400 tcactttttg gaatgtggca gttaaacact accttgatca ttctctcctc tttcctcgag 2460 gaactcctgg agggtttgag cgtctggaaa ctctctgctc tgacccgagg aagcaccctc 2520 ctgacgccgc cttcctccgg ttattgaaag gacgcctcag aaatgctttg ttttctttta 2580 cgatgtattc agaagccttt actgattaaa gttttctttt atttgggtgg ccgggagaga 2640 cccagggagg ttctggaggt tcctttctgt ctcctggccc caccagggat ttccccattt 2700 ctgtttgctg cctgaaagca ggatgaggaa ggccaaggag agtccttgca cccgtgagcg 2760 tcaggatgag gaaatgacag gaggaagacg tgggtttggg ttagtggctg ctggcgtttt 2820 ggcccttggt gtttctggag cctccaggga tctaggggag cctgggctgc gtgcatgtcg 2880 ataagcagag ctgttcttgg ggagaaggag ggaggtctcg ggagtgtagc accatgccaa 2940 ccagccctgc gcgaagacag agtgagccac gcccggatgg cagggcatgt ttctgttttg 3000 gtgtctcact ttcctcccag cgtgacttat ttggggattc ctcagggcct actggaatgt 3060 gactgcccac tgcccagctg cctcgggtac aagtcctggc cctatgtccc agctgtcagg 3120 ggctcaggga atcctaccca gccacctgtc ctgggatgga gtgtcagcat ccaccccttg 3180 gttgtcatcg aggccgccct cccagtcctg ggtgaagata tttgggccac cagggctccc 3240 ttggcccctt cacgtaggaa atagacacgt gctttttaat gcaggacact ttgagtgtta 3300 caaaatctgt agacctggca gtagggtcat gatgttggga agggtgtagt gccctaggtt 3360 ggtgacagaa gggacagaca cttgtgcaca ggtgtctttg gtgatggggt tttttttttt 3420 ataacttagt aaaaaaaaaa aaatgtatgt ggaattctgt ctcttggtaa agctcaaagc 3480 caggctagcc tgaggtggcg cagggctctc cttcctgtcc cttcgatctc cttgagaatt 3540 aagagctggc agctgctgat ggtgtttccc aacccccctc acttcccaag acaaccccca 3600 gcttcaggtc ctcatgggga ggggagggca cgttcttgac acatgggaac ttcgctcagg 3660 agggcctccc cttcccctct ccctcagagt tttcactgcc gtctcgtctt tagaaagctg 3720 tttgaattcc ccccgccccc agtttggacc gtgtagatat aactggatat acggattttt 3780 ctctttgtgc aggcttctta tgccgttggt atacagggca ggaaagagag gaataaaggg 3840 agagagcagt gtggaaacca cggtggtttt gctttgttct tactaggttt tggtgccacc 3900 ttccctgcct gcgcttgtgc cccctctcct ccttggcact ggcggcctcc ttgcctccct 3960 tccacccgtg ctgccatccc gtgcctgtcg tgttggttct tcacacgtgc tctgttctcg 4020 gggttgttcc attcatgcct tcttggaggg tgagggtggc ttgggaaccg acccagtgat 4080 catgcctact ttcttctttg tatctccctc cttcccagcc cacccgggca gcagactctg 4140 atggaaggaa ggtgccgtag gtgggctttt agaaactaac gggactggtt ttcaaagcag 4200 ttatcttggg aaactgttta ttccagcgat gtgacttttt tcagaatatt tcttggaatc 4260 atattcagag tctggggctg tgtgttgagc agccttaagg atgctagaca ctcatttagt 4320 gcccagggag tccagcgaat gacgtctgtg gccaagcgag gtctcaggtg caaagcaaaa 4380 ggaccattta aagtaaaata gcttggattc aatcatgtga cttttaaatt ggctcagaaa 4440 gcaattttgt aatttcagag agtgttttga gccatggcca cgttgtcatt gtgagtctat 4500 agcttgactc cttggagaac aatattcatt tggttgtgga gactgatttg ctgggagaaa 4560 tctgtcctgt tactttctgg tcatcccagg ttctgacttt taccaggggc aaaaaaaaaa 4620 aaagcaagag ggagataaat cccatctgtg agtttgtctt attggcgcct ttttcctcag 4680 ctgtcttcca agtattattt ttactgttaa aaaatttttt aaaaatgtga aatgtaatgt 4740 ttttacagca acaatatgaa atatatttta taaggaataa aatggtacct tgtctga 4797 <![CDATA[<210> 51]]> <![CDATA[<211> 271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 51]]> Met Glu Thr Asn Cys Arg Lys Leu Val Ser Ala Cys Val Gln Leu Glu 1 5 10 15 Lys Asp Lys Ser Gln Gln Gly Lys Asn Glu Asp Val Gly Ala Glu Asp 20 25 30 Pro Ser Lys Lys Lys Arg Gln Arg Arg Gln Arg Thr His Phe Thr Ser 35 40 45 Gln Gln Leu Gln Glu Leu Glu Ala Thr Phe Gln Arg Asn Arg Tyr Pro 50 55 60 Asp Met Ser Thr Arg Glu Glu Ile Ala Val Trp Thr Asn Leu Thr Glu 65 70 75 80 Ala Arg Val Arg Val Trp Phe Lys Asn Arg Arg Ala Lys Trp Arg Lys 85 90 95 Arg Glu Arg Asn Gln Gln Ala Glu Leu Cys Lys Asn Gly Phe Gly Pro 100 105 110 Gln Phe Asn Gly Leu Met Gln Pro Tyr Asp Asp Met Tyr Pro Gly Tyr 115 120 125 Ser Tyr Asn Asn Trp Ala Ala Lys Gly Leu Thr Ser Ala Ser Leu Ser 130 135 140 Thr Lys Ser Phe Pro Phe Phe Asn Ser Met Asn Val Asn Pro Leu Ser 145 150 155 160 Ser Gln Ser Met Phe Ser Pro Pro Asn Ser Ile Ser Ser Met Ser Met 165 170 175 Ser Ser Ser Met Val Pro Ser Ala Val Thr Gly Val Pro Gly Ser Ser 180 185 190 Leu Asn Ser Leu Asn Asn Leu Asn Asn Leu Ser Ser Pro Ser Leu Asn 195 200 205 Ser Ala Val Pro Thr Pro Ala Cys Pro Tyr Ala Pro Pro Thr Pro Pro 210 215 220 Tyr Val Tyr Arg Asp Thr Cys Asn Ser Ser Leu Ala Ser Leu Arg Leu 225 230 235 240 Lys Ala Lys Gln His Ser Ser Phe Gly Tyr Ala Ser Val Gln Asn Pro 245 250 255 Ala Ser Asn Leu Ser Ala Cys Gln Tyr Ala Val Asp Arg Pro Val 260 265 270 <![CDATA[<210> 52]]> <![CDATA[<211> 317]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 52]]> Met Glu Thr Asn Cys Arg Lys Leu Val Ser Ala Cys Val Gln Leu Gly 1 5 10 15 Val Gln Pro Ala Ala Val Glu Cys Leu Phe Ser Lys Asp Ser Glu Ile 20 25 30 Lys Lys Val Glu Phe Thr Asp Ser Pro Glu Ser Arg Lys Glu Ala Ala 35 40 45 Ser Ser Lys Phe Phe Pro Arg Gln His Pro Gly Ala Asn Glu Lys Asp 50 55 60 Lys Ser Gln Gln Gly Lys Asn Glu Asp Val Gly Ala Glu Asp Pro Ser 65 70 75 80 Lys Lys Lys Arg Gln Arg Arg Gln Arg Thr His Phe Thr Ser Gln Gln 85 90 95 Leu Gln Glu Leu Glu Ala Thr Phe Gln Arg Asn Arg Tyr Pro Asp Met 100 105 110 Ser Thr Arg Glu Glu Ile Ala Val Trp Thr Asn Leu Thr Glu Ala Arg 115 120 125 Val Arg Val Trp Phe Lys Asn Arg Arg Ala Lys Trp Arg Lys Arg Glu 130 135 140 Arg Asn Gln Gln Ala Glu Leu Cys Lys Asn Gly Phe Gly Pro Gln Phe 145 150 155 160 Asn Gly Leu Met Gln Pro Tyr Asp Asp Met Tyr Pro Gly Tyr Ser Tyr 165 170 175 Asn Asn Trp Ala Ala Lys Gly Leu Thr Ser Ala Ser Leu Ser Thr Lys 180 185 190 Ser Phe Pro Phe Phe Asn Ser Met Asn Val Asn Pro Leu Ser Ser Gln 195 200 205 Ser Met Phe Ser Pro Pro Asn Ser Ile Ser Ser Met Ser Met Ser Ser 210 215 220 Ser Met Val Pro Ser Ala Val Thr Gly Val Pro Gly Ser Ser Leu Asn 225 230 235 240 Ser Leu Asn Asn Leu Asn Asn Leu Ser Ser Pro Ser Leu Asn Ser Ala 245 250 255 Val Pro Thr Pro Ala Cys Pro Tyr Ala Pro Pro Thr Pro Pro Tyr Val 260 265 270 Tyr Arg Asp Thr Cys Asn Ser Ser Leu Ala Ser Leu Arg Leu Lys Ala 275 280 285 Lys Gln His Ser Ser Phe Gly Tyr Ala Ser Val Gln Asn Pro Ala Ser 290 295 300 Asn Leu Ser Ala Cys Gln Tyr Ala Val Asp Arg Pro Val 305 310 315 <![CDATA[<210> 53]]> <![CDATA[<211> 324]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 53]]> Met Asn Cys Met Lys Gly Pro Leu His Leu Glu His Arg Ala Ala Gly 1 5 10 15 Thr Lys Leu Ser Ala Val Ser Ser Ser Ser Cys His His Pro Gln Pro 20 25 30 Leu Ala Met Ala Ser Val Leu Ala Pro Gly Gln Pro Arg Ser Leu Asp 35 40 45 Ser Ser Lys His Arg Leu Glu Val His Thr Ile Ser Asp Thr Ser Ser 50 55 60 Pro Glu Ala Ala Glu Lys Asp Lys Ser Gln Gln Gly Lys Asn Glu Asp 65 70 75 80 Val Gly Ala Glu Asp Pro Ser Lys Lys Lys Arg Gln Arg Arg Gln Arg 85 90 95 Thr His Phe Thr Ser Gln Gln Leu Gln Glu Leu Glu Ala Thr Phe Gln 100 105 110 Arg Asn Arg Tyr Pro Asp Met Ser Thr Arg Glu Glu Ile Ala Val Trp 115 120 125 Thr Asn Leu Thr Glu Ala Arg Val Arg Val Trp Phe Lys Asn Arg Arg 130 135 140 Ala Lys Trp Arg Lys Arg Glu Arg Asn Gln Gln Ala Glu Leu Cys Lys 145 150 155 160 Asn Gly Phe Gly Pro Gln Phe Asn Gly Leu Met Gln Pro Tyr Asp Asp 165 170 175 Met Tyr Pro Gly Tyr Ser Tyr Asn Asn Trp Ala Ala Lys Gly Leu Thr 180 185 190 Ser Ala Ser Leu Ser Thr Lys Ser Phe Pro Phe Phe Asn Ser Met Asn 195 200 205 Val Asn Pro Leu Ser Ser Gln Ser Met Phe Ser Pro Pro Asn Ser Ile 210 215 220 Ser Ser Met Ser Met Ser Ser Ser Met Val Pro Ser Ala Val Thr Gly 225 230 235 240 Val Pro Gly Ser Ser Leu Asn Ser Leu Asn Asn Leu Asn Asn Leu Ser 245 250 255 Ser Pro Ser Leu Asn Ser Ala Val Pro Thr Pro Ala Cys Pro Tyr Ala 260 265 270 Pro Pro Thr Pro Pro Tyr Val Tyr Arg Asp Thr Cys Asn Ser Ser Leu 275 280 285 Ala Ser Leu Arg Leu Lys Ala Lys Gln His Ser Ser Phe Gly Tyr Ala 290 295 300 Ser Val Gln Asn Pro Ala Ser Asn Leu Ser Ala Cys Gln Tyr Ala Val 305 310 315 320 Asp Arg Pro Val <![CDATA[<210> 54]]> <![CDATA[<211> 553]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 54]]> Met Gln Ala Arg Tyr Ser Val Ser Ser Pro Asn Ser Leu Gly Val Val 1 5 10 15 Pro Tyr Leu Gly Gly Glu Gln Ser Tyr Tyr Arg Ala Ala Ala Ala Ala 20 25 30 Ala Gly Gly Gly Tyr Thr Ala Met Pro Ala Pro Met Ser Val Tyr Ser 35 40 45 His Pro Ala His Ala Glu Gln Tyr Pro Gly Gly Met Ala Arg Ala Tyr 50 55 60 Gly Pro Tyr Thr Pro Gln Pro Gln Pro Lys Asp Met Val Lys Pro Pro 65 70 75 80 Tyr Ser Tyr Ile Ala Leu Ile Thr Met Ala Ile Gln Asn Ala Pro Asp 85 90 95 Lys Lys Ile Thr Leu Asn Gly Ile Tyr Gln Phe Ile Met Asp Arg Phe 100 105 110 Pro Phe Tyr Arg Asp Asn Lys Gln Gly Trp Gln Asn Ser Ile Arg His 115 120 125 Asn Leu Ser Leu Asn Glu Cys Phe Val Lys Val Pro Arg Asp Asp Lys 130 135 140 Lys Pro Gly Lys Gly Ser Tyr Trp Thr Leu Asp Pro Asp Ser Tyr Asn 145 150 155 160 Met Phe Glu Asn Gly Ser Phe Leu Arg Arg Arg Arg Arg Phe Lys Lys 165 170 175 Lys Asp Ala Val Lys Asp Lys Glu Glu Lys Asp Arg Leu His Leu Lys 180 185 190 Glu Pro Pro Pro Pro Gly Arg Gln Pro Pro Pro Ala Pro Pro Glu Gln 195 200 205 Ala Asp Gly Asn Ala Pro Gly Pro Gln Pro Pro Pro Val Arg Ile Gln 210 215 220 Asp Ile Lys Thr Glu Asn Gly Thr Cys Pro Ser Pro Pro Gln Pro Leu 225 230 235 240 Ser Pro Ala Ala Ala Leu Gly Ser Gly Ser Ala Ala Ala Val Pro Lys 245 250 255 Ile Glu Ser Pro Asp Ser Ser Ser Ser Ser Leu Ser Ser Gly Ser Ser 260 265 270 Pro Pro Gly Ser Leu Pro Ser Ala Arg Pro Leu Ser Leu Asp Gly Ala 275 280 285 Asp Ser Ala Pro Pro Pro Pro Ala Pro Ser Ala Pro Pro Pro His His 290 295 300 Ser Gln Gly Phe Ser Val Asp Asn Ile Met Thr Ser Leu Arg Gly Ser 305 310 315 320 Pro Gln Ser Ala Ala Ala Glu Leu Ser Ser Gly Leu Leu Ala Ser Ala 325 330 335 Ala Ala Ser Ser Arg Ala Gly Ile Ala Pro Pro Leu Ala Leu Gly Ala 340 345 350 Tyr Ser Pro Gly Gln Ser Ser Leu Tyr Ser Ser Pro Cys Ser Gln Thr 355 360 365 Ser Ser Ala Gly Ser Ser Gly Gly Gly Gly Gly Gly Ala Gly Ala Ala 370 375 380 Gly Gly Ala Gly Gly Ala Gly Thr Tyr His Cys Asn Leu Gln Ala Met 385 390 395 400 Ser Leu Tyr Ala Ala Gly Glu Arg Gly Gly His Leu Gln Gly Ala Pro 405 410 415 Gly Gly Ala Gly Gly Ser Ala Val Asp Asp Pro Leu Pro Asp Tyr Ser 420 425 430 Leu Pro Pro Val Thr Ser Ser Ser Ser Ser Ser Leu Ser His Gly Gly 435 440 445 Gly Gly Gly Gly Gly Gly Gly Gly Gln Glu Ala Gly His His Pro Ala 450 455 460 Ala His Gln Gly Arg Leu Thr Ser Trp Tyr Leu Asn Gln Ala Gly Gly 465 470 475 480 Asp Leu Gly His Leu Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly 485 490 495 Tyr Pro Gly Gln Gln Gln Asn Phe His Ser Val Arg Glu Met Phe Glu 500 505 510 Ser Gln Arg Ile Gly Leu Asn Asn Ser Pro Val Asn Gly Asn Ser Ser 515 520 525 Cys Gln Met Ala Phe Pro Ser Ser Gln Ser Leu Tyr Arg Thr Ser Gly 530 535 540 Ala Phe Val Tyr Asp Cys Ser Lys Phe 545 550 <![CDATA[<210> 55]]> <![CDATA[<211> 460]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 55]]> Met His Ser Pro Pro Arg Asp Gln Ala Ala Ile Met Leu Trp Lys Leu 1 5 10 15 Val Glu Asn Val Lys Tyr Glu Asp Ile Tyr Glu Asp Arg His Asp Gly 20 25 30 Val Pro Ser His Ser Ser Arg Leu Ser Gln Leu Gly Ser Val Ser Gln 35 40 45 Gly Pro Tyr Ser Ser Ala Pro Pro Leu Ser His Thr Pro Ser Ser Asp 50 55 60 Phe Gln Pro Pro Tyr Phe Pro Pro Pro Tyr Gln Pro Leu Pro Tyr His 65 70 75 80 Gln Ser Gln Asp Pro Tyr Ser His Val Asn Asp Pro Tyr Ser Leu Asn 85 90 95 Pro Leu His Gln Pro Gln Gln His Pro Trp Gly Gln Arg Gln Arg Gln 100 105 110 Glu Val Gly Ser Glu Ala Gly Ser Leu Leu Pro Gln Pro Arg Ala Ala 115 120 125 Leu Pro Gln Leu Ser Gly Leu Asp Pro Arg Arg Asp Tyr His Ser Val 130 135 140 Arg Arg Pro Asp Val Leu Leu His Ser Ala His His Gly Leu Asp Ala 145 150 155 160 Gly Met Gly Asp Ser Leu Ser Leu His Gly Leu Gly His Pro Gly Met 165 170 175 Glu Asp Val Gln Ser Val Glu Asp Ala Asn Asn Ser Gly Met Asn Leu 180 185 190 Leu Asp Gln Ser Val Ile Lys Lys Val Pro Val Pro Pro Lys Ser Val 195 200 205 Thr Ser Leu Met Met Asn Lys Asp Gly Phe Leu Gly Gly Met Ser Val 210 215 220 Asn Thr Gly Glu Val Phe Cys Ser Val Pro Gly Arg Leu Ser Leu Leu 225 230 235 240 Ser Ser Thr Ser Lys Tyr Lys Val Thr Val Gly Glu Val Gln Arg Arg 245 250 255 Leu Ser Pro Pro Glu Cys Leu Asn Ala Ser Leu Leu Gly Gly Val Leu 260 265 270 Arg Arg Ala Lys Ser Lys Asn Gly Gly Arg Ser Leu Arg Glu Arg Leu 275 280 285 Glu Lys Ile Gly Leu Asn Leu Pro Ala Gly Arg Arg Lys Ala Ala Asn 290 295 300 Val Thr Leu Leu Thr Ser Leu Val Glu Gly Glu Ala Val His Leu Ala 305 310 315 320 Arg Asp Phe Gly Tyr Ile Cys Glu Thr Glu Phe Pro Ala Lys Ala Val 325 330 335 Ser Glu Tyr Leu Asn Arg Gln His Thr Asp Pro Ser Asp Leu His Ser 340 345 350 Arg Lys Asn Met Leu Leu Ala Thr Lys Gln Leu Cys Lys Glu Phe Thr 355 360 365 Asp Leu Leu Ala Gln Asp Arg Thr Pro Ile Gly Asn Ser Arg Pro Ser 370 375 380 Pro Ile Leu Glu Pro Gly Ile Gln Ser Cys Leu Thr His Phe Ser Leu 385 390 395 400 Ile Thr His Gly Phe Gly Ala Pro Ala Ile Cys Ala Ala Leu Thr Ala 405 410 415 Leu Gln Asn Tyr Leu Thr Glu Ala Leu Lys Gly Met Asp Lys Met Phe 420 425 430 Leu Asn Asn Thr Thr Thr Asn Arg His Thr Ser Gly Glu Gly Pro Gly 435 440 445 Ser Lys Thr Gly Asp Lys Glu Glu Lys His Arg Lys 450 455 460 <![CDATA[<210> 56]]> <![CDATA[<211> 406]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 56]]> Met Asp Ile Ala Thr Gly Pro Glu Ser Leu Glu Arg Cys Phe Pro Arg 1 5 10 15 Gly Gln Thr Asp Cys Ala Lys Met Leu Asp Gly Ile Lys Met Glu Glu 20 25 30 His Ala Leu Arg Pro Gly Pro Ala Thr Leu Gly Val Leu Leu Gly Ser 35 40 45 Asp Cys Pro His Pro Ala Val Cys Glu Gly Cys Gln Arg Pro Ile Ser 50 55 60 Asp Arg Phe Leu Met Arg Val Asn Glu Ser Ser Trp His Glu Glu Cys 65 70 75 80 Leu Gln Cys Ala Ala Cys Gln Gln Ala Leu Thr Thr Ser Cys Tyr Phe 85 90 95 Arg Asp Arg Lys Leu Tyr Cys Lys Gln Asp Tyr Gln Gln Leu Phe Ala 100 105 110 Ala Lys Cys Ser Gly Cys Met Glu Lys Ile Ala Pro Thr Glu Phe Val 115 120 125 Met Arg Ala Leu Glu Cys Val Tyr His Leu Gly Cys Phe Cys Cys Cys 130 135 140 Val Cys Glu Arg Gln Leu Arg Lys Gly Asp Glu Phe Val Leu Lys Glu 145 150 155 160 Gly Gln Leu Leu Cys Lys Gly Asp Tyr Glu Lys Glu Lys Asp Leu Leu 165 170 175 Ser Ser Val Ser Pro Asp Glu Ser Asp Ser Val Lys Ser Glu Asp Glu 180 185 190 Asp Gly Asp Met Lys Pro Ala Lys Gly Gln Gly Ser Gln Ser Lys Gly 195 200 205 Ser Gly Asp Asp Gly Lys Asp Pro Arg Arg Pro Lys Arg Pro Arg Thr 210 215 220 Ile Leu Thr Thr Gln Gln Arg Arg Ala Phe Lys Ala Ser Phe Glu Val 225 230 235 240 Ser Ser Lys Pro Cys Arg Lys Val Arg Glu Thr Leu Ala Ala Glu Thr 245 250 255 Gly Leu Ser Val Arg Val Val Gln Val Trp Phe Gln Asn Gln Arg Ala 260 265 270 Lys Met Lys Lys Leu Ala Arg Arg His Gln Gln Gln Gln Glu Gln Gln 275 280 285 Asn Ser Gln Arg Leu Gly Gln Gly Glu Pro Gly Pro Gly Gln Gly Leu 290 295 300 Gly Gln Glu Val Leu Ser Ser Arg Met Glu Gly Met Met Ala Ser Tyr 305 310 315 320 Thr Pro Leu Ala Pro Pro Gln Gln Gln Ile Val Ala Met Glu Gln Ser 325 330 335 Pro Tyr Gly Ser Ser Asp Pro Phe Gln Gln Gly Leu Thr Pro Pro Gln 340 345 350 Met Pro Gly Asn Asp Ser Ile Phe His Asp Ile Asp Ser Asp Thr Ser 355 360 365 Leu Thr Ser Leu Ser Asp Cys Phe Leu Gly Ser Ser Asp Val Gly Ser 370 375 380 Leu Gln Ala Arg Val Gly Asn Pro Ile Asp Arg Leu Tyr Ser Met Gln 385 390 395 400 Ser Ser Tyr Phe Ala Ser 405 <![CDATA[<210> 57]]> <![CDATA[<211> 395]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 57]]> Met Asp Ile Ala Thr Gly Pro Glu Ser Leu Glu Arg Cys Phe Pro Arg 1 5 10 15 Gly Gln Thr Asp Cys Ala Lys Met Leu Asp Gly Ile Lys Met Glu Glu 20 25 30 His Ala Leu Arg Pro Gly Pro Ala Thr Leu Gly Val Leu Leu Gly Ser 35 40 45 Asp Cys Pro His Pro Ala Val Cys Glu Gly Cys Gln Arg Pro Ile Ser 50 55 60 Asp Arg Phe Leu Met Arg Val Asn Glu Ser Ser Trp His Glu Glu Cys 65 70 75 80 Leu Gln Cys Ala Ala Cys Gln Gln Ala Leu Thr Thr Ser Cys Tyr Phe 85 90 95 Arg Asp Arg Lys Leu Tyr Cys Lys Gln Asp Tyr Gln Gln Leu Phe Ala 100 105 110 Ala Lys Cys Ser Gly Cys Met Glu Lys Ile Ala Pro Thr Glu Phe Val 115 120 125 Met Arg Ala Leu Glu Cys Val Tyr His Leu Gly Cys Phe Cys Cys Cys 130 135 140 Val Cys Glu Arg Gln Leu Arg Lys Gly Asp Glu Phe Val Leu Lys Glu 145 150 155 160 Gly Gln Leu Leu Cys Lys Gly Asp Tyr Glu Lys Glu Lys Asp Leu Leu 165 170 175 Ser Ser Val Ser Pro Asp Glu Ser Asp Ser Val Lys Ser Glu Asp Glu 180 185 190 Asp Gly Asp Met Lys Pro Ala Lys Gly Gln Gly Ser Gln Ser Lys Gly 195 200 205 Ser Gly Asp Asp Gly Lys Asp Pro Arg Arg Pro Lys Arg Pro Arg Thr 210 215 220 Ile Leu Thr Thr Gln Gln Arg Arg Ala Phe Lys Ala Ser Phe Glu Val 225 230 235 240 Ser Ser Lys Pro Cys Arg Lys Val Arg Glu Thr Leu Ala Ala Glu Thr 245 250 255 Gly Leu Ser Val Arg Val Val Gln Val Trp Phe Gln Asn Gln Arg Ala 260 265 270 Lys Met Lys Lys Leu Ala Arg Arg His Gln Gln Gln Gln Glu Gln Gln 275 280 285 Asn Ser Gln Arg Leu Gly Gln Glu Val Leu Ser Ser Arg Met Glu Gly 290 295 300 Met Met Ala Ser Tyr Thr Pro Leu Ala Pro Pro Gln Gln Gln Ile Val 305 310 315 320 Ala Met Glu Gln Ser Pro Tyr Gly Ser Ser Asp Pro Phe Gln Gln Gly 325 330 335 Leu Thr Pro Pro Gln Met Pro Gly Asn Asp Ser Ile Phe His Asp Ile 340 345 350 Asp Ser Asp Thr Ser Leu Thr Ser Leu Ser Asp Cys Phe Leu Gly Ser 355 360 365 Ser Asp Val Gly Ser Leu Gln Ala Arg Val Gly Asn Pro Ile Asp Arg 370 375 380 Leu Tyr Ser Met Gln Ser Ser Tyr Phe Ala Ser 385 390 395 <![CDATA[<210> 58]]> <![CDATA[<211> 402]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 58]]> Met Asp Ile Ala Thr Gly Pro Glu Ser Leu Glu Arg Cys Phe Pro Arg 1 5 10 15 Gly Gln Thr Asp Cys Ala Lys Met Leu Asp Gly Ile Lys Met Glu Glu 20 25 30 His Ala Leu Arg Pro Gly Pro Ala Thr Leu Gly Val Leu Leu Gly Ser 35 40 45 Asp Cys Pro His Pro Ala Val Cys Glu Gly Cys Gln Arg Pro Ile Ser 50 55 60 Asp Arg Phe Leu Met Arg Val Asn Glu Ser Ser Trp His Glu Glu Cys 65 70 75 80 Leu Gln Cys Ala Ala Cys Gln Gln Ala Leu Thr Thr Ser Cys Tyr Phe 85 90 95 Arg Asp Arg Lys Leu Tyr Cys Lys Gln Asp Tyr Gln Gln Leu Phe Ala 100 105 110 Ala Lys Cys Ser Gly Cys Met Glu Lys Ile Ala Pro Thr Glu Phe Val 115 120 125 Met Arg Ala Leu Glu Cys Val Tyr His Leu Gly Cys Phe Cys Cys Cys 130 135 140 Val Cys Glu Arg Gln Leu Arg Lys Gly Asp Glu Phe Val Leu Lys Glu 145 150 155 160 Gly Gln Leu Leu Cys Lys Gly Asp Tyr Glu Lys Glu Lys Asp Leu Leu 165 170 175 Ser Ser Val Ser Pro Asp Glu Ser Asp Ser Val Lys Ser Glu Asp Glu 180 185 190 Asp Gly Asp Met Lys Pro Ala Lys Gly Gln Gly Ser Gln Ser Lys Gly 195 200 205 Ser Gly Asp Asp Gly Lys Asp Pro Arg Arg Pro Lys Arg Pro Arg Thr 210 215 220 Ile Leu Thr Thr Gln Gln Arg Arg Ala Phe Lys Ala Ser Phe Glu Val 225 230 235 240 Ser Ser Lys Pro Cys Arg Lys Val Arg Glu Thr Leu Ala Ala Glu Thr 245 250 255 Gly Leu Ser Val Arg Val Val Gln Val Trp Phe Gln Asn Gln Arg Ala 260 265 270 Lys Met Lys Lys Leu Ala Arg Arg His Gln Gln Gln Gln Glu Gln Gln 275 280 285 Asn Ser Gln Arg Leu Gly Gln Glu Val Leu Ser Ser Arg Met Glu Gly 290 295 300 Met Met Ala Ser Tyr Thr Pro Leu Ala Pro Pro Gln Gln Gln Ile Val 305 310 315 320 Ala Met Glu Gln Ser Pro Tyr Gly Ser Ser Asp Pro Phe Gln Gln Gly 325 330 335 Leu Thr Pro Pro Gln Met Pro Gly Asp His Met Asn Pro Tyr Gly Asn 340 345 350 Asp Ser Ile Phe His Asp Ile Asp Ser Asp Thr Ser Leu Thr Ser Leu 355 360 365 Ser Asp Cys Phe Leu Gly Ser Ser Asp Val Gly Ser Leu Gln Ala Arg 370 375 380 Val Gly Asn Pro Ile Asp Arg Leu Tyr Ser Met Gln Ser Ser Tyr Phe 385 390 395 400 Ala Ser <![CDATA[<210> 59]]> <![CDATA[<211> 691]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 59]]> Met Ser Ala Leu Leu Gln Asp Pro Met Ile Ala Gly Gln Val Ser Lys 1 5 10 15 Pro Leu Leu Ser Val Arg Ser Glu Met Asn Ala Glu Leu Arg Gly Glu 20 25 30 Asp Lys Ala Ala Thr Ser Asp Ser Glu Leu Asn Glu Pro Leu Leu Ala 35 40 45 Pro Val Glu Ser Asn Asp Ser Glu Asp Thr Pro Ser Lys Leu Phe Gly 50 55 60 Ala Arg Gly Asn Pro Ala Leu Ser Asp Pro Gly Thr Pro Asp Gln His 65 70 75 80 Gln Ala Ser Gln Thr His Pro Pro Phe Pro Val Gly Pro Gln Pro Leu 85 90 95 Leu Thr Ala Gln Gln Leu Ala Ser Ala Val Ala Gly Val Met Pro Gly 100 105 110 Gly Pro Pro Ala Leu Asn Gln Pro Ile Leu Ile Pro Phe Asn Met Ala 115 120 125 Gly Gln Leu Gly Gly Gln Gln Gly Leu Val Leu Thr Leu Pro Thr Ala 130 135 140 Asn Leu Thr Asn Ile Gln Gly Leu Val Ala Ala Ala Ala Ala Gly Gly 145 150 155 160 Ile Met Thr Leu Pro Leu Gln Asn Leu Gln Ala Thr Ser Ser Leu Asn 165 170 175 Ser Gln Leu Gln Gln Leu Gln Leu Gln Leu Gln Gln Gln Gln Gln Gln 180 185 190 Gln Gln Gln Gln Pro Pro Pro Ser Thr Asn Gln His Pro Gln Pro Ala 195 200 205 Pro Gln Ala Pro Ser Gln Ser Gln Gln Gln Pro Leu Gln Pro Thr Pro 210 215 220 Pro Gln Gln Pro Pro Pro Ala Ser Gln Gln Pro Pro Ala Pro Thr Ser 225 230 235 240 Gln Leu Gln Gln Ala Pro Gln Pro Gln Gln His Gln Pro His Ser His 245 250 255 Ser Gln Asn Gln Asn Gln Pro Ser Pro Thr Gln Gln Ser Ser Ser Pro 260 265 270 Pro Gln Lys Pro Ser Gln Ser Pro Gly His Gly Leu Pro Ser Pro Leu 275 280 285 Thr Pro Pro Asn Pro Leu Gln Leu Val Asn Asn Pro Leu Ala Ser Gln 290 295 300 Ala Ala Ala Ala Ala Ala Ala Met Ser Ser Ile Ala Ser Ser Gln Ala 305 310 315 320 Phe Gly Asn Ala Leu Ser Ser Leu Gln Gly Val Thr Gly Gln Leu Val 325 330 335 Thr Asn Ala Gln Gly Gln Ile Ile Gly Thr Ile Pro Leu Met Pro Asn 340 345 350 Pro Gly Pro Ser Ser Gln Ala Ala Ser Gly Thr Gln Gly Leu Gln Val 355 360 365 Gln Pro Ile Thr Pro Gln Leu Leu Thr Asn Ala Gln Gly Gln Ile Ile 370 375 380 Ala Thr Val Ile Gly Asn Gln Ile Leu Pro Val Ile Asn Thr Gln Gly 385 390 395 400 Ile Thr Leu Ser Pro Ile Lys Pro Gly Gln Gln Leu His Gln Pro Ser 405 410 415 Gln Thr Ser Val Gly Gln Ala Ala Ser Gln Gly Asn Leu Leu His Leu 420 425 430 Ala His Ser Gln Ala Ser Met Ser Gln Ser Pro Val Arg Gln Ala Ser 435 440 445 Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ala Leu Ser Val Gly Gln 450 455 460 Leu Val Ser Asn Pro Gln Thr Ala Ala Gly Glu Val Asp Gly Val Asn 465 470 475 480 Leu Glu Glu Ile Arg Glu Phe Ala Lys Ala Phe Lys Ile Arg Arg Leu 485 490 495 Ser Leu Gly Leu Thr Gln Thr Gln Val Gly Gln Ala Leu Ser Ala Thr 500 505 510 Glu Gly Pro Ala Tyr Ser Gln Ser Ala Ile Cys Arg His Thr Ile Leu 515 520 525 Arg Ser His Phe Phe Leu Pro Gln Glu Ala Gln Glu Asn Thr Ile Ala 530 535 540 Ser Ser Leu Thr Ala Lys Leu Asn Pro Gly Leu Leu Tyr Pro Ala Arg 545 550 555 560 Phe Glu Lys Leu Asp Ile Thr Pro Lys Ser Ala Gln Lys Ile Lys Pro 565 570 575 Val Leu Glu Arg Trp Met Ala Glu Ala Glu Ala Arg His Arg Ala Gly 580 585 590 Met Gln Asn Leu Thr Glu Phe Ile Gly Ser Glu Pro Ser Lys Lys Arg 595 600 605 Lys Arg Arg Thr Ser Phe Thr Pro Gln Ala Leu Glu Ile Leu Asn Ala 610 615 620 His Phe Glu Lys Asn Thr His Pro Ser Gly Gln Glu Met Thr Glu Ile 625 630 635 640 Ala Glu Lys Leu Asn Tyr Asp Arg Glu Val Val Arg Val Trp Phe Cys 645 650 655 Asn Lys Arg Gln Ala Leu Lys Asn Thr Ile Lys Arg Leu Lys Gln His 660 665 670 Glu Pro Ala Thr Ala Val Pro Leu Glu Pro Leu Thr Asp Ser Leu Glu 675 680 685 Glu Asn Ser 690 <![CDATA[<210> 60]]> <![CDATA[<211> 655]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 60]]> Met Ser Ala Leu Leu Gln Asp Pro Met Ile Ala Gly Gln Val Ser Lys 1 5 10 15 Pro Leu Leu Ser Val Arg Ser Glu Met Asn Ala Glu Leu Arg Gly Glu 20 25 30 Asp Lys Ala Ala Thr Ser Asp Ser Glu Leu Asn Glu Pro Leu Leu Ala 35 40 45 Pro Val Glu Ser Asn Asp Ser Glu Asp Thr Pro Ser Lys Leu Phe Gly 50 55 60 Ala Arg Gly Asn Pro Ala Leu Ser Asp Pro Gly Thr Pro Asp Gln His 65 70 75 80 Gln Ala Ser Gln Thr His Pro Pro Phe Pro Val Gly Pro Gln Pro Leu 85 90 95 Leu Thr Ala Gln Gln Leu Ala Ser Ala Val Ala Gly Val Met Pro Gly 100 105 110 Gly Pro Pro Ala Leu Asn Gln Pro Ile Leu Ile Pro Phe Asn Met Ala 115 120 125 Gly Gln Leu Gly Gly Gln Gln Gly Leu Val Leu Thr Leu Pro Thr Ala 130 135 140 Asn Leu Thr Asn Ile Gln Gly Leu Val Ala Ala Ala Ala Ala Gly Gly 145 150 155 160 Ile Met Thr Leu Pro Leu Gln Asn Leu Gln Ala Thr Ser Ser Leu Asn 165 170 175 Ser Gln Leu Gln Gln Leu Gln Leu Gln Leu Gln Gln Gln Gln Gln Gln 180 185 190 Gln Gln Gln Gln Pro Pro Pro Ser Thr Asn Gln His Pro Gln Pro Ala 195 200 205 Pro Gln Ala Pro Ser Gln Ser Gln Gln Gln Pro Leu Gln Pro Thr Pro 210 215 220 Pro Gln Gln Pro Pro Pro Ala Ser Gln Gln Pro Pro Ala Pro Thr Ser 225 230 235 240 Gln Leu Gln Gln Ala Pro Gln Pro Gln Gln His Gln Pro His Ser His 245 250 255 Ser Gln Asn Gln Asn Gln Pro Ser Pro Thr Gln Gln Ser Ser Ser Pro 260 265 270 Pro Gln Lys Pro Ser Gln Ser Pro Gly His Gly Leu Pro Ser Pro Leu 275 280 285 Thr Pro Pro Asn Pro Leu Gln Leu Val Asn Asn Pro Leu Ala Ser Gln 290 295 300 Ala Ala Ala Ala Ala Ala Ala Met Ser Ser Ile Ala Ser Ser Gln Ala 305 310 315 320 Phe Gly Asn Ala Leu Ser Ser Leu Gln Gly Val Thr Gly Gln Leu Val 325 330 335 Thr Asn Ala Gln Gly Gln Ile Ile Gly Thr Ile Pro Leu Met Pro Asn 340 345 350 Pro Gly Pro Ser Ser Gln Ala Ala Ser Gly Thr Gln Gly Leu Gln Val 355 360 365 Gln Pro Ile Thr Pro Gln Leu Leu Thr Asn Ala Gln Gly Gln Ile Ile 370 375 380 Ala Thr Val Ile Gly Asn Gln Ile Leu Pro Val Ile Asn Thr Gln Gly 385 390 395 400 Ile Thr Leu Ser Pro Ile Lys Pro Gly Gln Gln Leu His Gln Pro Ser 405 410 415 Gln Thr Ser Val Gly Gln Ala Ala Ser Gln Gly Asn Leu Leu His Leu 420 425 430 Ala His Ser Gln Ala Ser Met Ser Gln Ser Pro Val Arg Gln Ala Ser 435 440 445 Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ala Leu Ser Val Gly Gln 450 455 460 Leu Val Ser Asn Pro Gln Thr Ala Ala Gly Glu Val Asp Gly Val Asn 465 470 475 480 Leu Glu Glu Ile Arg Glu Phe Ala Lys Ala Phe Lys Ile Arg Arg Leu 485 490 495 Ser Leu Gly Leu Thr Gln Thr Gln Val Gly Gln Ala Leu Ser Ala Thr 500 505 510 Glu Gly Pro Ala Tyr Ser Gln Ser Ala Ile Cys Arg Phe Glu Lys Leu 515 520 525 Asp Ile Thr Pro Lys Ser Ala Gln Lys Ile Lys Pro Val Leu Glu Arg 530 535 540 Trp Met Ala Glu Ala Glu Ala Arg His Arg Ala Gly Met Gln Asn Leu 545 550 555 560 Thr Glu Phe Ile Gly Ser Glu Pro Ser Lys Lys Arg Lys Arg Arg Thr 565 570 575 Ser Phe Thr Pro Gln Ala Leu Glu Ile Leu Asn Ala His Phe Glu Lys 580 585 590 Asn Thr His Pro Ser Gly Gln Glu Met Thr Glu Ile Ala Glu Lys Leu 595 600 605 Asn Tyr Asp Arg Glu Val Val Arg Val Trp Phe Cys Asn Lys Arg Gln 610 615 620 Ala Leu Lys Asn Thr Ile Lys Arg Leu Lys Gln His Glu Pro Ala Thr 625 630 635 640 Ala Val Pro Leu Glu Pro Leu Thr Asp Ser Leu Glu Glu Asn Ser 645 650 655 <![CDATA[<210> 61]]> <![CDATA[<211> 351]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 61]]> Met Thr Glu Met Ser Phe Leu Ser Ser Glu Val Leu Val Gly Asp Leu 1 5 10 15 Met Ser Pro Phe Asp Gln Ser Gly Leu Gly Ala Glu Glu Ser Leu Gly 20 25 30 Leu Leu Asp Asp Tyr Leu Glu Val Ala Lys His Phe Lys Pro His Gly 35 40 45 Phe Ser Ser Asp Lys Ala Lys Ala Gly Ser Ser Glu Trp Leu Ala Val 50 55 60 Asp Gly Leu Val Ser Pro Ser Asn Asn Ser Lys Glu Asp Ala Phe Ser 65 70 75 80 Gly Thr Asp Trp Met Leu Glu Lys Met Asp Leu Lys Glu Phe Asp Leu 85 90 95 Asp Ala Leu Leu Gly Ile Asp Asp Leu Glu Thr Met Pro Asp Asp Leu 100 105 110 Leu Thr Thr Leu Asp Asp Thr Cys Asp Leu Phe Ala Pro Leu Val Gln 115 120 125 Glu Thr Asn Lys Gln Pro Pro Gln Thr Val Asn Pro Ile Gly His Leu 130 135 140 Pro Glu Ser Leu Thr Lys Pro Asp Gln Val Ala Pro Phe Thr Phe Leu 145 150 155 160 Gln Pro Leu Pro Leu Ser Pro Gly Val Leu Ser Ser Thr Pro Asp His 165 170 175 Ser Phe Ser Leu Glu Leu Gly Ser Glu Val Asp Ile Thr Glu Gly Asp 180 185 190 Arg Lys Pro Asp Tyr Thr Ala Tyr Val Ala Met Ile Pro Gln Cys Ile 195 200 205 Lys Glu Glu Asp Thr Pro Ser Asp Asn Asp Ser Gly Ile Cys Met Ser 210 215 220 Pro Glu Ser Tyr Leu Gly Ser Pro Gln His Ser Pro Ser Thr Arg Gly 225 230 235 240 Ser Pro Asn Arg Ser Leu Pro Ser Pro Gly Val Leu Cys Gly Ser Ala 245 250 255 Arg Pro Lys Pro Tyr Asp Pro Pro Gly Glu Lys Met Val Ala Ala Lys 260 265 270 Val Lys Gly Glu Lys Leu Asp Lys Lys Leu Lys Lys Met Glu Gln Asn 275 280 285 Lys Thr Ala Ala Thr Arg Tyr Arg Gln Lys Lys Arg Ala Glu Gln Glu 290 295 300 Ala Leu Thr Gly Glu Cys Lys Glu Leu Glu Lys Lys Asn Glu Ala Leu 305 310 315 320 Lys Glu Arg Ala Asp Ser Leu Ala Lys Glu Ile Gln Tyr Leu Lys Asp 325 330 335 Leu Ile Glu Glu Val Arg Lys Ala Arg Gly Lys Lys Arg Val Pro 340 345 350 <![CDATA[<210> 62]]> <![CDATA[<211> 823]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 62]]> Met Ala Ala Ser Glu Ala Ala Ala Ala Ala Gly Ser Ala Ala Leu Ala 1 5 10 15 Ala Gly Ala Arg Ala Val Pro Ala Ala Thr Thr Gly Ala Ala Ala Ala 20 25 30 Ala Ser Gly Pro Trp Val Pro Pro Gly Pro Arg Leu Arg Gly Ser Arg 35 40 45 Pro Arg Pro Ala Gly Ala Thr Gln Gln Pro Ala Val Pro Ala Pro Pro 50 55 60 Ala Gly Glu Leu Ile Gln Pro Ser Val Ser Glu Leu Ser Arg Ala Val 65 70 75 80 Arg Thr Asn Ile Leu Cys Thr Val Arg Gly Cys Gly Lys Ile Leu Pro 85 90 95 Asn Ser Pro Ala Leu Asn Met His Leu Val Lys Ser His Arg Leu Gln 100 105 110 Asp Gly Ile Val Asn Pro Thr Ile Arg Lys Asp Leu Lys Thr Gly Pro 115 120 125 Lys Phe Tyr Cys Cys Pro Ile Glu Gly Cys Pro Arg Gly Pro Glu Arg 130 135 140 Pro Phe Ser Gln Phe Ser Leu Val Lys Gln His Phe Met Lys Met His 145 150 155 160 Ala Glu Lys Lys His Lys Cys Ser Lys Cys Ser Asn Ser Tyr Gly Thr 165 170 175 Glu Trp Asp Leu Lys Arg His Ala Glu Asp Cys Gly Lys Thr Phe Arg 180 185 190 Cys Thr Cys Gly Cys Pro Tyr Ala Ser Arg Thr Ala Leu Gln Ser His 195 200 205 Ile Tyr Arg Thr Gly His Glu Ile Pro Ala Glu His Arg Asp Pro Pro 210 215 220 Ser Lys Lys Arg Lys Met Glu Asn Cys Ala Gln Asn Gln Lys Leu Ser 225 230 235 240 Asn Lys Thr Ile Glu Ser Leu Asn Asn Gln Pro Ile Pro Arg Pro Asp 245 250 255 Thr Gln Glu Leu Glu Ala Ser Glu Ile Lys Leu Glu Pro Ser Phe Glu 260 265 270 Asp Ser Cys Gly Ser Asn Thr Asp Lys Gln Thr Leu Thr Thr Pro Pro 275 280 285 Arg Tyr Pro Gln Lys Leu Leu Leu Pro Lys Pro Lys Val Ala Leu Val 290 295 300 Lys Leu Pro Val Met Gln Phe Ser Val Met Pro Val Phe Val Pro Thr 305 310 315 320 Ala Asp Ser Ser Ala Gln Pro Val Val Leu Gly Val Asp Gln Gly Ser 325 330 335 Ala Thr Gly Ala Val His Leu Met Pro Leu Ser Val Gly Thr Leu Ile 340 345 350 Leu Gly Leu Asp Ser Glu Ala Cys Ser Leu Lys Glu Ser Leu Pro Leu 355 360 365 Phe Lys Ile Ala Asn Pro Ile Ala Gly Glu Pro Ile Ser Thr Gly Val 370 375 380 Gln Val Asn Phe Gly Lys Ser Pro Ser Asn Pro Leu Gln Glu Leu Gly 385 390 395 400 Asn Thr Cys Gln Lys Asn Ser Ile Ser Ser Ile Asn Val Gln Thr Asp 405 410 415 Leu Ser Tyr Ala Ser Gln Asn Phe Ile Pro Ser Ala Gln Trp Ala Thr 420 425 430 Ala Asp Ser Ser Val Ser Ser Cys Ser Gln Thr Asp Leu Ser Phe Asp 435 440 445 Ser Gln Val Ser Leu Pro Ile Ser Val His Thr Gln Thr Phe Leu Pro 450 455 460 Ser Ser Lys Val Thr Ser Ser Ile Ala Ala Gln Thr Asp Ala Phe Met 465 470 475 480 Asp Thr Cys Phe Gln Ser Gly Gly Val Ser Arg Glu Thr Gln Thr Ser 485 490 495 Gly Ile Glu Ser Pro Thr Asp Asp His Val Gln Met Asp Gln Ala Gly 500 505 510 Met Cys Gly Asp Ile Phe Glu Ser Val His Ser Ser Tyr Asn Val Ala 515 520 525 Thr Gly Asn Ile Ile Ser Asn Ser Leu Val Ala Glu Thr Val Thr His 530 535 540 Ser Leu Leu Pro Gln Asn Glu Pro Lys Thr Leu Asn Gln Asp Ile Glu 545 550 555 560 Lys Ser Ala Pro Ile Ile Asn Phe Ser Ala Gln Asn Ser Met Leu Pro 565 570 575 Ser Gln Asn Met Thr Asp Asn Gln Thr Gln Thr Ile Asp Leu Leu Ser 580 585 590 Asp Leu Glu Asn Ile Leu Ser Ser Asn Leu Pro Ala Gln Thr Leu Asp 595 600 605 His Arg Ser Leu Leu Ser Asp Thr Asn Pro Gly Pro Asp Thr Gln Leu 610 615 620 Pro Ser Gly Pro Ala Gln Asn Pro Gly Ile Asp Phe Asp Ile Glu Glu 625 630 635 640 Phe Phe Ser Ala Ser Asn Ile Gln Thr Gln Thr Glu Glu Ser Glu Leu 645 650 655 Ser Thr Met Thr Thr Glu Pro Val Leu Glu Ser Leu Asp Ile Glu Thr 660 665 670 Gln Thr Asp Phe Leu Leu Ala Asp Thr Ser Ala Gln Ser Tyr Gly Cys 675 680 685 Arg Gly Asn Ser Asn Phe Leu Gly Leu Glu Met Phe Asp Thr Gln Thr 690 695 700 Gln Thr Asp Leu Asn Phe Phe Leu Asp Ser Ser Pro His Leu Pro Leu 705 710 715 720 Gly Ser Ile Leu Lys His Ser Ser Phe Ser Val Ser Thr Asp Ser Ser 725 730 735 Asp Thr Glu Thr Gln Thr Glu Gly Val Ser Thr Ala Lys Asn Ile Pro 740 745 750 Ala Leu Glu Ser Lys Val Gln Leu Asn Ser Thr Glu Thr Gln Thr Met 755 760 765 Ser Ser Gly Phe Glu Thr Leu Gly Ser Leu Phe Phe Thr Ser Asn Glu 770 775 780 Thr Gln Thr Ala Met Asp Asp Phe Leu Leu Ala Asp Leu Ala Trp Asn 785 790 795 800 Thr Met Glu Ser Gln Phe Ser Ser Val Glu Thr Gln Thr Ser Ala Glu 805 810 815 Pro His Thr Val Ser Asn Phe 820 <![CDATA[<210> 63]]> <![CDATA[<211> 412]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 63]]> Met Glu Arg Ile Pro Ser Ala Gln Pro Pro Pro Ala Cys Leu Pro Lys 1 5 10 15 Ala Pro Gly Leu Glu His Gly Asp Leu Pro Gly Met Tyr Pro Ala His 20 25 30 Met Tyr Gln Val Tyr Lys Ser Arg Arg Gly Ile Lys Arg Ser Glu Asp 35 40 45 Ser Lys Glu Thr Tyr Lys Leu Pro His Arg Leu Ile Glu Lys Lys Arg 50 55 60 Arg Asp Arg Ile Asn Glu Cys Ile Ala Gln Leu Lys Asp Leu Leu Pro 65 70 75 80 Glu His Leu Lys Leu Thr Thr Leu Gly His Leu Glu Lys Ala Val Val 85 90 95 Leu Glu Leu Thr Leu Lys His Val Lys Ala Leu Thr Asn Leu Ile Asp 100 105 110 Gln Gln Gln Gln Lys Ile Ile Ala Leu Gln Ser Gly Leu Gln Ala Gly 115 120 125 Glu Leu Ser Gly Arg Asn Val Glu Thr Gly Gln Glu Met Phe Cys Ser 130 135 140 Gly Phe Gln Thr Cys Ala Arg Glu Val Leu Gln Tyr Leu Ala Lys His 145 150 155 160 Glu Asn Thr Arg Asp Leu Lys Ser Ser Gln Leu Val Thr His Leu His 165 170 175 Arg Val Val Ser Glu Leu Leu Gln Gly Gly Thr Ser Arg Lys Pro Ser 180 185 190 Asp Pro Ala Pro Lys Val Met Asp Phe Lys Glu Lys Pro Ser Ser Pro 195 200 205 Ala Lys Gly Ser Glu Gly Pro Gly Lys Asn Cys Val Pro Val Ile Gln 210 215 220 Arg Thr Phe Ala His Ser Ser Gly Glu Gln Ser Gly Ser Asp Thr Asp 225 230 235 240 Thr Asp Ser Gly Tyr Gly Gly Glu Ser Glu Lys Gly Asp Leu Arg Ser 245 250 255 Glu Gln Pro Cys Phe Lys Ser Asp His Gly Arg Arg Phe Thr Met Gly 260 265 270 Glu Arg Ile Gly Ala Ile Lys Gln Glu Ser Glu Glu Pro Pro Thr Lys 275 280 285 Lys Asn Arg Met Gln Leu Ser Asp Asp Glu Gly His Phe Thr Ser Ser 290 295 300 Asp Leu Ile Ser Ser Pro Phe Leu Gly Pro His Pro His Gln Pro Pro 305 310 315 320 Phe Cys Leu Pro Phe Tyr Leu Ile Pro Pro Ser Ala Thr Ala Tyr Leu 325 330 335 Pro Met Leu Glu Lys Cys Trp Tyr Pro Thr Ser Val Pro Val Leu Tyr 340 345 350 Pro Gly Leu Asn Ala Ser Ala Ala Ala Leu Ser Ser Phe Met Asn Pro 355 360 365 Asp Lys Ile Ser Ala Pro Leu Leu Met Pro Gln Arg Leu Pro Ser Pro 370 375 380 Leu Pro Ala His Pro Ser Val Asp Ser Ser Val Leu Leu Gln Ala Leu 385 390 395 400 Lys Pro Ile Pro Pro Leu Asn Leu Glu Thr Lys Asp 405 410 <![CDATA[<210> 64]]> <![CDATA[<211> 269]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 64]]> Met Ser Ala Ala Leu Phe Ser Leu Asp Gly Pro Ala Arg Gly Ala Pro 1 5 10 15 Trp Pro Ala Glu Pro Ala Pro Phe Tyr Glu Pro Gly Arg Ala Gly Lys 20 25 30 Pro Gly Arg Gly Ala Glu Pro Gly Ala Leu Gly Glu Pro Gly Ala Ala 35 40 45 Ala Pro Ala Met Tyr Asp Asp Glu Ser Ala Ile Asp Phe Ser Ala Tyr 50 55 60 Ile Asp Ser Met Ala Ala Val Pro Thr Leu Glu Leu Cys His Asp Glu 65 70 75 80 Leu Phe Ala Asp Leu Phe Asn Ser Asn His Lys Ala Gly Gly Ala Gly 85 90 95 Pro Leu Glu Leu Leu Pro Gly Gly Pro Ala Arg Pro Leu Gly Pro Gly 100 105 110 Pro Ala Ala Pro Arg Leu Leu Lys Arg Glu Pro Asp Trp Gly Asp Gly 115 120 125 Asp Ala Pro Gly Ser Leu Leu Pro Ala Gln Val Ala Ala Cys Ala Gln 130 135 140 Thr Val Val Ser Leu Ala Ala Ala Gly Gln Pro Thr Pro Pro Thr Ser 145 150 155 160 Pro Glu Pro Pro Arg Ser Ser Pro Arg Gln Thr Pro Ala Pro Gly Pro 165 170 175 Ala Arg Glu Lys Ser Ala Gly Lys Arg Gly Pro Asp Arg Gly Ser Pro 180 185 190 Glu Tyr Arg Gln Arg Arg Glu Arg Asn Asn Ile Ala Val Arg Lys Ser 195 200 205 Arg Asp Lys Ala Lys Arg Arg Asn Gln Glu Met Gln Gln Lys Leu Val 210 215 220 Glu Leu Ser Ala Glu Asn Glu Lys Leu His Gln Arg Val Glu Gln Leu 225 230 235 240 Thr Arg Asp Leu Ala Gly Leu Arg Gln Phe Phe Lys Gln Leu Pro Ser 245 250 255 Pro Pro Phe Leu Pro Ala Ala Gly Thr Ala Asp Cys Arg 260 265 <![CDATA[<210> 65]]> <![CDATA[<211> 589]]> <![CDATA[<21]]>2> PRT]]> <br/><![CDATA[<213> 智人]]> <br/> <br/><![CDATA[<400> 65]]> <br/> <br/><![CDATA[Met Thr Gly Leu Leu Lys Arg Lys Phe Asp Gln Leu Asp Glu Asp Asn 1 5 10 15 Ser Ser Val Ser Ser Ser Ser Ser Ser Ser Gly Cys Gln Ser Arg Ser 20 25 30 Cys Ser Pro Ser Ser Ser Val Ser Arg Ala Trp Asp Ser Glu Glu Glu 35 40 45 Gly Pro Trp Asp Gln Met Pro Leu Pro Asp Arg Asp Phe Cys Gly Pro 50 55 60 Arg Ser Phe Thr Pro Leu Ser Ile Leu Lys Arg Ala Arg Arg Glu Arg 65 70 75 80 Pro Gly Arg Val Ala Phe Asp Gly Ile Thr Val Phe Tyr Phe Pro Arg 85 90 95 Cys Gln Gly Phe Thr Ser Val Pro Ser Arg Gly Gly Cys Thr Leu Gly 100 105 110 Met Ala Leu Arg His Ser Ala Cys Arg Arg Phe Ser Leu Ala Glu Phe 115 120 125 Ala Gln Glu Gln Ala Arg Ala Arg His Glu Lys Leu Arg Gln Arg Leu 130 135 140 Lys Glu Glu Lys Leu Glu Met Leu Gln Trp Lys Leu Ser Ala Ala Gly 145 150 155 160 Val Pro Gln Ala Glu Ala Gly Leu Pro Pro Val Val Asp Ala Ile Asp 165 170 175 Asp Ala Ser Val Glu Glu Asp Leu Ala Val Ala Val Ala Gly Gly Arg 180 185 190 Leu Glu Glu Val Ser Phe Leu Gln Pro Tyr Pro Ala Arg Arg Arg Arg 195 200 205 Ala Leu Leu Arg Ala Ser Gly Val Arg Arg Ile Asp Arg Glu Glu Lys 210 215 220 Arg Glu Leu Gln Ala Leu Arg Gln Ser Arg Glu Asp Cys Gly Cys His 225 230 235 240 Cys Asp Arg Ile Cys Asp Pro Glu Thr Cys Ser Cys Ser Leu Ala Gly 245 250 255 Ile Lys Cys Gln Met Asp His Thr Ala Phe Pro Cys Gly Cys Cys Arg 260 265 270 Glu Gly Cys Glu Asn Pro Met Gly Arg Val Glu Phe Asn Gln Ala Arg 275 280 285 Val Gln Thr His Phe Ile His Thr Leu Thr Arg Leu Gln Leu Glu Gln 290 295 300 Glu Ala Glu Ser Phe Arg Glu Leu Glu Ala Pro Ala Gln Gly Ser Pro 305 310 315 320 Pro Ser Pro Gly Glu Glu Ala Leu Val Pro Thr Phe Pro Leu Ala Lys 325 330 335 Pro Pro Met Asn Asn Glu Leu Gly Asp Asn Ser Cys Ser Ser Asp Met 340 345 350 Thr Asp Ser Ser Thr Ala Ser Ser Ser Ala Ser Gly Thr Ser Glu Ala 355 360 365 Pro Asp Cys Pro Thr His Pro Gly Leu Pro Gly Pro Gly Phe Gln Pro 370 375 380 Gly Val Asp Asp Asp Ser Leu Ala Arg Ile Leu Ser Phe Ser Asp Ser 385 390 395 400 Asp Phe Gly Gly Glu Glu Glu Glu Glu Glu Glu Gly Ser Val Gly Asn 405 410 415 Leu Asp Asn Leu Ser Cys Phe His Pro Ala Asp Ile Phe Gly Thr Ser 420 425 430 Asp Pro Gly Gly Leu Ala Ser Trp Thr His Ser Tyr Ser Gly Cys Ser 435 440 445 Phe Thr Ser Gly Val Leu Asp Glu Asn Ala Asn Leu Asp Ala Ser Cys 450 455 460 Phe Leu Asn Gly Gly Leu Glu Gly Ser Arg Glu Gly Ser Leu Pro Gly 465 470 475 480 Thr Ser Val Pro Pro Ser Met Asp Ala Gly Arg Ser Ser Ser Val Asp 485 490 495 Leu Ser Leu Ser Ser Cys Asp Ser Phe Glu Leu Leu Gln Ala Leu Pro 500 505 510 Asp Tyr Ser Leu Gly Pro His Tyr Thr Ser Gln Lys Val Ser Asp Ser 515 520 525 Leu Asp Asn Ile Glu Ala Pro His Phe Pro Leu Pro Gly Leu Ser Pro 530 535 540 Pro Gly Asp Ala Ser Ser Cys Phe Leu Glu Ser Leu Met Gly Phe Ser 545 550 555 560 Glu Pro Ala Ala Glu Ala Leu Asp Pro Phe Ile Asp Ser Gln Phe Glu 565 570 575 Asp Thr Val Pro Ala Ser Leu Met Glu Pro Val Pro Val 580 585 <![CDATA[<210> 66]]> <![CDATA[<211> 205]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 66]]> Met Pro Ser Lys Lys Lys Lys Tyr Asn Ala Arg Phe Pro Pro Ala Arg 1 5 10 15 Ile Lys Lys Ile Met Gln Thr Asp Glu Glu Ile Gly Lys Val Ala Ala 20 25 30 Ala Val Pro Val Ile Ile Ser Arg Ala Leu Glu Leu Phe Leu Glu Ser 35 40 45 Leu Leu Lys Lys Ala Cys Gln Val Thr Gln Ser Arg Asn Ala Lys Thr 50 55 60 Met Thr Thr Ser His Leu Lys Gln Cys Ile Glu Leu Glu Gln Gln Phe 65 70 75 80 Asp Phe Leu Lys Asp Leu Val Ala Ser Val Pro Asp Met Gln Gly Asp 85 90 95 Gly Glu Asp Asn His Met Asp Gly Asp Lys Gly Ala Arg Arg Gly Arg 100 105 110 Lys Pro Gly Ser Gly Gly Arg Lys Asn Gly Gly Met Gly Thr Lys Ser 115 120 125 Lys Asp Lys Lys Leu Ser Gly Thr Asp Ser Glu Gln Glu Asp Glu Ser 130 135 140 Glu Asp Thr Asp Thr Asp Gly Glu Glu Glu Thr Ser Gln Pro Pro Pro 145 150 155 160 Gln Ala Ser His Pro Ser Ala His Phe Gln Ser Pro Pro Thr Pro Phe 165 170 175 Leu Pro Phe Ala Ser Thr Leu Pro Leu Pro Pro Ala Pro Pro Gly Pro 180 185 190 Ser Ala Pro Asp Glu Glu Asp Glu Glu Asp Tyr Asp Ser 195 200 205 <![CDATA[<210> 67]]> <![CDATA[<211> 543]]> <![CDATA[<212> PR]]>T <![CDATA[<213> 智人]]> <![CDATA[<400> 67]]> Met Ala Ala Ala Lys Ala Glu Met Gln Leu Met Ser Pro Leu Gln Ile 1 5 10 15 Ser Asp Pro Phe Gly Ser Phe Pro His Ser Pro Thr Met Asp Asn Tyr 20 25 30 Pro Lys Leu Glu Glu Met Met Leu Leu Ser Asn Gly Ala Pro Gln Phe 35 40 45 Leu Gly Ala Ala Gly Ala Pro Glu Gly Ser Gly Ser Asn Ser Ser Ser 50 55 60 Ser Ser Ser Gly Gly Gly Gly Gly Gly Gly Gly Gly Ser Asn Ser Ser 65 70 75 80 Ser Ser Ser Ser Thr Phe Asn Pro Gln Ala Asp Thr Gly Glu Gln Pro 85 90 95 Tyr Glu His Leu Thr Ala Glu Ser Phe Pro Asp Ile Ser Leu Asn Asn 100 105 110 Glu Lys Val Leu Val Glu Thr Ser Tyr Pro Ser Gln Thr Thr Arg Leu 115 120 125 Pro Pro Ile Thr Tyr Thr Gly Arg Phe Ser Leu Glu Pro Ala Pro Asn 130 135 140 Ser Gly Asn Thr Leu Trp Pro Glu Pro Leu Phe Ser Leu Val Ser Gly 145 150 155 160 Leu Val Ser Met Thr Asn Pro Pro Ala Ser Ser Ser Ser Ala Pro Ser 165 170 175 Pro Ala Ala Ser Ser Ala Ser Ala Ser Gln Ser Pro Pro Leu Ser Cys 180 185 190 Ala Val Pro Ser Asn Asp Ser Ser Pro Ile Tyr Ser Ala Ala Pro Thr 195 200 205 Phe Pro Thr Pro Asn Thr Asp Ile Phe Pro Glu Pro Gln Ser Gln Ala 210 215 220 Phe Pro Gly Ser Ala Gly Thr Ala Leu Gln Tyr Pro Pro Pro Ala Tyr 225 230 235 240 Pro Ala Ala Lys Gly Gly Phe Gln Val Pro Met Ile Pro Asp Tyr Leu 245 250 255 Phe Pro Gln Gln Gln Gly Asp Leu Gly Leu Gly Thr Pro Asp Gln Lys 260 265 270 Pro Phe Gln Gly Leu Glu Ser Arg Thr Gln Gln Pro Ser Leu Thr Pro 275 280 285 Leu Ser Thr Ile Lys Ala Phe Ala Thr Gln Ser Gly Ser Gln Asp Leu 290 295 300 Lys Ala Leu Asn Thr Ser Tyr Gln Ser Gln Leu Ile Lys Pro Ser Arg 305 310 315 320 Met Arg Lys Tyr Pro Asn Arg Pro Ser Lys Thr Pro Pro His Glu Arg 325 330 335 Pro Tyr Ala Cys Pro Val Glu Ser Cys Asp Arg Arg Phe Ser Arg Ser 340 345 350 Asp Glu Leu Thr Arg His Ile Arg Ile His Thr Gly Gln Lys Pro Phe 355 360 365 Gln Cys Arg Ile Cys Met Arg Asn Phe Ser Arg Ser Asp His Leu Thr 370 375 380 Thr His Ile Arg Thr His Thr Gly Glu Lys Pro Phe Ala Cys Asp Ile 385 390 395 400 Cys Gly Arg Lys Phe Ala Arg Ser Asp Glu Arg Lys Arg His Thr Lys 405 410 415 Ile His Leu Arg Gln Lys Asp Lys Lys Ala Asp Lys Ser Val Val Ala 420 425 430 Ser Ser Ala Thr Ser Ser Leu Ser Ser Tyr Pro Ser Pro Val Ala Thr 435 440 445 Ser Tyr Pro Ser Pro Val Thr Thr Ser Tyr Pro Ser Pro Ala Thr Thr 450 455 460 Ser Tyr Pro Ser Pro Val Pro Thr Ser Phe Ser Ser Pro Gly Ser Ser 465 470 475 480 Thr Tyr Pro Ser Pro Val His Ser Gly Phe Pro Ser Pro Ser Val Ala 485 490 495 Thr Thr Tyr Ser Ser Val Pro Pro Ala Phe Pro Ala Gln Val Ser Ser 500 505 510 Phe Pro Ser Ser Ala Val Thr Asn Ser Phe Ser Ala Ser Thr Gly Leu 515 520 525 Ser Asp Met Thr Ala Thr Phe Ser Pro Arg Thr Ile Glu Ile Cys 530 535 540 <![CDATA[<210> 68]]> <![CDATA[<211> 581]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 68]]> Met Thr Ser Ala Val Val Asp Ser Gly Gly Thr Ile Leu Glu Leu Ser 1 5 10 15 Ser Asn Gly Val Glu Asn Gln Glu Glu Ser Glu Lys Val Ser Glu Tyr 20 25 30 Pro Ala Val Ile Val Glu Pro Val Pro Ser Ala Arg Leu Glu Gln Gly 35 40 45 Tyr Ala Ala Gln Val Leu Val Tyr Asp Asp Glu Thr Tyr Met Met Gln 50 55 60 Asp Val Ala Glu Glu Gln Glu Val Glu Thr Glu Asn Val Glu Thr Val 65 70 75 80 Glu Ala Ser Val His Ser Ser Asn Ala His Cys Thr Asp Lys Thr Ile 85 90 95 Glu Ala Ala Glu Ala Leu Leu His Met Glu Ser Pro Thr Cys Leu Arg 100 105 110 Asp Ser Arg Ser Pro Glu Phe Ile His Ala Ala Met Arg Pro Asp Val 115 120 125 Ile Thr Glu Thr Val Val Glu Val Ser Thr Glu Glu Ser Glu Pro Met 130 135 140 Asp Thr Ser Pro Ile Pro Thr Ser Pro Asp Ser His Glu Pro Met Lys 145 150 155 160 Lys Lys Lys Val Gly Arg Lys Pro Lys Thr Gln Gln Ser Pro Ile Ser 165 170 175 Asn Gly Ser Pro Glu Leu Gly Ile Lys Lys Lys Pro Arg Glu Gly Lys 180 185 190 Gly Asn Thr Thr Tyr Leu Trp Glu Phe Leu Leu Asp Leu Leu Gln Asp 195 200 205 Lys Asn Thr Cys Pro Arg Tyr Ile Lys Trp Thr Gln Arg Glu Lys Gly 210 215 220 Ile Phe Lys Leu Val Asp Ser Lys Ala Val Ser Lys Leu Trp Gly Lys 225 230 235 240 His Lys Asn Lys Pro Asp Met Asn Tyr Glu Thr Met Gly Arg Ala Leu 245 250 255 Arg Tyr Tyr Tyr Gln Arg Gly Ile Leu Ala Lys Val Glu Gly Gln Arg 260 265 270 Leu Val Tyr Gln Phe Lys Asp Met Pro Lys Asn Ile Val Val Ile Asp 275 280 285 Asp Asp Lys Ser Glu Thr Cys Asn Glu Asp Leu Ala Gly Thr Thr Asp 290 295 300 Glu Lys Ser Leu Glu Arg Val Ser Leu Ser Ala Glu Ser Leu Leu Lys 305 310 315 320 Ala Ala Ser Ser Val Arg Ser Gly Lys Asn Ser Ser Pro Ile Asn Cys 325 330 335 Ser Arg Ala Glu Lys Gly Val Ala Arg Val Val Asn Ile Thr Ser Pro 340 345 350 Gly His Asp Ala Ser Ser Arg Ser Pro Thr Thr Thr Ala Ser Val Ser 355 360 365 Ala Thr Ala Ala Pro Arg Thr Val Arg Val Ala Met Gln Val Pro Val 370 375 380 Val Met Thr Ser Leu Gly Gln Lys Ile Ser Thr Val Ala Val Gln Ser 385 390 395 400 Val Asn Ala Gly Ala Pro Leu Ile Thr Ser Thr Ser Pro Thr Thr Ala 405 410 415 Thr Ser Pro Lys Val Val Ile Gln Thr Ile Pro Thr Val Met Pro Ala 420 425 430 Ser Thr Glu Asn Gly Asp Lys Ile Thr Met Gln Pro Ala Lys Ile Ile 435 440 445 Thr Ile Pro Ala Thr Gln Leu Ala Gln Cys Gln Leu Gln Thr Lys Ser 450 455 460 Asn Leu Thr Gly Ser Gly Ser Ile Asn Ile Val Gly Thr Pro Leu Ala 465 470 475 480 Val Arg Ala Leu Thr Pro Val Ser Ile Ala His Gly Thr Pro Val Met 485 490 495 Arg Leu Ser Met Pro Thr Gln Gln Ala Ser Gly Gln Thr Pro Pro Arg 500 505 510 Val Ile Ser Ala Val Ile Lys Gly Pro Glu Val Lys Ser Glu Ala Val 515 520 525 Ala Lys Lys Gln Glu His Asp Val Lys Thr Leu Gln Leu Val Glu Glu 530 535 540 Lys Pro Ala Asp Gly Asn Lys Thr Val Thr His Val Val Val Val Ser 545 550 555 560 Ala Pro Ser Ala Ile Ala Leu Pro Val Thr Met Lys Thr Glu Gly Leu 565 570 575 Val Thr Cys Glu Lys 580 <![CDATA[<210> 69]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 69]]> Met Phe Gln Pro Ala Pro Lys Arg Cys Phe Thr Ile Glu Ser Leu Val 1 5 10 15 Ala Lys Asp Ser Pro Leu Pro Ala Ser Arg Ser Glu Asp Pro Ile Arg 20 25 30 Pro Ala Ala Leu Ser Tyr Ala Asn Ser Ser Pro Ile Asn Pro Phe Leu 35 40 45 Asn Gly Phe His Ser Ala Ala Ala Ala Ala Ala Gly Arg Gly Val Tyr 50 55 60 Ser Asn Pro Asp Leu Val Phe Ala Glu Ala Val Ser His Pro Pro Asn 65 70 75 80 Pro Ala Val Pro Val His Pro Val Pro Pro Pro His Ala Leu Ala Ala 85 90 95 His Pro Leu Pro Ser Ser His Ser Pro His Pro Leu Phe Ala Ser Gln 100 105 110 Gln Arg Asp Pro Ser Thr Phe Tyr Pro Trp Leu Ile His Arg Tyr Arg 115 120 125 Tyr Leu Gly His Arg Phe Gln Gly Asn Asp Thr Ser Pro Glu Ser Phe 130 135 140 Leu Leu His Asn Ala Leu Ala Arg Lys Pro Lys Arg Ile Arg Thr Ala 145 150 155 160 Phe Ser Pro Ser Gln Leu Leu Arg Leu Glu His Ala Phe Glu Lys Asn 165 170 175 His Tyr Val Val Gly Ala Glu Arg Lys Gln Leu Ala His Ser Leu Ser 180 185 190 Leu Thr Glu Thr Gln Val Lys Val Trp Phe Gln Asn Arg Arg Thr Lys 195 200 205 Phe Lys Arg Gln Lys Leu Glu Glu Glu Gly Ser Asp Ser Gln Gln Lys 210 215 220 Lys Lys Gly Thr His His Ile Asn Arg Trp Arg Ile Ala Thr Lys Gln 225 230 235 240 Ala Ser Pro Glu Glu Ile Asp Val Thr Ser Asp Asp 245 250 <![CDATA[<210> 70]]> <![CDATA[<211> 423]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 70]]> Met Ser Ser Gln Val Val Gly Ile Glu Pro Leu Tyr Ile Lys Ala Glu 1 5 10 15 Pro Ala Ser Pro Asp Ser Pro Lys Gly Ser Ser Glu Thr Glu Thr Glu 20 25 30 Pro Pro Val Ala Leu Ala Pro Gly Pro Ala Pro Thr Arg Cys Leu Pro 35 40 45 Gly His Lys Glu Glu Glu Asp Gly Glu Gly Ala Gly Pro Gly Glu Gln 50 55 60 Gly Gly Gly Lys Leu Val Leu Ser Ser Leu Pro Lys Arg Leu Cys Leu 65 70 75 80 Val Cys Gly Asp Val Ala Ser Gly Tyr His Tyr Gly Val Ala Ser Cys 85 90 95 Glu Ala Cys Lys Ala Phe Phe Lys Arg Thr Ile Gln Gly Ser Ile Glu 100 105 110 Tyr Ser Cys Pro Ala Ser Asn Glu Cys Glu Ile Thr Lys Arg Arg Arg 115 120 125 Lys Ala Cys Gln Ala Cys Arg Phe Thr Lys Cys Leu Arg Val Gly Met 130 135 140 Leu Lys Glu Gly Val Arg Leu Asp Arg Val Arg Gly Gly Arg Gln Lys 145 150 155 160 Tyr Lys Arg Arg Pro Glu Val Asp Pro Leu Pro Phe Pro Gly Pro Phe 165 170 175 Pro Ala Gly Pro Leu Ala Val Ala Gly Gly Pro Arg Lys Thr Ala Ala 180 185 190 Pro Val Asn Ala Leu Val Ser His Leu Leu Val Val Glu Pro Glu Lys 195 200 205 Leu Tyr Ala Met Pro Asp Pro Ala Gly Pro Asp Gly His Leu Pro Ala 210 215 220 Val Ala Thr Leu Cys Asp Leu Phe Asp Arg Glu Ile Val Val Thr Ile 225 230 235 240 Ser Trp Ala Lys Ser Ile Pro Gly Phe Ser Ser Leu Ser Leu Ser Asp 245 250 255 Gln Met Ser Val Leu Gln Ser Val Trp Met Glu Val Leu Val Leu Gly 260 265 270 Val Ala Gln Arg Ser Leu Pro Leu Gln Asp Glu Leu Ala Phe Ala Glu 275 280 285 Asp Leu Val Leu Asp Glu Glu Gly Ala Arg Ala Ala Gly Leu Gly Glu 290 295 300 Leu Gly Ala Ala Leu Leu Gln Leu Val Arg Arg Leu Gln Ala Leu Arg 305 310 315 320 Leu Glu Arg Glu Glu Tyr Val Leu Leu Lys Ala Leu Ala Leu Ala Asn 325 330 335 Ser Asp Ser Val His Ile Glu Asp Ala Glu Ala Val Glu Gln Leu Arg 340 345 350 Glu Ala Leu His Glu Ala Leu Leu Glu Tyr Glu Ala Gly Arg Ala Gly 355 360 365 Pro Gly Gly Gly Ala Glu Arg Arg Arg Ala Gly Arg Leu Leu Leu Thr 370 375 380 Leu Pro Leu Leu Arg Gln Thr Ala Gly Lys Val Leu Ala His Phe Tyr 385 390 395 400 Gly Val Lys Leu Glu Gly Lys Val Pro Met His Lys Leu Phe Leu Glu 405 410 415 Met Leu Glu Ala Met Met Asp 420 <![CDATA[<210> 71]]> <![CDATA[<211> 469]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 71]]> Met Asn Asp Phe Gly Ile Lys Asn Met Asp Gln Val Ala Pro Val Ala 1 5 10 15 Asn Ser Tyr Arg Gly Thr Leu Lys Arg Gln Pro Ala Phe Asp Thr Phe 20 25 30 Asp Gly Ser Leu Phe Ala Val Phe Pro Ser Leu Asn Glu Glu Gln Thr 35 40 45 Leu Gln Glu Val Pro Thr Gly Leu Asp Ser Ile Ser His Asp Ser Ala 50 55 60 Asn Cys Glu Leu Pro Leu Leu Thr Pro Cys Ser Lys Ala Val Met Ser 65 70 75 80 Gln Ala Leu Lys Ala Thr Phe Ser Gly Phe Lys Lys Glu Gln Arg Arg 85 90 95 Leu Gly Ile Pro Lys Asn Pro Trp Leu Trp Ser Glu Gln Gln Val Cys 100 105 110 Gln Trp Leu Leu Trp Ala Thr Asn Glu Phe Ser Leu Val Asn Val Asn 115 120 125 Leu Gln Arg Phe Gly Met Asn Gly Gln Met Leu Cys Asn Leu Gly Lys 130 135 140 Glu Arg Phe Leu Glu Leu Ala Pro Asp Phe Val Gly Asp Ile Leu Trp 145 150 155 160 Glu His Leu Glu Gln Met Ile Lys Glu Asn Gln Glu Lys Thr Glu Asp 165 170 175 Gln Tyr Glu Glu Asn Ser His Leu Thr Ser Val Pro His Trp Ile Asn 180 185 190 Ser Asn Thr Leu Gly Phe Gly Thr Glu Gln Ala Pro Tyr Gly Met Gln 195 200 205 Thr Gln Asn Tyr Pro Lys Gly Gly Leu Leu Asp Ser Met Cys Pro Ala 210 215 220 Ser Thr Pro Ser Val Leu Ser Ser Glu Gln Glu Phe Gln Met Phe Pro 225 230 235 240 Lys Ser Arg Leu Ser Ser Val Ser Val Thr Tyr Cys Ser Val Ser Gln 245 250 255 Asp Phe Pro Gly Ser Asn Leu Asn Leu Leu Thr Asn Asn Ser Gly Thr 260 265 270 Pro Lys Asp His Asp Ser Pro Glu Asn Gly Ala Asp Ser Phe Glu Ser 275 280 285 Ser Asp Ser Leu Leu Gln Ser Trp Asn Ser Gln Ser Ser Leu Leu Asp 290 295 300 Val Gln Arg Val Pro Ser Phe Glu Ser Phe Glu Asp Asp Cys Ser Gln 305 310 315 320 Ser Leu Cys Leu Asn Lys Pro Thr Met Ser Phe Lys Asp Tyr Ile Gln 325 330 335 Glu Arg Ser Asp Pro Val Glu Gln Gly Lys Pro Val Ile Pro Ala Ala 340 345 350 Val Leu Ala Gly Phe Thr Gly Ser Gly Pro Ile Gln Leu Trp Gln Phe 355 360 365 Leu Leu Glu Leu Leu Ser Asp Lys Ser Cys Gln Ser Phe Ile Ser Trp 370 375 380 Thr Gly Asp Gly Trp Glu Phe Lys Leu Ala Asp Pro Asp Glu Val Ala 385 390 395 400 Arg Arg Trp Gly Lys Arg Lys Asn Lys Pro Lys Met Asn Tyr Glu Lys 405 410 415 Leu Ser Arg Gly Leu Arg Tyr Tyr Tyr Asp Lys Asn Ile Ile His Lys 420 425 430 Thr Ser Gly Lys Arg Tyr Val Tyr Arg Phe Val Cys Asp Leu Gln Asn 435 440 445 Leu Leu Gly Phe Thr Pro Glu Glu Leu His Ala Ile Leu Gly Val Gln 450 455 460 Pro Asp Thr Glu Asp 465 <![CDATA[<210> 72]]> <![CDATA[<211> 380]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 72]]> Met Met Phe Ser Gly Phe Asn Ala Asp Tyr Glu Ala Ser Ser Ser Arg 1 5 10 15 Cys Ser Ser Ala Ser Pro Ala Gly Asp Ser Leu Ser Tyr Tyr His Ser 20 25 30 Pro Ala Asp Ser Phe Ser Ser Met Gly Ser Pro Val Asn Ala Gln Asp 35 40 45 Phe Cys Thr Asp Leu Ala Val Ser Ser Ala Asn Phe Ile Pro Thr Val 50 55 60 Thr Ala Ile Ser Thr Ser Pro Asp Leu Gln Trp Leu Val Gln Pro Ala 65 70 75 80 Leu Val Ser Ser Val Ala Pro Ser Gln Thr Arg Ala Pro His Pro Phe 85 90 95 Gly Val Pro Ala Pro Ser Ala Gly Ala Tyr Ser Arg Ala Gly Val Val 100 105 110 Lys Thr Met Thr Gly Gly Arg Ala Gln Ser Ile Gly Arg Arg Gly Lys 115 120 125 Val Glu Gln Leu Ser Pro Glu Glu Glu Glu Lys Arg Arg Ile Arg Arg 130 135 140 Glu Arg Asn Lys Met Ala Ala Ala Lys Cys Arg Asn Arg Arg Arg Glu 145 150 155 160 Leu Thr Asp Thr Leu Gln Ala Glu Thr Asp Gln Leu Glu Asp Glu Lys 165 170 175 Ser Ala Leu Gln Thr Glu Ile Ala Asn Leu Leu Lys Glu Lys Glu Lys 180 185 190 Leu Glu Phe Ile Leu Ala Ala His Arg Pro Ala Cys Lys Ile Pro Asp 195 200 205 Asp Leu Gly Phe Pro Glu Glu Met Ser Val Ala Ser Leu Asp Leu Thr 210 215 220 Gly Gly Leu Pro Glu Val Ala Thr Pro Glu Ser Glu Glu Ala Phe Thr 225 230 235 240 Leu Pro Leu Leu Asn Asp Pro Glu Pro Lys Pro Ser Val Glu Pro Val 245 250 255 Lys Ser Ile Ser Ser Met Glu Leu Lys Thr Glu Pro Phe Asp Asp Phe 260 265 270 Leu Phe Pro Ala Ser Ser Arg Pro Ser Gly Ser Glu Thr Ala Arg Ser 275 280 285 Val Pro Asp Met Asp Leu Ser Gly Ser Phe Tyr Ala Ala Asp Trp Glu 290 295 300 Pro Leu His Ser Gly Ser Leu Gly Met Gly Pro Met Ala Thr Glu Leu 305 310 315 320 Glu Pro Leu Cys Thr Pro Val Val Thr Cys Thr Pro Ser Cys Thr Ala 325 330 335 Tyr Thr Ser Ser Phe Val Phe Thr Tyr Pro Glu Ala Asp Ser Phe Pro 340 345 350 Ser Cys Ala Ala Ala His Arg Lys Gly Ser Ser Ser Asn Glu Pro Ser 355 360 365 Ser Asp Ser Leu Ser Ser Pro Thr Leu Leu Ala Leu 370 375 380 <![CDATA[<210> 73]]> <![CDATA[<211> 338]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 73]]> Met Phe Gln Ala Phe Pro Gly Asp Tyr Asp Ser Gly Ser Arg Cys Ser 1 5 10 15 Ser Ser Pro Ser Ala Glu Ser Gln Tyr Leu Ser Ser Val Asp Ser Phe 20 25 30 Gly Ser Pro Pro Thr Ala Ala Ala Ser Gln Glu Cys Ala Gly Leu Gly 35 40 45 Glu Met Pro Gly Ser Phe Val Pro Thr Val Thr Ala Ile Thr Thr Ser 50 55 60 Gln Asp Leu Gln Trp Leu Val Gln Pro Thr Leu Ile Ser Ser Met Ala 65 70 75 80 Gln Ser Gln Gly Gln Pro Leu Ala Ser Gln Pro Pro Val Val Asp Pro 85 90 95 Tyr Asp Met Pro Gly Thr Ser Tyr Ser Thr Pro Gly Met Ser Gly Tyr 100 105 110 Ser Ser Gly Gly Ala Ser Gly Ser Gly Gly Pro Ser Thr Ser Gly Thr 115 120 125 Thr Ser Gly Pro Gly Pro Ala Arg Pro Ala Arg Ala Arg Pro Arg Arg 130 135 140 Pro Arg Glu Glu Thr Leu Thr Pro Glu Glu Glu Glu Lys Arg Arg Val 145 150 155 160 Arg Arg Glu Arg Asn Lys Leu Ala Ala Ala Lys Cys Arg Asn Arg Arg 165 170 175 Arg Glu Leu Thr Asp Arg Leu Gln Ala Glu Thr Asp Gln Leu Glu Glu 180 185 190 Glu Lys Ala Glu Leu Glu Ser Glu Ile Ala Glu Leu Gln Lys Glu Lys 195 200 205 Glu Arg Leu Glu Phe Val Leu Val Ala His Lys Pro Gly Cys Lys Ile 210 215 220 Pro Tyr Glu Glu Gly Pro Gly Pro Gly Pro Leu Ala Glu Val Arg Asp 225 230 235 240 Leu Pro Gly Ser Ala Pro Ala Lys Glu Asp Gly Phe Ser Trp Leu Leu 245 250 255 Pro Pro Pro Pro Pro Pro Pro Leu Pro Phe Gln Thr Ser Gln Asp Ala 260 265 270 Pro Pro Asn Leu Thr Ala Ser Leu Phe Thr His Ser Glu Val Gln Val 275 280 285 Leu Gly Asp Pro Phe Pro Val Val Asn Pro Ser Tyr Thr Ser Ser Phe 290 295 300 Val Leu Thr Cys Pro Glu Val Ser Ala Phe Ala Gly Ala Gln Arg Thr 305 310 315 320 Ser Gly Ser Asp Gln Pro Ser Asp Pro Leu Asn Ser Pro Ser Leu Leu 325 330 335 Ala Leu <![CDATA[<210> 74]]> <![CDATA[<211> 326]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 74]]> Met Tyr Gln Asp Tyr Pro Gly Asn Phe Asp Thr Ser Ser Arg Gly Ser 1 5 10 15 Ser Gly Ser Pro Ala His Ala Glu Ser Tyr Ser Ser Gly Gly Gly Gly 20 25 30 Gln Gln Lys Phe Arg Val Asp Met Pro Gly Ser Gly Ser Ala Phe Ile 35 40 45 Pro Thr Ile Asn Ala Ile Thr Thr Ser Gln Asp Leu Gln Trp Met Val 50 55 60 Gln Pro Thr Val Ile Thr Ser Met Ser Asn Pro Tyr Pro Arg Ser His 65 70 75 80 Pro Tyr Ser Pro Leu Pro Gly Leu Ala Ser Val Pro Gly His Met Ala 85 90 95 Leu Pro Arg Pro Gly Val Ile Lys Thr Ile Gly Thr Thr Val Gly Arg 100 105 110 Arg Arg Arg Asp Glu Gln Leu Ser Pro Glu Glu Glu Glu Lys Arg Arg 115 120 125 Ile Arg Arg Glu Arg Asn Lys Leu Ala Ala Ala Lys Cys Arg Asn Arg 130 135 140 Arg Arg Glu Leu Thr Glu Lys Leu Gln Ala Glu Thr Glu Glu Leu Glu 145 150 155 160 Glu Glu Lys Ser Gly Leu Gln Lys Glu Ile Ala Glu Leu Gln Lys Glu 165 170 175 Lys Glu Lys Leu Glu Phe Met Leu Val Ala His Gly Pro Val Cys Lys 180 185 190 Ile Ser Pro Glu Glu Arg Arg Ser Pro Pro Ala Pro Gly Leu Gln Pro 195 200 205 Met Arg Ser Gly Gly Gly Ser Val Gly Ala Val Val Val Lys Gln Glu 210 215 220 Pro Leu Glu Glu Asp Ser Pro Ser Ser Ser Ser Ala Gly Leu Asp Lys 225 230 235 240 Ala Gln Arg Ser Val Ile Lys Pro Ile Ser Ile Ala Gly Gly Phe Tyr 245 250 255 Gly Glu Glu Pro Leu His Thr Pro Ile Val Val Thr Ser Thr Pro Ala 260 265 270 Val Thr Pro Gly Thr Ser Asn Leu Val Phe Thr Tyr Pro Ser Val Leu 275 280 285 Glu Gln Glu Ser Pro Ala Ser Pro Ser Glu Ser Cys Ser Lys Ala His 290 295 300 Arg Arg Ser Ser Ser Ser Gly Asp Gln Ser Ser Asp Ser Leu Asn Ser 305 310 315 320 Pro Thr Leu Leu Ala Leu 325 <![CDATA[<210> 75]]> <![CDATA[<211> 365]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 75]]> Met Asp Pro Pro Ala Val Val Ala Glu Ser Val Ser Ser Leu Thr Ile 1 5 10 15 Ala Asp Ala Phe Ile Ala Ala Gly Glu Ser Ser Ala Pro Thr Pro Pro 20 25 30 Arg Pro Ala Leu Pro Arg Arg Phe Ile Cys Ser Phe Pro Asp Cys Ser 35 40 45 Ala Asn Tyr Ser Lys Ala Trp Lys Leu Asp Ala His Leu Cys Lys His 50 55 60 Thr Gly Glu Arg Pro Phe Val Cys Asp Tyr Glu Gly Cys Gly Lys Ala 65 70 75 80 Phe Ile Arg Asp Tyr His Leu Ser Arg His Ile Leu Thr His Thr Gly 85 90 95 Glu Lys Pro Phe Val Cys Ala Ala Asn Gly Cys Asp Gln Lys Phe Asn 100 105 110 Thr Lys Ser Asn Leu Lys Lys His Phe Glu Arg Lys His Glu Asn Gln 115 120 125 Gln Lys Gln Tyr Ile Cys Ser Phe Glu Asp Cys Lys Lys Thr Phe Lys 130 135 140 Lys His Gln Gln Leu Lys Ile His Gln Cys Gln His Thr Asn Glu Pro 145 150 155 160 Leu Phe Lys Cys Thr Gln Glu Gly Cys Gly Lys His Phe Ala Ser Pro 165 170 175 Ser Lys Leu Lys Arg His Ala Lys Ala His Glu Gly Tyr Val Cys Gln 180 185 190 Lys Gly Cys Ser Phe Val Ala Lys Thr Trp Thr Glu Leu Leu Lys His 195 200 205 Val Arg Glu Thr His Lys Glu Glu Ile Leu Cys Glu Val Cys Arg Lys 210 215 220 Thr Phe Lys Arg Lys Asp Tyr Leu Lys Gln His Met Lys Thr His Ala 225 230 235 240 Pro Glu Arg Asp Val Cys Arg Cys Pro Arg Glu Gly Cys Gly Arg Thr 245 250 255 Tyr Thr Thr Val Phe Asn Leu Gln Ser His Ile Leu Ser Phe His Glu 260 265 270 Glu Ser Arg Pro Phe Val Cys Glu His Ala Gly Cys Gly Lys Thr Phe 275 280 285 Ala Met Lys Gln Ser Leu Thr Arg His Ala Val Val His Asp Pro Asp 290 295 300 Lys Lys Lys Met Lys Leu Lys Val Lys Lys Ser Arg Glu Lys Arg Ser 305 310 315 320 Leu Ala Ser His Leu Ser Gly Tyr Ile Pro Pro Lys Arg Lys Gln Gly 325 330 335 Gln Gly Leu Ser Leu Cys Gln Asn Gly Glu Ser Pro Asn Cys Val Glu 340 345 350 Asp Lys Met Leu Ser Thr Val Ala Val Leu Thr Leu Gly 355 360 365 <![CDATA[<210> 76]]> <![CDATA[<211> 826]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 76]]> Met Glu Gly Ala Gly Gly Ala Asn Asp Lys Lys Lys Ile Ser Ser Glu 1 5 10 15 Arg Arg Lys Glu Lys Ser Arg Asp Ala Ala Arg Ser Arg Arg Ser Lys 20 25 30 Glu Ser Glu Val Phe Tyr Glu Leu Ala His Gln Leu Pro Leu Pro His 35 40 45 Asn Val Ser Ser His Leu Asp Lys Ala Ser Val Met Arg Leu Thr Ile 50 55 60 Ser Tyr Leu Arg Val Arg Lys Leu Leu Asp Ala Gly Asp Leu Asp Ile 65 70 75 80 Glu Asp Asp Met Lys Ala Gln Met Asn Cys Phe Tyr Leu Lys Ala Leu 85 90 95 Asp Gly Phe Val Met Val Leu Thr Asp Asp Gly Asp Met Ile Tyr Ile 100 105 110 Ser Asp Asn Val Asn Lys Tyr Met Gly Leu Thr Gln Phe Glu Leu Thr 115 120 125 Gly His Ser Val Phe Asp Phe Thr His Pro Cys Asp His Glu Glu Met 130 135 140 Arg Glu Met Leu Thr His Arg Asn Gly Leu Val Lys Lys Gly Lys Glu 145 150 155 160 Gln Asn Thr Gln Arg Ser Phe Phe Leu Arg Met Lys Cys Thr Leu Thr 165 170 175 Ser Arg Gly Arg Thr Met Asn Ile Lys Ser Ala Thr Trp Lys Val Leu 180 185 190 His Cys Thr Gly His Ile His Val Tyr Asp Thr Asn Ser Asn Gln Pro 195 200 205 Gln Cys Gly Tyr Lys Lys Pro Pro Met Thr Cys Leu Val Leu Ile Cys 210 215 220 Glu Pro Ile Pro His Pro Ser Asn Ile Glu Ile Pro Leu Asp Ser Lys 225 230 235 240 Thr Phe Leu Ser Arg His Ser Leu Asp Met Lys Phe Ser Tyr Cys Asp 245 250 255 Glu Arg Ile Thr Glu Leu Met Gly Tyr Glu Pro Glu Glu Leu Leu Gly 260 265 270 Arg Ser Ile Tyr Glu Tyr Tyr His Ala Leu Asp Ser Asp His Leu Thr 275 280 285 Lys Thr His His Asp Met Phe Thr Lys Gly Gln Val Thr Thr Gly Gln 290 295 300 Tyr Arg Met Leu Ala Lys Arg Gly Gly Tyr Val Trp Val Glu Thr Gln 305 310 315 320 Ala Thr Val Ile Tyr Asn Thr Lys Asn Ser Gln Pro Gln Cys Ile Val 325 330 335 Cys Val Asn Tyr Val Val Ser Gly Ile Ile Gln His Asp Leu Ile Phe 340 345 350 Ser Leu Gln Gln Thr Glu Cys Val Leu Lys Pro Val Glu Ser Ser Asp 355 360 365 Met Lys Met Thr Gln Leu Phe Thr Lys Val Glu Ser Glu Asp Thr Ser 370 375 380 Ser Leu Phe Asp Lys Leu Lys Lys Glu Pro Asp Ala Leu Thr Leu Leu 385 390 395 400 Ala Pro Ala Ala Gly Asp Thr Ile Ile Ser Leu Asp Phe Gly Ser Asn 405 410 415 Asp Thr Glu Thr Asp Asp Gln Gln Leu Glu Glu Val Pro Leu Tyr Asn 420 425 430 Asp Val Met Leu Pro Ser Pro Asn Glu Lys Leu Gln Asn Ile Asn Leu 435 440 445 Ala Met Ser Pro Leu Pro Thr Ala Glu Thr Pro Lys Pro Leu Arg Ser 450 455 460 Ser Ala Asp Pro Ala Leu Asn Gln Glu Val Ala Leu Lys Leu Glu Pro 465 470 475 480 Asn Pro Glu Ser Leu Glu Leu Ser Phe Thr Met Pro Gln Ile Gln Asp 485 490 495 Gln Thr Pro Ser Pro Ser Asp Gly Ser Thr Arg Gln Ser Ser Pro Glu 500 505 510 Pro Asn Ser Pro Ser Glu Tyr Cys Phe Tyr Val Asp Ser Asp Met Val 515 520 525 Asn Glu Phe Lys Leu Glu Leu Val Glu Lys Leu Phe Ala Glu Asp Thr 530 535 540 Glu Ala Lys Asn Pro Phe Ser Thr Gln Asp Thr Asp Leu Asp Leu Glu 545 550 555 560 Met Leu Ala Pro Tyr Ile Pro Met Asp Asp Asp Phe Gln Leu Arg Ser 565 570 575 Phe Asp Gln Leu Ser Pro Leu Glu Ser Ser Ser Ala Ser Pro Glu Ser 580 585 590 Ala Ser Pro Gln Ser Thr Val Thr Val Phe Gln Gln Thr Gln Ile Gln 595 600 605 Glu Pro Thr Ala Asn Ala Thr Thr Thr Thr Ala Thr Thr Asp Glu Leu 610 615 620 Lys Thr Val Thr Lys Asp Arg Met Glu Asp Ile Lys Ile Leu Ile Ala 625 630 635 640 Ser Pro Ser Pro Thr His Ile His Lys Glu Thr Thr Ser Ala Thr Ser 645 650 655 Ser Pro Tyr Arg Asp Thr Gln Ser Arg Thr Ala Ser Pro Asn Arg Ala 660 665 670 Gly Lys Gly Val Ile Glu Gln Thr Glu Lys Ser His Pro Arg Ser Pro 675 680 685 Asn Val Leu Ser Val Ala Leu Ser Gln Arg Thr Thr Val Pro Glu Glu 690 695 700 Glu Leu Asn Pro Lys Ile Leu Ala Leu Gln Asn Ala Gln Arg Lys Arg 705 710 715 720 Lys Met Glu His Asp Gly Ser Leu Phe Gln Ala Val Gly Ile Gly Thr 725 730 735 Leu Leu Gln Gln Pro Asp Asp His Ala Ala Thr Thr Ser Leu Ser Trp 740 745 750 Lys Arg Val Lys Gly Cys Lys Ser Ser Glu Gln Asn Gly Met Glu Gln 755 760 765 Lys Thr Ile Ile Leu Ile Pro Ser Asp Leu Ala Cys Arg Leu Leu Gly 770 775 780 Gln Ser Met Asp Glu Ser Gly Leu Pro Gln Leu Thr Ser Tyr Asp Cys 785 790 795 800 Glu Val Asn Ala Pro Ile Gln Gly Ser Arg Asn Leu Leu Gln Gly Glu 805 810 815 Glu Leu Leu Arg Ala Leu Asp Gln Val Asn 820 825 <![CDATA[<210> 77]]> <![CDATA[<211> 331]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 77]]> Met Thr Ala Lys Met Glu Thr Thr Phe Tyr Asp Asp Ala Leu Asn Ala 1 5 10 15 Ser Phe Leu Pro Ser Glu Ser Gly Pro Tyr Gly Tyr Ser Asn Pro Lys 20 25 30 Ile Leu Lys Gln Ser Met Thr Leu Asn Leu Ala Asp Pro Val Gly Ser 35 40 45 Leu Lys Pro His Leu Arg Ala Lys Asn Ser Asp Leu Leu Thr Ser Pro 50 55 60 Asp Val Gly Leu Leu Lys Leu Ala Ser Pro Glu Leu Glu Arg Leu Ile 65 70 75 80 Ile Gln Ser Ser Asn Gly His Ile Thr Thr Thr Pro Thr Pro Thr Gln 85 90 95 Phe Leu Cys Pro Lys Asn Val Thr Asp Glu Gln Glu Gly Phe Ala Glu 100 105 110 Gly Phe Val Arg Ala Leu Ala Glu Leu His Ser Gln Asn Thr Leu Pro 115 120 125 Ser Val Thr Ser Ala Ala Gln Pro Val Asn Gly Ala Gly Met Val Ala 130 135 140 Pro Ala Val Ala Ser Val Ala Gly Gly Ser Gly Ser Gly Gly Phe Ser 145 150 155 160 Ala Ser Leu His Ser Glu Pro Pro Val Tyr Ala Asn Leu Ser Asn Phe 165 170 175 Asn Pro Gly Ala Leu Ser Ser Gly Gly Gly Ala Pro Ser Tyr Gly Ala 180 185 190 Ala Gly Leu Ala Phe Pro Ala Gln Pro Gln Gln Gln Gln Gln Pro Pro 195 200 205 His His Leu Pro Gln Gln Met Pro Val Gln His Pro Arg Leu Gln Ala 210 215 220 Leu Lys Glu Glu Pro Gln Thr Val Pro Glu Met Pro Gly Glu Thr Pro 225 230 235 240 Pro Leu Ser Pro Ile Asp Met Glu Ser Gln Glu Arg Ile Lys Ala Glu 245 250 255 Arg Lys Arg Met Arg Asn Arg Ile Ala Ala Ser Lys Cys Arg Lys Arg 260 265 270 Lys Leu Glu Arg Ile Ala Arg Leu Glu Glu Lys Val Lys Thr Leu Lys 275 280 285 Ala Gln Asn Ser Glu Leu Ala Ser Thr Ala Asn Met Leu Arg Glu Gln 290 295 300 Val Ala Gln Leu Lys Gln Lys Val Met Asn His Val Asn Ser Gly Cys 305 310 315 320 Gln Leu Met Leu Thr Gln Gln Leu Gln Thr Phe 325 330 <![CDATA[<210> 78]]> <![CDATA[<211> 347]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 78]]> Met Cys Thr Lys Met Glu Gln Pro Phe Tyr His Asp Asp Ser Tyr Thr 1 5 10 15 Ala Thr Gly Tyr Gly Arg Ala Pro Gly Gly Leu Ser Leu His Asp Tyr 20 25 30 Lys Leu Leu Lys Pro Ser Leu Ala Val Asn Leu Ala Asp Pro Tyr Arg 35 40 45 Ser Leu Lys Ala Pro Gly Ala Arg Gly Pro Gly Pro Glu Gly Gly Gly 50 55 60 Gly Gly Ser Tyr Phe Ser Gly Gln Gly Ser Asp Thr Gly Ala Ser Leu 65 70 75 80 Lys Leu Ala Ser Ser Glu Leu Glu Arg Leu Ile Val Pro Asn Ser Asn 85 90 95 Gly Val Ile Thr Thr Thr Pro Thr Pro Pro Gly Gln Tyr Phe Tyr Pro 100 105 110 Arg Gly Gly Gly Ser Gly Gly Gly Ala Gly Gly Ala Gly Gly Gly Val 115 120 125 Thr Glu Glu Gln Glu Gly Phe Ala Asp Gly Phe Val Lys Ala Leu Asp 130 135 140 Asp Leu His Lys Met Asn His Val Thr Pro Pro Asn Val Ser Leu Gly 145 150 155 160 Ala Thr Gly Gly Pro Pro Ala Gly Pro Gly Gly Val Tyr Ala Gly Pro 165 170 175 Glu Pro Pro Pro Val Tyr Thr Asn Leu Ser Ser Tyr Ser Pro Ala Ser 180 185 190 Ala Ser Ser Gly Gly Ala Gly Ala Ala Val Gly Thr Gly Ser Ser Tyr 195 200 205 Pro Thr Thr Thr Ile Ser Tyr Leu Pro His Ala Pro Pro Phe Ala Gly 210 215 220 Gly His Pro Ala Gln Leu Gly Leu Gly Arg Gly Ala Ser Thr Phe Lys 225 230 235 240 Glu Glu Pro Gln Thr Val Pro Glu Ala Arg Ser Arg Asp Ala Thr Pro 245 250 255 Pro Val Ser Pro Ile Asn Met Glu Asp Gln Glu Arg Ile Lys Val Glu 260 265 270 Arg Lys Arg Leu Arg Asn Arg Leu Ala Ala Thr Lys Cys Arg Lys Arg 275 280 285 Lys Leu Glu Arg Ile Ala Arg Leu Glu Asp Lys Val Lys Thr Leu Lys 290 295 300 Ala Glu Asn Ala Gly Leu Ser Ser Thr Ala Gly Leu Leu Arg Glu Gln 305 310 315 320 Val Ala Gln Leu Lys Gln Lys Val Met Thr His Val Ser Asn Gly Cys 325 330 335 Gln Leu Leu Leu Gly Val Lys Gly His Ala Phe 340 345 <![CDATA[<210> 79]]> <![CDATA[<211> 304]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 79]]> Met Met Lys Lys Asp Ala Leu Thr Leu Ser Leu Ser Glu Gln Val Ala 1 5 10 15 Ala Ala Leu Lys Pro Ala Ala Ala Pro Pro Pro Thr Pro Leu Arg Ala 20 25 30 Asp Gly Ala Pro Ser Ala Ala Pro Pro Asp Gly Leu Leu Ala Ser Pro 35 40 45 Asp Leu Gly Leu Leu Lys Leu Ala Ser Pro Glu Leu Glu Arg Leu Ile 50 55 60 Ile Gln Ser Asn Gly Leu Val Thr Thr Thr Pro Thr Ser Ser Gln Phe 65 70 75 80 Leu Tyr Pro Lys Val Ala Ala Ser Glu Glu Gln Glu Phe Ala Glu Gly 85 90 95 Phe Val Lys Ala Leu Glu Asp Leu His Lys Gln Asn Gln Leu Gly Ala 100 105 110 Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Pro Ser Gly 115 120 125 Thr Ala Thr Gly Ser Ala Pro Pro Gly Glu Leu Ala Pro Ala Ala Ala 130 135 140 Ala Pro Glu Ala Pro Val Tyr Ala Asn Leu Ser Ser Tyr Ala Gly Gly 145 150 155 160 Ala Gly Gly Ala Gly Gly Ala Ala Thr Val Ala Phe Ala Ala Glu Pro 165 170 175 Val Pro Phe Pro Pro Pro Pro Pro Pro Gly Ala Leu Gly Pro Pro Arg 180 185 190 Leu Ala Ala Leu Lys Asp Glu Pro Gln Thr Val Pro Asp Val Pro Ser 195 200 205 Phe Gly Glu Ser Pro Pro Leu Ser Pro Ile Asp Met Asp Thr Gln Glu 210 215 220 Arg Ile Lys Ala Glu Arg Lys Arg Leu Arg Asn Arg Ile Ala Ala Ser 225 230 235 240 Lys Cys Arg Lys Arg Lys Leu Glu Arg Ile Ser Arg Leu Glu Glu Lys 245 250 255 Val Lys Thr Leu Lys Ser Gln Asn Thr Glu Leu Ala Ser Thr Ala Ser 260 265 270 Leu Leu Arg Glu Gln Val Ala Gln Leu Lys Gln Lys Val Leu Ser His 275 280 285 Val Asn Ser Gly Cys Gln Leu Leu Pro Gln His Gln Val Pro Ala Tyr 290 295 300 <![CDATA[<210> 80]]> <![CDATA[<211> 480]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 80]]> Met Leu Asn Phe Gly Ala Ser Leu Gln Gln Thr Ala Glu Glu Arg Met 1 5 10 15 Glu Met Ile Ser Glu Arg Pro Lys Glu Ser Met Tyr Ser Trp Asn Lys 20 25 30 Thr Ala Glu Lys Ser Asp Phe Glu Ala Val Glu Ala Leu Met Ser Met 35 40 45 Ser Cys Ser Trp Lys Ser Asp Phe Lys Lys Tyr Val Glu Asn Arg Pro 50 55 60 Val Thr Pro Val Ser Asp Leu Ser Glu Glu Glu Asn Leu Leu Pro Gly 65 70 75 80 Thr Pro Asp Phe His Thr Ile Pro Ala Phe Cys Leu Thr Pro Pro Tyr 85 90 95 Ser Pro Ser Asp Phe Glu Pro Ser Gln Val Ser Asn Leu Met Ala Pro 100 105 110 Ala Pro Ser Thr Val His Phe Lys Ser Leu Ser Asp Thr Ala Lys Pro 115 120 125 His Ile Ala Ala Pro Phe Lys Glu Glu Glu Lys Ser Pro Val Ser Ala 130 135 140 Pro Lys Leu Pro Lys Ala Gln Ala Thr Ser Val Ile Arg His Thr Ala 145 150 155 160 Asp Ala Gln Leu Cys Asn His Gln Thr Cys Pro Met Lys Ala Ala Ser 165 170 175 Ile Leu Asn Tyr Gln Asn Asn Ser Phe Arg Arg Arg Thr His Leu Asn 180 185 190 Val Glu Ala Ala Arg Lys Asn Ile Pro Cys Ala Ala Val Ser Pro Asn 195 200 205 Arg Ser Lys Cys Glu Arg Asn Thr Val Ala Asp Val Asp Glu Lys Ala 210 215 220 Ser Ala Ala Leu Tyr Asp Phe Ser Val Pro Ser Ser Glu Thr Val Ile 225 230 235 240 Cys Arg Ser Gln Pro Ala Pro Val Ser Pro Gln Gln Lys Ser Val Leu 245 250 255 Val Ser Pro Pro Ala Val Ser Ala Gly Gly Val Pro Pro Met Pro Val 260 265 270 Ile Cys Gln Met Val Pro Leu Pro Ala Asn Asn Pro Val Val Thr Thr 275 280 285 Val Val Pro Ser Thr Pro Pro Ser Gln Pro Pro Ala Val Cys Pro Pro 290 295 300 Val Val Phe Met Gly Thr Gln Val Pro Lys Gly Ala Val Met Phe Val 305 310 315 320 Val Pro Gln Pro Val Val Gln Ser Ser Lys Pro Pro Val Val Ser Pro 325 330 335 Asn Gly Thr Arg Leu Ser Pro Ile Ala Pro Ala Pro Gly Phe Ser Pro 340 345 350 Ser Ala Ala Lys Val Thr Pro Gln Ile Asp Ser Ser Arg Ile Arg Ser 355 360 365 His Ile Cys Ser His Pro Gly Cys Gly Lys Thr Tyr Phe Lys Ser Ser 370 375 380 His Leu Lys Ala His Thr Arg Thr His Thr Gly Glu Lys Pro Phe Ser 385 390 395 400 Cys Ser Trp Lys Gly Cys Glu Arg Arg Phe Ala Arg Ser Asp Glu Leu 405 410 415 Ser Arg His Arg Arg Thr His Thr Gly Glu Lys Lys Phe Ala Cys Pro 420 425 430 Met Cys Asp Arg Arg Phe Met Arg Ser Asp His Leu Thr Lys His Ala 435 440 445 Arg Arg His Leu Ser Ala Lys Lys Leu Pro Asn Trp Gln Met Glu Val 450 455 460 Ser Lys Leu Asn Asp Ile Ala Leu Pro Pro Thr Pro Ala Pro Thr Gln 465 470 475 480 <![CDATA[<210> 81]]> <![CDATA[<211> 244]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 81]]> Met Ser Ala Ala Ala Tyr Met Asp Phe Val Ala Ala Gln Cys Leu Val 1 5 10 15 Ser Ile Ser Asn Arg Ala Ala Val Pro Glu His Gly Val Ala Pro Asp 20 25 30 Ala Glu Arg Leu Arg Leu Pro Glu Arg Glu Val Thr Lys Glu His Gly 35 40 45 Asp Pro Gly Asp Thr Trp Lys Asp Tyr Cys Thr Leu Val Thr Ile Ala 50 55 60 Lys Ser Leu Leu Asp Leu Asn Lys Tyr Arg Pro Ile Gln Thr Pro Ser 65 70 75 80 Val Cys Ser Asp Ser Leu Glu Ser Pro Asp Glu Asp Met Gly Ser Asp 85 90 95 Ser Asp Val Thr Thr Glu Ser Gly Ser Ser Pro Ser His Ser Pro Glu 100 105 110 Glu Arg Gln Asp Pro Gly Ser Ala Pro Ser Pro Leu Ser Leu Leu His 115 120 125 Pro Gly Val Ala Ala Lys Gly Lys His Ala Ser Glu Lys Arg His Lys 130 135 140 Cys Pro Tyr Ser Gly Cys Gly Lys Val Tyr Gly Lys Ser Ser His Leu 145 150 155 160 Lys Ala His Tyr Arg Val His Thr Gly Glu Arg Pro Phe Pro Cys Thr 165 170 175 Trp Pro Asp Cys Leu Lys Lys Phe Ser Arg Ser Asp Glu Leu Thr Arg 180 185 190 His Tyr Arg Thr His Thr Gly Glu Lys Gln Phe Arg Cys Pro Leu Cys 195 200 205 Glu Lys Arg Phe Met Arg Ser Asp His Leu Thr Lys His Ala Arg Arg 210 215 220 His Thr Glu Phe His Pro Ser Met Ile Lys Arg Ser Lys Lys Ala Leu 225 230 235 240 Ala Asn Ala Leu <![CDATA[<210> 82]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 82]]> Met Glu Arg Lys Ser Pro Ser Gly Lys Lys Phe Arg Ser Lys Pro Gln 1 5 10 15 Leu Ala Arg Tyr Leu Gly Gly Ser Met Asp Leu Ser Thr Phe Asp Phe 20 25 30 Arg Thr Gly Lys Met Leu Met Ser Lys Met Asn Lys Ser Arg Gln Arg 35 40 45 Val Arg Tyr Asp Ser Ser Asn Gln Val Lys Gly Lys Pro Asp Leu Asn 50 55 60 Thr Ala Leu Pro Val Arg Gln Thr Ala Ser Ile Phe Lys Gln Pro Val 65 70 75 80 Thr Lys Ile Thr Asn His Pro Ser Asn Lys Val Lys Ser Asp Pro Gln 85 90 95 Lys Ala Val Asp Gln Pro Arg Gln Leu Phe Trp Glu Lys Lys Leu Ser 100 105 110 Gly Leu Asn Ala Phe Asp Ile Ala Glu Glu Leu Val Lys Thr Met Asp 115 120 125 Leu Pro Lys Gly Leu Gln Gly Val Gly Pro Gly Cys Thr Asp Glu Thr 130 135 140 Leu Leu Ser Ala Ile Ala Ser Ala Leu His Thr Ser Thr Met Pro Ile 145 150 155 160 Thr Gly Gln Leu Ser Ala Ala Val Glu Lys Asn Pro Gly Val Trp Leu 165 170 175 Asn Thr Thr Gln Pro Leu Cys Lys Ala Phe Met Val Thr Asp Glu Asp 180 185 190 Ile Arg Lys Gln Glu Glu Leu Val Gln Gln Val Arg Lys Arg Leu Glu 195 200 205 Glu Ala Leu Met Ala Asp Met Leu Ala His Val Glu Glu Leu Ala Arg 210 215 220 Asp Gly Glu Ala Pro Leu Asp Lys Ala Cys Ala Glu Asp Asp Asp Glu 225 230 235 240 Glu Asp Glu Glu Glu Glu Glu Glu Glu Pro Asp Pro Asp Pro Glu Met 245 250 255 Glu His Val <![CDATA[<210> 83]]> <![CDATA[<211> 772]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 83]]> Met Leu Ser Leu Lys Lys Tyr Leu Thr Glu Gly Leu Leu Gln Phe Thr 1 5 10 15 Ile Leu Leu Ser Leu Ile Gly Val Arg Val Asp Val Asp Thr Tyr Leu 20 25 30 Thr Ser Gln Leu Pro Pro Leu Arg Glu Ile Ile Leu Gly Pro Ser Ser 35 40 45 Ala Tyr Thr Gln Thr Gln Phe His Asn Leu Arg Asn Thr Leu Asp Gly 50 55 60 Tyr Gly Ile His Pro Lys Ser Ile Asp Leu Asp Asn Tyr Phe Thr Ala 65 70 75 80 Arg Arg Leu Leu Ser Gln Val Arg Ala Leu Asp Arg Phe Gln Val Pro 85 90 95 Thr Thr Glu Val Asn Ala Trp Leu Val His Arg Asp Pro Glu Gly Ser 100 105 110 Val Ser Gly Ser Gln Pro Asn Ser Gly Leu Ala Leu Glu Ser Ser Ser 115 120 125 Gly Leu Gln Asp Val Thr Gly Pro Asp Asn Gly Val Arg Glu Ser Glu 130 135 140 Thr Glu Gln Gly Phe Gly Glu Asp Leu Glu Asp Leu Gly Ala Val Ala 145 150 155 160 Pro Pro Val Ser Gly Asp Leu Thr Lys Glu Asp Ile Asp Leu Ile Asp 165 170 175 Ile Leu Trp Arg Gln Asp Ile Asp Leu Gly Ala Gly Arg Glu Val Phe 180 185 190 Asp Tyr Ser His Arg Gln Lys Glu Gln Asp Val Glu Lys Glu Leu Arg 195 200 205 Asp Gly Gly Glu Gln Asp Thr Trp Ala Gly Glu Gly Ala Glu Ala Leu 210 215 220 Ala Arg Asn Leu Leu Val Asp Gly Glu Thr Gly Glu Ser Phe Pro Ala 225 230 235 240 Gln Val Pro Ser Gly Glu Asp Gln Thr Ala Leu Ser Leu Glu Glu Cys 245 250 255 Leu Arg Leu Leu Glu Ala Thr Cys Pro Phe Gly Glu Asn Ala Glu Phe 260 265 270 Pro Ala Asp Ile Ser Ser Ile Thr Glu Ala Val Pro Ser Glu Ser Glu 275 280 285 Pro Pro Ala Leu Gln Asn Asn Leu Leu Ser Pro Leu Leu Thr Gly Thr 290 295 300 Glu Ser Pro Phe Asp Leu Glu Gln Gln Trp Gln Asp Leu Met Ser Ile 305 310 315 320 Met Glu Met Gln Ala Met Glu Val Asn Thr Ser Ala Ser Glu Ile Leu 325 330 335 Tyr Ser Ala Pro Pro Gly Asp Pro Leu Ser Thr Asn Tyr Ser Leu Ala 340 345 350 Pro Asn Thr Pro Ile Asn Gln Asn Val Ser Leu His Gln Ala Ser Leu 355 360 365 Gly Gly Cys Ser Gln Asp Phe Leu Leu Phe Ser Pro Glu Val Glu Ser 370 375 380 Leu Pro Val Ala Ser Ser Ser Thr Leu Leu Pro Leu Ala Pro Ser Asn 385 390 395 400 Ser Thr Ser Leu Asn Ser Thr Phe Gly Ser Thr Asn Leu Thr Gly Leu 405 410 415 Phe Phe Pro Pro Gln Leu Asn Gly Thr Ala Asn Asp Thr Ala Gly Pro 420 425 430 Glu Leu Pro Asp Pro Leu Gly Gly Leu Leu Asp Glu Ala Met Leu Asp 435 440 445 Glu Ile Ser Leu Met Asp Leu Ala Ile Glu Glu Gly Phe Asn Pro Val 450 455 460 Gln Ala Ser Gln Leu Glu Glu Glu Phe Asp Ser Asp Ser Gly Leu Ser 465 470 475 480 Leu Asp Ser Ser His Ser Pro Ser Ser Leu Ser Ser Ser Glu Gly Ser 485 490 495 Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ala Ser Ser 500 505 510 Ser Ala Ser Ser Ser Phe Ser Glu Glu Gly Ala Val Gly Tyr Ser Ser 515 520 525 Asp Ser Glu Thr Leu Asp Leu Glu Glu Ala Glu Gly Ala Val Gly Tyr 530 535 540 Gln Pro Glu Tyr Ser Lys Phe Cys Arg Met Ser Tyr Gln Asp Pro Ala 545 550 555 560 Gln Leu Ser Cys Leu Pro Tyr Leu Glu His Val Gly His Asn His Thr 565 570 575 Tyr Asn Met Ala Pro Ser Ala Leu Asp Ser Ala Asp Leu Pro Pro Pro 580 585 590 Ser Ala Leu Lys Lys Gly Ser Lys Glu Lys Gln Ala Asp Phe Leu Asp 595 600 605 Lys Gln Met Ser Arg Asp Glu His Arg Ala Arg Ala Met Lys Ile Pro 610 615 620 Phe Thr Asn Asp Lys Ile Ile Asn Leu Pro Val Glu Glu Phe Asn Glu 625 630 635 640 Leu Leu Ser Lys Tyr Gln Leu Ser Glu Ala Gln Leu Ser Leu Ile Arg 645 650 655 Asp Ile Arg Arg Arg Gly Lys Asn Lys Met Ala Ala Gln Asn Cys Arg 660 665 670 Lys Arg Lys Leu Asp Thr Ile Leu Asn Leu Glu Arg Asp Val Glu Asp 675 680 685 Leu Gln Arg Asp Lys Ala Arg Leu Leu Arg Glu Lys Val Glu Phe Leu 690 695 700 Arg Ser Leu Arg Gln Met Lys Gln Lys Val Gln Ser Leu Tyr Gln Glu 705 710 715 720 Val Phe Gly Arg Leu Arg Asp Glu Asn Gly Arg Pro Tyr Ser Pro Ser 725 730 735 Gln Tyr Ala Leu Gln Tyr Ala Gly Asp Gly Ser Val Leu Leu Ile Pro 740 745 750 Arg Thr Met Ala Asp Gln Gln Ala Arg Arg Gln Glu Arg Lys Pro Lys 755 760 765 Asp Arg Arg Lys 770 <![CDATA[<210> 84]]> <![CDATA[<211> 152]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 84]]> Met Ala Asn Leu Glu Arg Thr Phe Ile Ala Ile Lys Pro Asp Gly Val 1 5 10 15 Gln Arg Gly Leu Val Gly Glu Ile Ile Lys Arg Phe Glu Gln Lys Gly 20 25 30 Phe Arg Leu Val Ala Met Lys Phe Leu Arg Ala Ser Glu Glu His Leu 35 40 45 Lys Gln His Tyr Ile Asp Leu Lys Asp Arg Pro Phe Phe Pro Gly Leu 50 55 60 Val Lys Tyr Met Asn Ser Gly Pro Val Val Ala Met Val Trp Glu Gly 65 70 75 80 Leu Asn Val Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn Pro 85 90 95 Ala Asp Ser Lys Pro Gly Thr Ile Arg Gly Asp Phe Cys Ile Gln Val 100 105 110 Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Lys Ser Ala Glu Lys 115 120 125 Glu Ile Ser Leu Trp Phe Lys Pro Glu Glu Leu Val Asp Tyr Lys Ser 130 135 140 Cys Ala His Asp Trp Val Tyr Glu 145 150 <![CDATA[<210> 85]]> <![CDATA[<211> 614]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 85]]> Met Thr Thr Leu Asp Ser Asn Asn Asn Thr Gly Gly Val Ile Thr Tyr 1 5 10 15 Ile Gly Ser Ser Gly Ser Ser Pro Ser Arg Thr Ser Pro Glu Ser Leu 20 25 30 Tyr Ser Asp Asn Ser Asn Gly Ser Phe Gln Ser Leu Thr Gln Gly Cys 35 40 45 Pro Thr Tyr Phe Pro Pro Ser Pro Thr Gly Ser Leu Thr Gln Asp Pro 50 55 60 Ala Arg Ser Phe Gly Ser Ile Pro Pro Ser Leu Ser Asp Asp Gly Ser 65 70 75 80 Pro Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Phe Tyr Asn 85 90 95 Gly Ser Pro Pro Gly Ser Leu Gln Val Ala Met Glu Asp Ser Ser Arg 100 105 110 Val Ser Pro Ser Lys Ser Thr Ser Asn Ile Thr Lys Leu Asn Gly Met 115 120 125 Val Leu Leu Cys Lys Val Cys Gly Asp Val Ala Ser Gly Phe His Tyr 130 135 140 Gly Val His Ala Cys Glu Gly Cys Lys Gly Phe Phe Arg Arg Ser Ile 145 150 155 160 Gln Gln Asn Ile Gln Tyr Lys Arg Cys Leu Lys Asn Glu Asn Cys Ser 165 170 175 Ile Val Arg Ile Asn Arg Asn Arg Cys Gln Gln Cys Arg Phe Lys Lys 180 185 190 Cys Leu Ser Val Gly Met Ser Arg Asp Ala Val Arg Phe Gly Arg Ile 195 200 205 Pro Lys Arg Glu Lys Gln Arg Met Leu Ala Glu Met Gln Ser Ala Met 210 215 220 Asn Leu Ala Asn Asn Gln Leu Ser Ser Gln Cys Pro Leu Glu Thr Ser 225 230 235 240 Pro Thr Gln His Pro Thr Pro Gly Pro Met Gly Pro Ser Pro Pro Pro 245 250 255 Ala Pro Val Pro Ser Pro Leu Val Gly Phe Ser Gln Phe Pro Gln Gln 260 265 270 Leu Thr Pro Pro Arg Ser Pro Ser Pro Glu Pro Thr Val Glu Asp Val 275 280 285 Ile Ser Gln Val Ala Arg Ala His Arg Glu Ile Phe Thr Tyr Ala His 290 295 300 Asp Lys Leu Gly Ser Ser Pro Gly Asn Phe Asn Ala Asn His Ala Ser 305 310 315 320 Gly Ser Pro Pro Ala Thr Thr Pro His Arg Trp Glu Asn Gln Gly Cys 325 330 335 Pro Pro Ala Pro Asn Asp Asn Asn Thr Leu Ala Ala Gln Arg His Asn 340 345 350 Glu Ala Leu Asn Gly Leu Arg Gln Ala Pro Ser Ser Tyr Pro Pro Thr 355 360 365 Trp Pro Pro Gly Pro Ala His His Ser Cys His Gln Ser Asn Ser Asn 370 375 380 Gly His Arg Leu Cys Pro Thr His Val Tyr Ala Ala Pro Glu Gly Lys 385 390 395 400 Ala Pro Ala Asn Ser Pro Arg Gln Gly Asn Ser Lys Asn Val Leu Leu 405 410 415 Ala Cys Pro Met Asn Met Tyr Pro His Gly Arg Ser Gly Arg Thr Val 420 425 430 Gln Glu Ile Trp Glu Asp Phe Ser Met Ser Phe Thr Pro Ala Val Arg 435 440 445 Glu Val Val Glu Phe Ala Lys His Ile Pro Gly Phe Arg Asp Leu Ser 450 455 460 Gln His Asp Gln Val Thr Leu Leu Lys Ala Gly Thr Phe Glu Val Leu 465 470 475 480 Met Val Arg Phe Ala Ser Leu Phe Asn Val Lys Asp Gln Thr Val Met 485 490 495 Phe Leu Ser Arg Thr Thr Tyr Ser Leu Gln Glu Leu Gly Ala Met Gly 500 505 510 Met Gly Asp Leu Leu Ser Ala Met Phe Asp Phe Ser Glu Lys Leu Asn 515 520 525 Ser Leu Ala Leu Thr Glu Glu Glu Leu Gly Leu Phe Thr Ala Val Val 530 535 540 Leu Val Ser Ala Asp Arg Ser Gly Met Glu Asn Ser Ala Ser Val Glu 545 550 555 560 Gln Leu Gln Glu Thr Leu Leu Arg Ala Leu Arg Ala Leu Val Leu Lys 565 570 575 Asn Arg Pro Leu Glu Thr Ser Arg Phe Thr Lys Leu Leu Leu Lys Leu 580 585 590 Pro Asp Leu Arg Thr Leu Asn Asn Met His Ser Glu Lys Leu Leu Ser 595 600 605 Phe Arg Val Asp Ala Gln 610 <![CDATA[<210> 86]]> <![CDATA[<211> 598]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 86]]> Met Pro Cys Ile Gln Ala Gln Tyr Gly Thr Pro Ala Pro Ser Pro Gly 1 5 10 15 Pro Arg Asp His Leu Ala Ser Asp Pro Leu Thr Pro Glu Phe Ile Lys 20 25 30 Pro Thr Met Asp Leu Ala Ser Pro Glu Ala Ala Pro Ala Ala Pro Thr 35 40 45 Ala Leu Pro Ser Phe Ser Thr Phe Met Asp Gly Tyr Thr Gly Glu Phe 50 55 60 Asp Thr Phe Leu Tyr Gln Leu Pro Gly Thr Val Gln Pro Cys Ser Ser 65 70 75 80 Ala Ser Ser Ser Ala Ser Ser Thr Ser Ser Ser Ser Ala Thr Ser Pro 85 90 95 Ala Ser Ala Ser Phe Lys Phe Glu Asp Phe Gln Val Tyr Gly Cys Tyr 100 105 110 Pro Gly Pro Leu Ser Gly Pro Val Asp Glu Ala Leu Ser Ser Ser Gly 115 120 125 Ser Asp Tyr Tyr Gly Ser Pro Cys Ser Ala Pro Ser Pro Ser Thr Pro 130 135 140 Ser Phe Gln Pro Pro Gln Leu Ser Pro Trp Asp Gly Ser Phe Gly His 145 150 155 160 Phe Ser Pro Ser Gln Thr Tyr Glu Gly Leu Arg Ala Trp Thr Glu Gln 165 170 175 Leu Pro Lys Ala Ser Gly Pro Pro Gln Pro Pro Ala Phe Phe Ser Phe 180 185 190 Ser Pro Pro Thr Gly Pro Ser Pro Ser Leu Ala Gln Ser Pro Leu Lys 195 200 205 Leu Phe Pro Ser Gln Ala Thr His Gln Leu Gly Glu Gly Glu Ser Tyr 210 215 220 Ser Met Pro Thr Ala Phe Pro Gly Leu Ala Pro Thr Ser Pro His Leu 225 230 235 240 Glu Gly Ser Gly Ile Leu Asp Thr Pro Val Thr Ser Thr Lys Ala Arg 245 250 255 Ser Gly Ala Pro Gly Gly Ser Glu Gly Arg Cys Ala Val Cys Gly Asp 260 265 270 Asn Ala Ser Cys Gln His Tyr Gly Val Arg Thr Cys Glu Gly Cys Lys 275 280 285 Gly Phe Phe Lys Arg Thr Val Gln Lys Asn Ala Lys Tyr Ile Cys Leu 290 295 300 Ala Asn Lys Asp Cys Pro Val Asp Lys Arg Arg Arg Asn Arg Cys Gln 305 310 315 320 Phe Cys Arg Phe Gln Lys Cys Leu Ala Val Gly Met Val Lys Glu Val 325 330 335 Val Arg Thr Asp Ser Leu Lys Gly Arg Arg Gly Arg Leu Pro Ser Lys 340 345 350 Pro Lys Gln Pro Pro Asp Ala Ser Pro Ala Asn Leu Leu Thr Ser Leu 355 360 365 Val Arg Ala His Leu Asp Ser Gly Pro Ser Thr Ala Lys Leu Asp Tyr 370 375 380 Ser Lys Phe Gln Glu Leu Val Leu Pro His Phe Gly Lys Glu Asp Ala 385 390 395 400 Gly Asp Val Gln Gln Phe Tyr Asp Leu Leu Ser Gly Ser Leu Glu Val 405 410 415 Ile Arg Lys Trp Ala Glu Lys Ile Pro Gly Phe Ala Glu Leu Ser Pro 420 425 430 Ala Asp Gln Asp Leu Leu Leu Glu Ser Ala Phe Leu Glu Leu Phe Ile 435 440 445 Leu Arg Leu Ala Tyr Arg Ser Lys Pro Gly Glu Gly Lys Leu Ile Phe 450 455 460 Cys Ser Gly Leu Val Leu His Arg Leu Gln Cys Ala Arg Gly Phe Gly 465 470 475 480 Asp Trp Ile Asp Ser Ile Leu Ala Phe Ser Arg Ser Leu His Ser Leu 485 490 495 Leu Val Asp Val Pro Ala Phe Ala Cys Leu Ser Ala Leu Val Leu Ile 500 505 510 Thr Asp Arg His Gly Leu Gln Glu Pro Arg Arg Val Glu Glu Leu Gln 515 520 525 Asn Arg Ile Ala Ser Cys Leu Lys Glu His Val Ala Ala Val Ala Gly 530 535 540 Glu Pro Gln Pro Ala Ser Cys Leu Ser Arg Leu Leu Gly Lys Leu Pro 545 550 555 560 Glu Leu Arg Thr Leu Cys Thr Gln Gly Leu Gln Arg Ile Phe Tyr Leu 565 570 575 Lys Leu Glu Asp Leu Val Pro Pro Pro Pro Ile Ile Asp Lys Ile Phe 580 585 590 Met Asp Thr Leu Pro Phe 595 <![CDATA[<210> 87]]> <![CDATA[<211> 394]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 87]]> Met Ser Gly Glu Asp Glu Gln Gln Glu Gln Thr Ile Ala Glu Asp Leu 1 5 10 15 Val Val Thr Lys Tyr Lys Met Gly Gly Asp Ile Ala Asn Arg Val Leu 20 25 30 Arg Ser Leu Val Glu Ala Ser Ser Ser Gly Val Ser Val Leu Ser Leu 35 40 45 Cys Glu Lys Gly Asp Ala Met Ile Met Glu Glu Thr Gly Lys Ile Phe 50 55 60 Lys Lys Glu Lys Glu Met Lys Lys Gly Ile Ala Phe Pro Thr Ser Ile 65 70 75 80 Ser Val Asn Asn Cys Val Cys His Phe Ser Pro Leu Lys Ser Asp Gln 85 90 95 Asp Tyr Ile Leu Lys Glu Gly Asp Leu Val Lys Ile Asp Leu Gly Val 100 105 110 His Val Asp Gly Phe Ile Ala Asn Val Ala His Thr Phe Val Val Asp 115 120 125 Val Ala Gln Gly Thr Gln Val Thr Gly Arg Lys Ala Asp Val Ile Lys 130 135 140 Ala Ala His Leu Cys Ala Glu Ala Ala Leu Arg Leu Val Lys Pro Gly 145 150 155 160 Asn Gln Asn Thr Gln Val Thr Glu Ala Trp Asn Lys Val Ala His Ser 165 170 175 Phe Asn Cys Thr Pro Ile Glu Gly Met Leu Ser His Gln Leu Lys Gln 180 185 190 His Val Ile Asp Gly Glu Lys Thr Ile Ile Gln Asn Pro Thr Asp Gln 195 200 205 Gln Lys Lys Asp His Glu Lys Ala Glu Phe Glu Val His Glu Val Tyr 210 215 220 Ala Val Asp Val Leu Val Ser Ser Gly Glu Gly Lys Ala Lys Asp Ala 225 230 235 240 Gly Gln Arg Thr Thr Ile Tyr Lys Arg Asp Pro Ser Lys Gln Tyr Gly 245 250 255 Leu Lys Met Lys Thr Ser Arg Ala Phe Phe Ser Glu Val Glu Arg Arg 260 265 270 Phe Asp Ala Met Pro Phe Thr Leu Arg Ala Phe Glu Asp Glu Lys Lys 275 280 285 Ala Arg Met Gly Val Val Glu Cys Ala Lys His Glu Leu Leu Gln Pro 290 295 300 Phe Asn Val Leu Tyr Glu Lys Glu Gly Glu Phe Val Ala Gln Phe Lys 305 310 315 320 Phe Thr Val Leu Leu Met Pro Asn Gly Pro Met Arg Ile Thr Ser Gly 325 330 335 Pro Phe Glu Pro Asp Leu Tyr Lys Ser Glu Met Glu Val Gln Asp Ala 340 345 350 Glu Leu Lys Ala Leu Leu Gln Ser Ser Ala Ser Arg Lys Thr Gln Lys 355 360 365 Lys Lys Lys Lys Lys Ala Ser Lys Thr Ala Glu Asn Ala Thr Ser Gly 370 375 380 Glu Thr Leu Glu Glu Asn Glu Ala Gly Asp 385 390 <![CDATA[<210> 88]]> <![CDATA[<211> 500]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 88]]> Met Ala Thr Ala Ala Ser Asn Pro Tyr Leu Pro Gly Asn Ser Leu Leu 1 5 10 15 Ala Ala Gly Ser Ile Val His Ser Asp Ala Ala Gly Ala Gly Gly Gly 20 25 30 Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Ala Gly Gly Gly Gly 35 40 45 Gly Gly Met Gln Pro Gly Ser Ala Ala Val Thr Ser Gly Ala Tyr Arg 50 55 60 Gly Asp Pro Ser Ser Val Lys Met Val Gln Ser Asp Phe Met Gln Gly 65 70 75 80 Ala Met Ala Ala Ser Asn Gly Gly His Met Leu Ser His Ala His Gln 85 90 95 Trp Val Thr Ala Leu Pro His Ala Ala Ala Ala Ala Ala Ala Ala Ala 100 105 110 Ala Ala Ala Val Glu Ala Ser Ser Pro Trp Ser Gly Ser Ala Val Gly 115 120 125 Met Ala Gly Ser Pro Gln Gln Pro Pro Gln Pro Pro Pro Pro Pro Pro 130 135 140 Gln Gly Pro Asp Val Lys Gly Gly Ala Gly Arg Asp Asp Leu His Ala 145 150 155 160 Gly Thr Ala Leu His His Arg Gly Pro Pro His Leu Gly Pro Pro Pro 165 170 175 Pro Pro Pro His Gln Gly His Pro Gly Gly Trp Gly Ala Ala Ala Ala 180 185 190 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala His Leu Pro Ser 195 200 205 Met Ala Gly Gly Gln Gln Pro Pro Pro Gln Ser Leu Leu Tyr Ser Gln 210 215 220 Pro Gly Gly Phe Thr Val Asn Gly Met Leu Ser Ala Pro Pro Gly Pro 225 230 235 240 Gly Gly Gly Gly Gly Gly Ala Gly Gly Gly Ala Gln Ser Leu Val His 245 250 255 Pro Gly Leu Val Arg Gly Asp Thr Pro Glu Leu Ala Glu His His His 260 265 270 His His His His His Ala His Pro His Pro Pro His Pro His His Ala 275 280 285 Gln Gly Pro Pro His His Gly Gly Gly Gly Gly Gly Ala Gly Pro Gly 290 295 300 Leu Asn Ser His Asp Pro His Ser Asp Glu Asp Thr Pro Thr Ser Asp 305 310 315 320 Asp Leu Glu Gln Phe Ala Lys Gln Phe Lys Gln Arg Arg Ile Lys Leu 325 330 335 Gly Phe Thr Gln Ala Asp Val Gly Leu Ala Leu Gly Thr Leu Tyr Gly 340 345 350 Asn Val Phe Ser Gln Thr Thr Ile Cys Arg Phe Glu Ala Leu Gln Leu 355 360 365 Ser Phe Lys Asn Met Cys Lys Leu Lys Pro Leu Leu Asn Lys Trp Leu 370 375 380 Glu Glu Ala Asp Ser Ser Thr Gly Ser Pro Thr Ser Ile Asp Lys Ile 385 390 395 400 Ala Ala Gln Gly Arg Lys Arg Lys Lys Arg Thr Ser Ile Glu Val Ser 405 410 415 Val Lys Gly Ala Leu Glu Ser His Phe Leu Lys Cys Pro Lys Pro Ser 420 425 430 Ala Gln Glu Ile Thr Asn Leu Ala Asp Ser Leu Gln Leu Glu Lys Glu 435 440 445 Val Val Arg Val Trp Phe Cys Asn Arg Arg Gln Lys Glu Lys Arg Met 450 455 460 Thr Pro Pro Gly Ile Gln Gln Gln Thr Pro Asp Asp Val Tyr Ser Gln 465 470 475 480 Val Gly Thr Val Ser Ala Asp Thr Pro Pro Pro His His Gly Leu Gln 485 490 495 Thr Ser Val Gln 500 <![CDATA[<210> 89]]> <![CDATA[<211> 551]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 89]]> Met Asp Glu Leu Phe Pro Leu Ile Phe Pro Ala Glu Pro Ala Gln Ala 1 5 10 15 Ser Gly Pro Tyr Val Glu Ile Ile Glu Gln Pro Lys Gln Arg Gly Met 20 25 30 Arg Phe Arg Tyr Lys Cys Glu Gly Arg Ser Ala Gly Ser Ile Pro Gly 35 40 45 Glu Arg Ser Thr Asp Thr Thr Lys Thr His Pro Thr Ile Lys Ile Asn 50 55 60 Gly Tyr Thr Gly Pro Gly Thr Val Arg Ile Ser Leu Val Thr Lys Asp 65 70 75 80 Pro Pro His Arg Pro His Pro His Glu Leu Val Gly Lys Asp Cys Arg 85 90 95 Asp Gly Phe Tyr Glu Ala Glu Leu Cys Pro Asp Arg Cys Ile His Ser 100 105 110 Phe Gln Asn Leu Gly Ile Gln Cys Val Lys Lys Arg Asp Leu Glu Gln 115 120 125 Ala Ile Ser Gln Arg Ile Gln Thr Asn Asn Asn Pro Phe Gln Val Pro 130 135 140 Ile Glu Glu Gln Arg Gly Asp Tyr Asp Leu Asn Ala Val Arg Leu Cys 145 150 155 160 Phe Gln Val Thr Val Arg Asp Pro Ser Gly Arg Pro Leu Arg Leu Pro 165 170 175 Pro Val Leu Ser His Pro Ile Phe Asp Asn Arg Ala Pro Asn Thr Ala 180 185 190 Glu Leu Lys Ile Cys Arg Val Asn Arg Asn Ser Gly Ser Cys Leu Gly 195 200 205 Gly Asp Glu Ile Phe Leu Leu Cys Asp Lys Val Gln Lys Glu Asp Ile 210 215 220 Glu Val Tyr Phe Thr Gly Pro Gly Trp Glu Ala Arg Gly Ser Phe Ser 225 230 235 240 Gln Ala Asp Val His Arg Gln Val Ala Ile Val Phe Arg Thr Pro Pro 245 250 255 Tyr Ala Asp Pro Ser Leu Gln Ala Pro Val Arg Val Ser Met Gln Leu 260 265 270 Arg Arg Pro Ser Asp Arg Glu Leu Ser Glu Pro Met Glu Phe Gln Tyr 275 280 285 Leu Pro Asp Thr Asp Asp Arg His Arg Ile Glu Glu Lys Arg Lys Arg 290 295 300 Thr Tyr Glu Thr Phe Lys Ser Ile Met Lys Lys Ser Pro Phe Ser Gly 305 310 315 320 Pro Thr Asp Pro Arg Pro Pro Pro Arg Arg Ile Ala Val Pro Ser Arg 325 330 335 Ser Ser Ala Ser Val Pro Lys Pro Ala Pro Gln Pro Tyr Pro Phe Thr 340 345 350 Ser Ser Leu Ser Thr Ile Asn Tyr Asp Glu Phe Pro Thr Met Val Phe 355 360 365 Pro Ser Gly Gln Ile Ser Gln Ala Ser Ala Leu Ala Pro Ala Pro Pro 370 375 380 Gln Val Leu Pro Gln Ala Pro Ala Pro Ala Pro Ala Pro Ala Met Val 385 390 395 400 Ser Ala Leu Ala Gln Ala Pro Ala Pro Val Pro Val Leu Ala Pro Gly 405 410 415 Pro Pro Gln Ala Val Ala Pro Pro Ala Pro Lys Pro Thr Gln Ala Gly 420 425 430 Glu Gly Thr Leu Ser Glu Ala Leu Leu Gln Leu Gln Phe Asp Asp Glu 435 440 445 Asp Leu Gly Ala Leu Leu Gly Asn Ser Thr Asp Pro Ala Val Phe Thr 450 455 460 Asp Leu Ala Ser Val Asp Asn Ser Glu Phe Gln Gln Leu Leu Asn Gln 465 470 475 480 Gly Ile Pro Val Ala Pro His Thr Thr Glu Pro Met Leu Met Glu Tyr 485 490 495 Pro Glu Ala Ile Thr Arg Leu Val Thr Gly Ala Gln Arg Pro Pro Asp 500 505 510 Pro Ala Pro Ala Pro Leu Gly Ala Pro Gly Leu Pro Asn Gly Leu Leu 515 520 525 Ser Gly Asp Glu Asp Phe Ser Ser Ile Ala Asp Met Asp Phe Ser Ala 530 535 540 Leu Leu Ser Gln Ile Ser Ser 545 550 <![CDATA[<210> 90]]> <![CDATA[<211> 712]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 90]]> Met Arg Glu Pro Ala Leu Ala Ala Ser Ala Met Ala Tyr His Pro Phe 1 5 10 15 His Ala Pro Arg Pro Ala Asp Phe Pro Met Ser Ala Phe Leu Ala Ala 20 25 30 Ala Gln Pro Ser Phe Phe Pro Ala Leu Ala Leu Pro Pro Gly Ala Leu 35 40 45 Ala Lys Pro Leu Pro Asp Pro Gly Leu Ala Gly Ala Ala Ala Ala Ala 50 55 60 Ala Ala Ala Ala Ala Ala Ala Glu Ala Gly Leu His Val Ser Ala Leu 65 70 75 80 Gly Pro His Pro Pro Ala Ala His Leu Arg Ser Leu Lys Ser Leu Glu 85 90 95 Pro Glu Asp Glu Val Glu Asp Asp Pro Lys Val Thr Leu Glu Ala Lys 100 105 110 Glu Leu Trp Asp Gln Phe His Lys Leu Gly Thr Glu Met Val Ile Thr 115 120 125 Lys Ser Gly Arg Arg Met Phe Pro Pro Phe Lys Val Arg Val Ser Gly 130 135 140 Leu Asp Lys Lys Ala Lys Tyr Ile Leu Leu Met Asp Ile Val Ala Ala 145 150 155 160 Asp Asp Cys Arg Tyr Lys Phe His Asn Ser Arg Trp Met Val Ala Gly 165 170 175 Lys Ala Asp Pro Glu Met Pro Lys Arg Met Tyr Ile His Pro Asp Ser 180 185 190 Pro Ala Thr Gly Glu Gln Trp Met Ala Lys Pro Val Ala Phe His Lys 195 200 205 Leu Lys Leu Thr Asn Asn Ile Ser Asp Lys His Gly Phe Thr Ile Leu 210 215 220 Asn Ser Met His Lys Tyr Gln Pro Arg Phe His Ile Val Arg Ala Asn 225 230 235 240 Asp Ile Leu Lys Leu Pro Tyr Ser Thr Phe Arg Thr Tyr Val Phe Pro 245 250 255 Glu Thr Asp Phe Ile Ala Val Thr Ala Tyr Gln Asn Asp Lys Ile Thr 260 265 270 Gln Leu Lys Ile Asp Asn Asn Pro Phe Ala Lys Gly Phe Arg Asp Thr 275 280 285 Gly Asn Gly Arg Arg Glu Lys Arg Lys Gln Leu Thr Leu Pro Ser Leu 290 295 300 Arg Leu Tyr Glu Glu His Cys Lys Pro Glu Arg Asp Gly Ala Glu Ser 305 310 315 320 Asp Ala Ser Ser Cys Asp Pro Pro Pro Ala Arg Glu Pro Pro Thr Ser 325 330 335 Pro Gly Ala Ala Pro Ser Pro Leu Arg Leu His Arg Ala Arg Ala Glu 340 345 350 Glu Lys Ser Cys Ala Ala Asp Ser Asp Pro Glu Pro Glu Arg Leu Ser 355 360 365 Glu Glu Arg Ala Gly Ala Pro Leu Gly Arg Ser Pro Ala Pro Asp Ser 370 375 380 Ala Ser Pro Thr Arg Leu Thr Glu Pro Glu Arg Ala Arg Glu Arg Arg 385 390 395 400 Ser Pro Glu Arg Gly Lys Glu Pro Ala Glu Ser Gly Gly Asp Gly Pro 405 410 415 Phe Gly Leu Arg Ser Leu Glu Lys Glu Arg Ala Glu Ala Arg Arg Lys 420 425 430 Asp Glu Gly Arg Lys Glu Ala Ala Glu Gly Lys Glu Gln Gly Leu Ala 435 440 445 Pro Leu Val Val Gln Thr Asp Ser Ala Ser Pro Leu Gly Ala Gly His 450 455 460 Leu Pro Gly Leu Ala Phe Ser Ser His Leu His Gly Gln Gln Phe Phe 465 470 475 480 Gly Pro Leu Gly Ala Gly Gln Pro Leu Phe Leu His Pro Gly Gln Phe 485 490 495 Thr Met Gly Pro Gly Ala Phe Ser Ala Met Gly Met Gly His Leu Leu 500 505 510 Ala Ser Val Ala Gly Gly Gly Asn Gly Gly Gly Gly Gly Pro Gly Thr 515 520 525 Ala Ala Gly Leu Asp Ala Gly Gly Leu Gly Pro Ala Ala Ser Ala Ala 530 535 540 Ser Thr Ala Ala Pro Phe Pro Phe His Leu Ser Gln His Met Leu Ala 545 550 555 560 Ser Gln Gly Ile Pro Met Pro Thr Phe Gly Gly Leu Phe Pro Tyr Pro 565 570 575 Tyr Thr Tyr Met Ala Ala Ala Ala Ala Ala Ala Ser Ala Leu Pro Ala 580 585 590 Thr Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Leu Ser Arg 595 600 605 Ser Pro Phe Leu Gly Ser Ala Arg Pro Arg Leu Arg Phe Ser Pro Tyr 610 615 620 Gln Ile Pro Val Thr Ile Pro Pro Ser Thr Ser Leu Leu Thr Thr Gly 625 630 635 640 Leu Ala Ser Glu Gly Ser Lys Ala Ala Gly Gly Asn Ser Arg Glu Pro 645 650 655 Ser Pro Leu Pro Glu Leu Ala Leu Arg Lys Val Gly Ala Pro Ser Arg 660 665 670 Gly Ala Leu Ser Pro Ser Gly Ser Ala Lys Glu Ala Ala Asn Glu Leu 675 680 685 Gln Ser Ile Gln Arg Leu Val Ser Gly Leu Glu Ser Gln Arg Ala Leu 690 695 700 Ser Pro Gly Arg Glu Ser Pro Lys 705 710 <![CDATA[<210> 91]]> <![CDATA[<211> 410]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 91]]> Met Ala Lys Asp Ala Gly Leu Ile Glu Ala Asn Gly Glu Leu Lys Val 1 5 10 15 Phe Ile Asp Gln Asn Leu Ser Pro Gly Lys Gly Val Val Ser Leu Val 20 25 30 Ala Val His Pro Ser Thr Val Asn Pro Leu Gly Lys Gln Leu Leu Pro 35 40 45 Lys Thr Phe Gly Gln Ser Asn Val Asn Ile Ala Gln Gln Val Val Ile 50 55 60 Gly Thr Pro Gln Arg Pro Ala Ala Ser Asn Thr Leu Val Val Gly Ser 65 70 75 80 Pro His Thr Pro Ser Thr His Phe Ala Ser Gln Asn Gln Pro Ser Asp 85 90 95 Ser Ser Pro Trp Ser Ala Gly Lys Arg Asn Arg Lys Gly Glu Lys Asn 100 105 110 Gly Lys Gly Leu Arg His Phe Ser Met Lys Val Cys Glu Lys Val Gln 115 120 125 Arg Lys Gly Thr Thr Ser Tyr Asn Glu Val Ala Asp Glu Leu Val Ala 130 135 140 Glu Phe Ser Ala Ala Asp Asn His Ile Leu Pro Asn Glu Ser Ala Tyr 145 150 155 160 Asp Gln Lys Asn Ile Arg Arg Arg Val Tyr Asp Ala Leu Asn Val Leu 165 170 175 Met Ala Met Asn Ile Ile Ser Lys Glu Lys Lys Glu Ile Lys Trp Ile 180 185 190 Gly Leu Pro Thr Asn Ser Ala Gln Glu Cys Gln Asn Leu Glu Val Glu 195 200 205 Arg Gln Arg Arg Leu Glu Arg Ile Lys Gln Lys Gln Ser Gln Leu Gln 210 215 220 Glu Leu Ile Leu Gln Gln Ile Ala Phe Lys Asn Leu Val Gln Arg Asn 225 230 235 240 Arg His Ala Glu Gln Gln Ala Ser Arg Pro Pro Pro Pro Asn Ser Val 245 250 255 Ile His Leu Pro Phe Ile Ile Val Asn Thr Ser Lys Lys Thr Val Ile 260 265 270 Asp Cys Ser Ile Ser Asn Asp Lys Phe Glu Tyr Leu Phe Asn Phe Asp 275 280 285 Asn Thr Phe Glu Ile His Asp Asp Ile Glu Val Leu Lys Arg Met Gly 290 295 300 Met Ala Cys Gly Leu Glu Ser Gly Ser Cys Ser Ala Glu Asp Leu Lys 305 310 315 320 Met Ala Arg Ser Leu Val Pro Lys Ala Leu Glu Pro Tyr Val Thr Glu 325 330 335 Met Ala Gln Gly Thr Val Gly Gly Val Phe Ile Thr Thr Ala Gly Ser 340 345 350 Thr Ser Asn Gly Thr Arg Phe Ser Ala Ser Asp Leu Thr Asn Gly Ala 355 360 365 Asp Gly Met Leu Ala Thr Ser Ser Asn Gly Ser Gln Tyr Ser Gly Ser 370 375 380 Arg Val Glu Thr Pro Val Ser Tyr Val Gly Glu Asp Asp Glu Glu Asp 385 390 395 400 Asp Asp Phe Asn Glu Asn Asp Glu Asp Asp 405 410 <![CDATA[<210> 92]]> <![CDATA[<211> 144]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 92]]> Met Lys Ser Gln Trp Cys Arg Pro Val Ala Met Asp Leu Gly Val Tyr 1 5 10 15 Gln Leu Arg His Phe Ser Ile Ser Phe Leu Ser Ser Leu Leu Gly Thr 20 25 30 Glu Asn Ala Ser Val Arg Leu Asp Asn Ser Ser Ser Gly Ala Ser Val 35 40 45 Val Ala Ile Asp Asn Lys Ile Glu Gln Ala Met Asp Leu Val Lys Ser 50 55 60 His Leu Met Tyr Ala Val Arg Glu Glu Val Glu Val Leu Lys Glu Gln 65 70 75 80 Ile Lys Glu Leu Ile Glu Lys Asn Ser Gln Leu Glu Gln Glu Asn Asn 85 90 95 Leu Leu Lys Thr Leu Ala Ser Pro Glu Gln Leu Ala Gln Phe Gln Ala 100 105 110 Gln Leu Gln Thr Gly Ser Pro Pro Ala Thr Thr Gln Pro Gln Gly Thr 115 120 125 Thr Gln Pro Pro Ala Gln Pro Ala Ser Gln Gly Ser Gly Pro Thr Ala 130 135 140 <![CDATA[<210> 93]]> <![CDATA[<211> 346]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 93]]> Met Asp Met Leu Asp Pro Gly Leu Asp Pro Ala Ala Ser Ala Thr Ala 1 5 10 15 Ala Ala Ala Ala Ser His Asp Lys Gly Pro Glu Ala Glu Glu Gly Val 20 25 30 Glu Leu Gln Glu Gly Gly Asp Gly Pro Gly Ala Glu Glu Gln Thr Ala 35 40 45 Val Ala Ile Thr Ser Val Gln Gln Ala Ala Phe Gly Asp His Asn Ile 50 55 60 Gln Tyr Gln Phe Arg Thr Glu Thr Asn Gly Gly Gln Val Thr Tyr Arg 65 70 75 80 Val Val Gln Val Thr Asp Gly Gln Leu Asp Gly Gln Gly Asp Thr Ala 85 90 95 Gly Ala Val Ser Val Val Ser Thr Ala Ala Phe Ala Gly Gly Gln Gln 100 105 110 Ala Val Thr Gln Val Gly Val Asp Gly Ala Ala Gln Arg Pro Gly Pro 115 120 125 Ala Ala Ala Ser Val Pro Pro Gly Pro Ala Ala Pro Phe Pro Leu Ala 130 135 140 Val Ile Gln Asn Pro Phe Ser Asn Gly Gly Ser Pro Ala Ala Glu Ala 145 150 155 160 Val Ser Gly Glu Ala Arg Phe Ala Tyr Phe Pro Ala Ser Ser Val Gly 165 170 175 Asp Thr Thr Ala Val Ser Val Gln Thr Thr Asp Gln Ser Leu Gln Ala 180 185 190 Gly Gly Gln Phe Tyr Val Met Met Thr Pro Gln Asp Val Leu Gln Thr 195 200 205 Gly Thr Gln Arg Thr Ile Ala Pro Arg Thr His Pro Tyr Ser Pro Lys 210 215 220 Ile Asp Gly Thr Arg Thr Pro Arg Asp Glu Arg Arg Arg Ala Gln His 225 230 235 240 Asn Glu Val Glu Arg Arg Arg Arg Asp Lys Ile Asn Asn Trp Ile Val 245 250 255 Gln Leu Ser Lys Ile Ile Pro Asp Cys Asn Ala Asp Asn Ser Lys Thr 260 265 270 Gly Ala Ser Lys Gly Gly Ile Leu Ser Lys Ala Cys Asp Tyr Ile Arg 275 280 285 Glu Leu Arg Gln Thr Asn Gln Arg Met Gln Glu Thr Phe Lys Glu Ala 290 295 300 Glu Arg Leu Gln Met Asp Asn Glu Leu Leu Arg Gln Gln Ile Glu Glu 305 310 315 320 Leu Lys Asn Glu Asn Ala Leu Leu Arg Ala Gln Leu Gln Gln His Asn 325 330 335 Leu Glu Met Val Gly Glu Gly Thr Arg Gln 340 345 <![CDATA[<210> 94]]> <![CDATA[<211> 324]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 94]]> Met Ser Ser Glu Ala Glu Thr Gln Gln Pro Pro Ala Ala Pro Pro Ala 1 5 10 15 Ala Pro Ala Leu Ser Ala Ala Asp Thr Lys Pro Gly Thr Thr Gly Ser 20 25 30 Gly Ala Gly Ser Gly Gly Pro Gly Gly Leu Thr Ser Ala Ala Pro Ala 35 40 45 Gly Gly Asp Lys Lys Val Ile Ala Thr Lys Val Leu Gly Thr Val Lys 50 55 60 Trp Phe Asn Val Arg Asn Gly Tyr Gly Phe Ile Asn Arg Asn Asp Thr 65 70 75 80 Lys Glu Asp Val Phe Val His Gln Thr Ala Ile Lys Lys Asn Asn Pro 85 90 95 Arg Lys Tyr Leu Arg Ser Val Gly Asp Gly Glu Thr Val Glu Phe Asp 100 105 110 Val Val Glu Gly Glu Lys Gly Ala Glu Ala Ala Asn Val Thr Gly Pro 115 120 125 Gly Gly Val Pro Val Gln Gly Ser Lys Tyr Ala Ala Asp Arg Asn His 130 135 140 Tyr Arg Arg Tyr Pro Arg Arg Arg Gly Pro Pro Arg Asn Tyr Gln Gln 145 150 155 160 Asn Tyr Gln Asn Ser Glu Ser Gly Glu Lys Asn Glu Gly Ser Glu Ser 165 170 175 Ala Pro Glu Gly Gln Ala Gln Gln Arg Arg Pro Tyr Arg Arg Arg Arg 180 185 190 Phe Pro Pro Tyr Tyr Met Arg Arg Pro Tyr Gly Arg Arg Pro Gln Tyr 195 200 205 Ser Asn Pro Pro Val Gln Gly Glu Val Met Glu Gly Ala Asp Asn Gln 210 215 220 Gly Ala Gly Glu Gln Gly Arg Pro Val Arg Gln Asn Met Tyr Arg Gly 225 230 235 240 Tyr Arg Pro Arg Phe Arg Arg Gly Pro Pro Arg Gln Arg Gln Pro Arg 245 250 255 Glu Asp Gly Asn Glu Glu Asp Lys Glu Asn Gln Gly Asp Glu Thr Gln 260 265 270 Gly Gln Gln Pro Pro Gln Arg Arg Tyr Arg Arg Asn Phe Asn Tyr Arg 275 280 285 Arg Arg Arg Pro Glu Asn Pro Lys Pro Gln Asp Gly Lys Glu Thr Lys 290 295 300 Ala Ala Asp Pro Pro Ala Glu Asn Ser Ser Ala Pro Glu Ala Glu Gln 305 310 315 320 Gly Gly Ala Glu <![CDATA[<210> 95]]> <![CDATA[<211> 494]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 95]]> Met Gly Arg Lys Lys Lys Lys Gln Leu Lys Pro Trp Cys Trp Tyr Cys 1 5 10 15 Asn Arg Asp Phe Asp Asp Glu Lys Ile Leu Ile Gln His Gln Lys Ala 20 25 30 Lys His Phe Lys Cys His Ile Cys His Lys Lys Leu Tyr Thr Gly Pro 35 40 45 Gly Leu Ala Ile His Cys Met Gln Val His Lys Glu Thr Ile Asp Ala 50 55 60 Val Pro Asn Ala Ile Pro Gly Arg Thr Asp Ile Glu Leu Glu Ile Tyr 65 70 75 80 Gly Met Glu Gly Ile Pro Glu Lys Asp Met Asp Glu Arg Arg Arg Leu 85 90 95 Leu Glu Gln Lys Thr Gln Glu Ser Gln Lys Lys Lys Gln Gln Asp Asp 100 105 110 Ser Asp Glu Tyr Asp Asp Asp Asp Ser Ala Ala Ser Thr Ser Phe Gln 115 120 125 Pro Gln Pro Val Gln Pro Gln Gln Gly Tyr Ile Pro Pro Met Ala Gln 130 135 140 Pro Gly Leu Pro Pro Val Pro Gly Ala Pro Gly Met Pro Pro Gly Ile 145 150 155 160 Pro Pro Leu Met Pro Gly Val Pro Pro Leu Met Pro Gly Met Pro Pro 165 170 175 Val Met Pro Gly Met Pro Pro Gly Leu His His Gln Arg Lys Tyr Thr 180 185 190 Gln Ser Phe Cys Gly Glu Asn Ile Met Met Pro Met Gly Gly Met Met 195 200 205 Pro Pro Gly Pro Gly Ile Pro Pro Leu Met Pro Gly Met Pro Pro Gly 210 215 220 Met Pro Pro Pro Val Pro Arg Pro Gly Ile Pro Pro Met Thr Gln Ala 225 230 235 240 Gln Ala Val Ser Ala Pro Gly Ile Leu Asn Arg Pro Pro Ala Pro Thr 245 250 255 Ala Thr Val Pro Ala Pro Gln Pro Pro Val Thr Lys Pro Leu Phe Pro 260 265 270 Ser Ala Gly Gln Met Gly Thr Pro Val Thr Ser Ser Ser Thr Ala Ser 275 280 285 Ser Asn Ser Glu Ser Leu Ser Ala Ser Ser Lys Ala Leu Phe Pro Ser 290 295 300 Thr Ala Gln Ala Gln Ala Ala Val Gln Gly Pro Val Gly Thr Asp Phe 305 310 315 320 Lys Pro Leu Asn Ser Thr Pro Ala Thr Thr Thr Glu Pro Pro Lys Pro 325 330 335 Thr Phe Pro Ala Tyr Thr Gln Ser Thr Ala Ser Thr Thr Ser Thr Thr 340 345 350 Asn Ser Thr Ala Ala Lys Pro Ala Ala Ser Ile Thr Ser Lys Pro Ala 355 360 365 Thr Leu Thr Thr Thr Ser Ala Thr Ser Lys Leu Ile His Pro Asp Glu 370 375 380 Asp Ile Ser Leu Glu Glu Arg Arg Ala Gln Leu Pro Lys Tyr Gln Arg 385 390 395 400 Asn Leu Pro Arg Pro Gly Gln Ala Pro Ile Gly Asn Pro Pro Val Gly 405 410 415 Pro Ile Gly Gly Met Met Pro Pro Gln Pro Gly Ile Pro Gln Gln Gln 420 425 430 Gly Met Arg Pro Pro Met Pro Pro His Gly Gln Tyr Gly Gly His His 435 440 445 Gln Gly Met Pro Gly Tyr Leu Pro Gly Ala Met Pro Pro Tyr Gly Gln 450 455 460 Gly Pro Pro Met Val Pro Pro Tyr Gln Gly Gly Pro Pro Arg Pro Pro 465 470 475 480 Met Gly Met Arg Pro Pro Val Met Ser Gln Gly Gly Arg Tyr 485 490 <![CDATA[<210> 96]]> <![CDATA[<211> 568]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 96]]> Met Arg Arg Ser Val Leu Val Arg Asn Pro Gly His Lys Gly Leu Arg 1 5 10 15 Pro Val Tyr Glu Glu Leu Asp Ser Asp Ser Glu Asp Leu Asp Pro Asn 20 25 30 Pro Glu Asp Leu Asp Pro Val Ser Glu Asp Pro Glu Pro Asp Pro Glu 35 40 45 Asp Leu Asn Thr Val Pro Glu Asp Val Asp Pro Ser Tyr Glu Asp Leu 50 55 60 Glu Pro Val Ser Glu Asp Leu Asp Pro Asp Ala Glu Ala Pro Gly Ser 65 70 75 80 Glu Pro Gln Asp Pro Asp Pro Met Ser Ser Ser Phe Asp Leu Asp Pro 85 90 95 Asp Val Ile Gly Pro Val Pro Leu Ile Leu Asp Pro Asn Ser Asp Thr 100 105 110 Leu Ser Pro Gly Asp Pro Lys Val Asp Pro Ile Ser Ser Gly Leu Thr 115 120 125 Ala Thr Pro Gln Val Leu Ala Thr Ser Pro Ala Val Leu Pro Ala Pro 130 135 140 Ala Ser Pro Pro Arg Pro Phe Ser Cys Pro Asp Cys Gly Arg Ala Phe 145 150 155 160 Arg Arg Ser Ser Gly Leu Ser Gln His Arg Arg Thr His Ser Gly Glu 165 170 175 Lys Pro Tyr Arg Cys Pro Asp Cys Gly Lys Ser Phe Ser His Gly Ala 180 185 190 Thr Leu Ala Gln His Arg Gly Ile His Thr Gly Ala Arg Pro Tyr Gln 195 200 205 Cys Ala Ala Cys Gly Lys Ala Phe Gly Trp Arg Ser Thr Leu Leu Lys 210 215 220 His Arg Ser Ser His Ser Gly Glu Lys Pro His His Cys Pro Val Cys 225 230 235 240 Gly Lys Ala Phe Gly His Gly Ser Leu Leu Ala Gln His Leu Arg Thr 245 250 255 His Gly Gly Pro Arg Pro His Lys Cys Pro Val Cys Ala Lys Gly Phe 260 265 270 Gly Gln Gly Ser Ala Leu Leu Lys His Leu Arg Thr His Thr Gly Glu 275 280 285 Arg Pro Tyr Pro Cys Pro Gln Cys Gly Lys Ala Phe Gly Gln Ser Ser 290 295 300 Ala Leu Leu Gln His Gln Arg Thr His Thr Ala Glu Arg Pro Tyr Arg 305 310 315 320 Cys Pro His Cys Gly Lys Ala Phe Gly Gln Ser Ser Asn Leu Gln His 325 330 335 His Leu Arg Ile His Thr Gly Glu Arg Pro Tyr Ala Cys Pro His Cys 340 345 350 Ser Lys Ala Phe Gly Gln Ser Ser Ala Leu Leu Gln His Leu His Val 355 360 365 His Ser Gly Glu Arg Pro Tyr Arg Cys Gln Leu Cys Gly Lys Ala Phe 370 375 380 Gly Gln Ala Ser Ser Leu Thr Lys His Lys Arg Val His Glu Gly Ala 385 390 395 400 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 405 410 415 Gly Leu Gly Leu Gly Pro Gly Leu Ser Pro Ala Ser Met Met Arg Pro 420 425 430 Gly Gln Val Ser Leu Leu Gly Pro Asp Ala Val Ser Val Leu Gly Ser 435 440 445 Gly Leu Gly Leu Ser Pro Gly Thr Ser Ser Gly Arg Asn Pro Asp Pro 450 455 460 Gly Ser Gly Pro Gly Thr Leu Pro Asp Pro Ser Ser Lys Pro Leu Pro 465 470 475 480 Gly Ser Arg Ser Thr Pro Ser Pro Thr Pro Val Glu Ser Ser Asp Pro 485 490 495 Lys Ala Gly His Asp Ala Gly Pro Asp Leu Val Pro Ser Pro Asp Leu 500 505 510 Asp Pro Val Pro Ser Pro Asp Pro Asp Pro Val Pro Ser Pro Asp Pro 515 520 525 Asn Pro Val Ser Cys Pro Asp Pro Cys Ser Pro Thr Arg Gly Thr Val 530 535 540 Ser Pro Ala Leu Pro Thr Gly Glu Ser Pro Glu Trp Val Gln Glu Gln 545 550 555 560 Gly Ala Leu Leu Gly Pro Asp Gly 565 <![CDATA[<210> 97]]> <![CDATA[<211> 513]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 97]]> Met Ala Ser Val Leu Ser Arg Arg Leu Gly Lys Arg Ser Leu Leu Gly 1 5 10 15 Ala Arg Val Leu Gly Pro Ser Ala Ser Glu Gly Pro Ser Ala Ala Pro 20 25 30 Pro Ser Glu Pro Leu Leu Glu Gly Ala Ala Pro Gln Pro Phe Thr Thr 35 40 45 Ser Asp Asp Thr Pro Cys Gln Glu Gln Pro Lys Glu Val Leu Lys Ala 50 55 60 Pro Ser Thr Ser Gly Leu Gln Gln Val Ala Phe Gln Pro Gly Gln Lys 65 70 75 80 Val Tyr Val Trp Tyr Gly Gly Gln Glu Cys Thr Gly Leu Val Glu Gln 85 90 95 His Ser Trp Met Glu Gly Gln Val Thr Val Trp Leu Leu Glu Gln Lys 100 105 110 Leu Gln Val Cys Cys Arg Val Glu Glu Val Trp Leu Ala Glu Leu Gln 115 120 125 Gly Pro Cys Pro Gln Ala Pro Pro Leu Glu Pro Gly Ala Gln Ala Leu 130 135 140 Ala Tyr Arg Pro Val Ser Arg Asn Ile Asp Val Pro Lys Arg Lys Ser 145 150 155 160 Asp Ala Val Glu Met Asp Glu Met Met Ala Ala Met Val Leu Thr Ser 165 170 175 Leu Ser Cys Ser Pro Val Val Gln Ser Pro Pro Gly Thr Glu Ala Asn 180 185 190 Phe Ser Ala Ser Arg Ala Ala Cys Asp Pro Trp Lys Glu Ser Gly Asp 195 200 205 Ile Ser Asp Ser Gly Ser Ser Thr Thr Ser Gly His Trp Ser Gly Ser 210 215 220 Ser Gly Val Ser Thr Pro Ser Pro Pro His Pro Gln Ala Ser Pro Lys 225 230 235 240 Tyr Leu Gly Asp Ala Phe Gly Ser Pro Gln Thr Asp His Gly Phe Glu 245 250 255 Thr Asp Pro Asp Pro Phe Leu Leu Asp Glu Pro Ala Pro Arg Lys Arg 260 265 270 Lys Asn Ser Val Lys Val Met Tyr Lys Cys Leu Trp Pro Asn Cys Gly 275 280 285 Lys Val Leu Arg Ser Ile Val Gly Ile Lys Arg His Val Lys Ala Leu 290 295 300 His Leu Gly Asp Thr Val Asp Ser Asp Gln Phe Lys Arg Glu Glu Asp 305 310 315 320 Phe Tyr Tyr Thr Glu Val Gln Leu Lys Glu Glu Ser Ala Ala Ala Ala 325 330 335 Ala Ala Ala Ala Ala Gly Thr Pro Val Pro Gly Thr Pro Thr Ser Glu 340 345 350 Pro Ala Pro Thr Pro Ser Met Thr Gly Leu Pro Leu Ser Ala Leu Pro 355 360 365 Pro Pro Leu His Lys Ala Gln Ser Ser Gly Pro Glu His Pro Gly Pro 370 375 380 Glu Ser Ser Leu Pro Ser Gly Ala Leu Ser Lys Ser Ala Pro Gly Ser 385 390 395 400 Phe Trp His Ile Gln Ala Asp His Ala Tyr Gln Ala Leu Pro Ser Phe 405 410 415 Gln Ile Pro Val Ser Pro His Ile Tyr Thr Ser Val Ser Trp Ala Ala 420 425 430 Ala Pro Ser Ala Ala Cys Ser Leu Ser Pro Val Arg Ser Arg Ser Leu 435 440 445 Ser Phe Ser Glu Pro Gln Gln Pro Ala Pro Ala Met Lys Ser His Leu 450 455 460 Ile Val Thr Ser Pro Pro Arg Ala Gln Ser Gly Ala Arg Lys Ala Arg 465 470 475 480 Gly Glu Ala Lys Lys Cys Arg Lys Val Tyr Gly Ile Glu His Arg Asp 485 490 495 Gln Trp Cys Thr Ala Cys Arg Trp Lys Lys Ala Cys Gln Arg Phe Leu 500 505 510 Asp <![CDATA[<210> 98]]> <![CDATA[<211> 3046]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 98]]> agaagcgccg gagcgccgcg tgaggagccc ggccgtgagt gcgcgagtgt gccatggccg 60 cggccaccag gcgcgtgttc catctgcagc cgtgcgaaaa ctctcccacc atgtcgcaga 120 atggatactt cgaggattca agctactaca agtgtgacac agatgacacc ttcgaagccc 180 gagaggagat cctgggggat gaggccttcg acactgccaa ctcctccatc gtgtctggcg 240 agagtatccg tttttttgtc aatgtcaacc ttgagatgca ggccaccaac actgagaatg 300 aagcgacttc cggtggctgt gtgctcctgc acacctcccg aaagtacctg aagttaaaga 360 acttcaagga agagatccgt gcgcaccgcg acctagatgg cttcctggcg caggccagca 420 tcgtcctgaa cgagacggcc acctccctgg ataacgtgct gcggaccatg cttcgccgct 480 tcgccaggga ccctgacaac aatgagccca actgcaacct ggacctgctc atggccatgc 540 tcttcaccga tgccggggca cccatgcggg gtaaagtcca cctgctgtca gataccatcc 600 aaggggtcac cgccacagtg acaggggtgc ggtaccagca gtcgtggctc tgcatcatct 660 gtaccatgaa ggccctacag aagcggcacg tgtgcatcag ccgcctggtt cgcccacaga 720 actgggggga gaattcctgt gaggttcggt tcgtcatcct ggtgctggcc ccacccaaga 780 tgaaaagcac taagactgcg atggaggtgg cgcgcacgtt tgccaccatg ttctcggata 840 tcgccttccg ccagaagctc ctggagaccc gcacagagga ggaattcaag gaggccttgg 900 tgcatcagag acagctgctc accatggtga gccacggtcc agtggcgccg agaacgaagg 960 aacgcagcac agtctccctc cctgcccaca gacacccaga gcccccaaag tgcaaggact 1020 ttgtcccttt tgggaagggc atccgggagg acatcgcacg caggttcccc ttgtacccct 1080 tggacttcac tgatggcatt attgggaaaa acaaggctgt gggcaaatac atcaccacca 1140 ccctgttcct ctacttcgcc tgcctcctgc ccaccatcgc tttcgggtct ctcaatgacg 1200 agaacacaga cggggccatc gacgtgcaga agaccatagc cgggcagagc atcgggggcc 1260 tgctctacgc gctcttctct gggcagccat tggtgattct gctgaccacc gcgcccctgg 1320 cgctctacat ccaggtgatt cgtgtcatct gtgatgacta tgacctggac ttcaactcct 1380 tctacgcatg gacgggcctg tggaatagtt tcttccttgc gctttatgcc tttttcaacc 1440 tcagcctggt catgagtctc ttcaagaggt cgacggagga gatcatcgcc ctcttcattt 1500 ccatcacgtt tgtgctggat gccgtcaagg gcacggttaa aatcttctgg aagtactact 1560 atgggcatta cttggacgac tatcacacaa aaaggacttc atcccttgtc agcctgtcag 1620 gcctcggcgc cagcctcaac gccagcctcc acactgccct caacgccagc ttcctcgcca 1680 gccccacgga gctgccctcg gccacacact caggccaggc gaccgccgtg ctcagcctcc 1740 tcatcatgct gggcacgctc tggctgggct acaccctcta ccaattcaag aagagcccct 1800 acctgcaccc ctgcgtgcga gagatcctgt ccgactgcgc cctgcccatc gcggtgctcg 1860 ccttctccct catcagctcc catggcttcc gggaaatcga gatgagcaag ttccgctaca 1920 accccagcga gagccccttt gcgatggcgc agatccagtc gctgtccctg agggccgtca 1980 gcggtgccat gggcctcggc ttcctgctgt ccatgctctt cttcatcgag cagaacttgg 2040 tggccgcctt ggtgaatgca ccggagaaca ggctggtgaa gggcactgcc taccactggg 2100 acctcctgct cctcgccatc atcaacacag ggctgtctct gtttgggctg ccttggatcc 2160 atgccgccta cccccactcc ccgctgcacg tgcgagccct ggccttagtg gaggagcgtg 2220 tggagaacgg acacatctat gacacgattg tgaacgtgaa ggagacgcgg ctgacctcgc 2280 tgggcgccag cgtcctggtg ggcctgtccc tgttgctgct gccggtcccg cttcagtgga 2340 tccccaagcc cgtgctctat ggcctcttcc tctacatcgc gctcacctcc ctcgatggca 2400 accagctcgt ccagcgcgtg gccctgctgc tcaaggagca gactgcgtac cccccgacac 2460 actacatccg gagggtgccc cagaggaaga tccactactt cacgggcctg caggtgcttc 2520 agctgctgct gctgtgtgcc ttcggcatga gctccctgcc ctacatgaag atgatctttc 2580 ccctcatcat gatcgccatg atccccatcc gctatatcct gctgccccga atcattgaag 2640 ccaagtactt ggatgtcatg gacgctgagc acaggccttg actggcagac cctgcccacg 2700 ccccattcgc cagccctcca cgtcctccca ggctggctct ggagctgtga ggggaggtgt 2760 aggtgtgtgg gtgactgctc tgtgctgcgc cttctcatgg ctgactcagg cctggggcat 2820 ctgggcattg taggggtgca gtggtatgtg cccacccctc tcccattatc ctttagcttt 2880 aggccaagag cgttgctcag ggcagcttct gcccagggtg ggtgggactg agcaggatgg 2940 attttctttt gataaaagag tcgatgcctg aaagagaaac catttccttg attgtgtaag 3000 gaacttgctg gacgcacatt agagaataaa gctcctgttt ctaggc 3046 <![CDATA[<210> 99]]> <![CDATA[<211> 3089]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 99]]> ctttctccct agggtggcgt gggttgcatc cctcggaaga gcgaaggaat gagccaggtc 60 ggggggcggg gagacaggtg cacacaggag gtccagggct tggtccatgg ggctggtgac 120 ctttctgctt cccttgcaga aaactctccc accatgtcgc agaatggata cttcgaggat 180 tcaagctact acaagtgtga cacagatgac accttcgaag cccgagagga gatcctgggg 240 gatgaggcct tcgacactgc caactcctcc atcgtgtctg gcgagagtat ccgttttttt 300 gtcaatgtca accttgagat gcaggccacc aacactgaga atgaagcgac ttccggtggc 360 tgtgtgctcc tgcacacctc ccgaaagtac ctgaagttaa agaacttcaa ggaagagatc 420 cgtgcgcacc gcgacctaga tggcttcctg gcgcaggcca gcatcgtcct gaacgagacg 480 gccacctccc tggataacgt gctgcggacc atgcttcgcc gcttcgccag ggaccctgac 540 aacaatgagc ccaactgcaa cctggacctg ctcatggcca tgctcttcac cgatgccggg 600 gcacccatgc ggggtaaagt ccacctgctg tcagatacca tccaaggggt caccgccaca 660 gtgacagggg tgcggtacca gcagtcgtgg ctctgcatca tctgtaccat gaaggcccta 720 cagaagcggc acgtgtgcat cagccgcctg gttcgcccac agaactgggg ggagaattcc 780 tgtgaggttc ggttcgtcat cctggtgctg gccccaccca agatgaaaag cactaagact 840 gcgatggagg tggcgcgcac gtttgccacc atgttctcgg atatcgcctt ccgccagaag 900 ctcctggaga cccgcacaga ggaggaattc aaggaggcct tggtgcatca gagacagctg 960 ctcaccatgg tgagccacgg tccagtggcg ccgagaacga aggaacgcag cacagtctcc 1020 ctccctgccc acagacaccc agagccccca aagtgcaagg actttgtccc ttttgggaag 1080 ggcatccggg aggacatcgc acgcaggttc cccttgtacc ccttggactt cactgatggc 1140 attattggga aaaacaaggc tgtgggcaaa tacatcacca ccaccctgtt cctctacttc 1200 gcctgcctcc tgcccaccat cgctttcggg tctctcaatg acgagaacac agacggggcc 1260 atcgacgtgc agaagaccat agccgggcag agcatcgggg gcctgctcta cgcgctcttc 1320 tctgggcagc cattggtgat tctgctgacc accgcgcccc tggcgctcta catccaggtg 1380 attcgtgtca tctgtgatga ctatgacctg gacttcaact ccttctacgc atggacgggc 1440 ctgtggaata gtttcttcct tgcgctttat gcctttttca acctcagcct ggtcatgagt 1500 ctcttcaaga ggtcgacgga ggagatcatc gccctcttca tttccatcac gtttgtgctg 1560 gatgccgtca agggcacggt taaaatcttc tggaagtact actatgggca ttacttggac 1620 gactatcaca caaaaaggac ttcatccctt gtcagcctgt caggcctcgg cgccagcctc 1680 aacgccagcc tccacactgc cctcaacgcc agcttcctcg ccagccccac ggagctgccc 1740 tcggccacac actcaggcca ggcgaccgcc gtgctcagcc tcctcatcat gctgggcacg 1800 ctctggctgg gctacaccct ctaccaattc aagaagagcc cctacctgca cccctgcgtg 1860 cgagagatcc tgtccgactg cgccctgccc atcgcggtgc tcgccttctc cctcatcagc 1920 tcccatggct tccgggaaat cgagatgagc aagttccgct acaaccccag cgagagcccc 1980 tttgcgatgg cgcagatcca gtcgctgtcc ctgagggccg tcagcggtgc catgggcctc 2040 ggcttcctgc tgtccatgct cttcttcatc gagcagaact tggtggccgc cttggtgaat 2100 gcaccggaga acaggctggt gaagggcact gcctaccact gggacctcct gctcctcgcc 2160 atcatcaaca cagggctgtc tctgtttggg ctgccttgga tccatgccgc ctacccccac 2220 tccccgctgc acgtgcgagc cctggcctta gtggaggagc gtgtggagaa cggacacatc 2280 tatgacacga ttgtgaacgt gaaggagacg cggctgacct cgctgggcgc cagcgtcctg 2340 gtgggcctgt ccctgttgct gctgccggtc ccgcttcagt ggatccccaa gcccgtgctc 2400 tatggcctct tcctctacat cgcgctcacc tccctcgatg gcaaccagct cgtccagcgc 2460 gtggccctgc tgctcaagga gcagactgcg taccccccga cacactacat ccggagggtg 2520 ccccagagga agatccacta cttcacgggc ctgcaggtgc ttcagctgct gctgctgtgt 2580 gccttcggca tgagctccct gccctacatg aagatgatct ttcccctcat catgatcgcc 2640 atgatcccca tccgctatat cctgctgccc cgaatcattg aagccaagta cttggatgtc 2700 atggacgctg agcacaggcc ttgactggca gaccctgccc acgccccatt cgccagccct 2760 ccacgtcctc ccaggctggc tctggagctg tgaggggagg tgtaggtgtg tgggtgactg 2820 ctctgtgctg cgccttctca tggctgactc aggcctgggg catctgggca ttgtaggggt 2880 gcagtggtat gtgcccaccc ctctcccatt atcctttagc tttaggccaa gagcgttgct 2940 cagggcagct tctgcccagg gtgggtggga ctgagcagga tggattttct tttgataaaa 3000 gagtcgatgc ctgaaagaga aaccatttcc ttgattgtgt aaggaacttg ctggacgcac 3060 attagagaat aaagctcctg tttctaggc 3089 <![CDATA[<210> 100]]> <![CDATA[<211> 3245]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 100]]> cttttggacc aacggctctg gcttccaggc ggccgggacg cggtcccagg actggagacc 60 gttgcctgtc ggcccccgtg tgacccgggg cgcgtgacgg gggtcggggg aactgcgcct 120 gcaatgggcg tttatggccc ccaggaccgg tctgagagtg agaagaggga tgtgcagaga 180 gatcccccgc cttggcatcc gaggagagag ggggagaggc ccgctcgggc ccggtccctt 240 cctctcgctg cagcggggca gggttttctc aggaaaacct ggattagcga acatgaaaac 300 tctcccacca tgtcgcagaa tggatacttc gaggattcaa gctactacaa gtgtgacaca 360 gatgacacct tcgaagcccg agaggagatc ctgggggatg aggccttcga cactgccaac 420 tcctccatcg tgtctggcga gagtatccgt ttttttgtca atgtcaacct tgagatgcag 480 gccaccaaca ctgagaatga agcgacttcc ggtggctgtg tgctcctgca cacctcccga 540 aagtacctga agttaaagaa cttcaaggaa gagatccgtg cgcaccgcga cctagatggc 600 ttcctggcgc aggccagcat cgtcctgaac gagacggcca cctccctgga taacgtgctg 660 cggaccatgc ttcgccgctt cgccagggac cctgacaaca atgagcccaa ctgcaacctg 720 gacctgctca tggccatgct cttcaccgat gccggggcac ccatgcgggg taaagtccac 780 ctgctgtcag ataccatcca aggggtcacc gccacagtga caggggtgcg gtaccagcag 840 tcgtggctct gcatcatctg taccatgaag gccctacaga agcggcacgt gtgcatcagc 900 cgcctggttc gcccacagaa ctggggggag aattcctgtg aggttcggtt cgtcatcctg 960 gtgctggccc cacccaagat gaaaagcact aagactgcga tggaggtggc gcgcacgttt 1020 gccaccatgt tctcggatat cgccttccgc cagaagctcc tggagacccg cacagaggag 1080 gaattcaagg aggccttggt gcatcagaga cagctgctca ccatggtgag ccacggtcca 1140 gtggcgccga gaacgaagga acgcagcaca gtctccctcc ctgcccacag acacccagag 1200 cccccaaagt gcaaggactt tgtccctttt gggaagggca tccgggagga catcgcacgc 1260 aggttcccct tgtacccctt ggacttcact gatggcatta ttgggaaaaa caaggctgtg 1320 ggcaaataca tcaccaccac cctgttcctc tacttcgcct gcctcctgcc caccatcgct 1380 ttcgggtctc tcaatgacga gaacacagac ggggccatcg acgtgcagaa gaccatagcc 1440 gggcagagca tcgggggcct gctctacgcg ctcttctctg ggcagccatt ggtgattctg 1500 ctgaccaccg cgcccctggc gctctacatc caggtgattc gtgtcatctg tgatgactat 1560 gacctggact tcaactcctt ctacgcatgg acgggcctgt ggaatagttt cttccttgcg 1620 ctttatgcct ttttcaacct cagcctggtc atgagtctct tcaagaggtc gacggaggag 1680 atcatcgccc tcttcatttc catcacgttt gtgctggatg ccgtcaaggg cacggttaaa 1740 atcttctgga agtactacta tgggcattac ttggacgact atcacacaaa aaggacttca 1800 tcccttgtca gcctgtcagg cctcggcgcc agcctcaacg ccagcctcca cactgccctc 1860 aacgccagct tcctcgccag ccccacggag ctgccctcgg ccacacactc aggccaggcg 1920 accgccgtgc tcagcctcct catcatgctg ggcacgctct ggctgggcta caccctctac 1980 caattcaaga agagccccta cctgcacccc tgcgtgcgag agatcctgtc cgactgcgcc 2040 ctgcccatcg cggtgctcgc cttctccctc atcagctccc atggcttccg ggaaatcgag 2100 atgagcaagt tccgctacaa ccccagcgag agcccctttg cgatggcgca gatccagtcg 2160 ctgtccctga gggccgtcag cggtgccatg ggcctcggct tcctgctgtc catgctcttc 2220 ttcatcgagc agaacttggt ggccgccttg gtgaatgcac cggagaacag gctggtgaag 2280 ggcactgcct accactggga cctcctgctc ctcgccatca tcaacacagg gctgtctctg 2340 tttgggctgc cttggatcca tgccgcctac ccccactccc cgctgcacgt gcgagccctg 2400 gccttagtgg aggagcgtgt ggagaacgga cacatctatg acacgattgt gaacgtgaag 2460 gagacgcggc tgacctcgct gggcgccagc gtcctggtgg gcctgtccct gttgctgctg 2520 ccggtcccgc ttcagtggat ccccaagccc gtgctctatg gcctcttcct ctacatcgcg 2580 ctcacctccc tcgatggcaa ccagctcgtc cagcgcgtgg ccctgctgct caaggagcag 2640 actgcgtacc ccccgacaca ctacatccgg agggtgcccc agaggaagat ccactacttc 2700 acgggcctgc aggtgcttca gctgctgctg ctgtgtgcct tcggcatgag ctccctgccc 2760 tacatgaaga tgatctttcc cctcatcatg atcgccatga tccccatccg ctatatcctg 2820 ctgccccgaa tcattgaagc caagtacttg gatgtcatgg acgctgagca caggccttga 2880 ctggcagacc ctgcccacgc cccattcgcc agccctccac gtcctcccag gctggctctg 2940 gagctgtgag gggaggtgta ggtgtgtggg tgactgctct gtgctgcgcc ttctcatggc 3000 tgactcaggc ctggggcatc tgggcattgt aggggtgcag tggtatgtgc ccacccctct 3060 cccattatcc tttagcttta ggccaagagc gttgctcagg gcagcttctg cccagggtgg 3120 gtgggactga gcaggatgga ttttcttttg ataaaagagt cgatgcctga aagagaaacc 3180 atttccttga ttgtgtaagg aacttgctgg acgcacatta gagaataaag ctcctgtttc 3240 taggc 3245 <![CDATA[<210> 101]]> <![CDATA[<211> 2932]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 101]]> agaagcgccg gagcgccgcg tgaggagccc ggccgtgagt gcgcgagtgt gccatggccg 60 cggccaccag gcgcgtgttc catctgcagc cgtgcgaaaa ctctcccacc atgtcgcaga 120 atggatactt cgaggattca agctactaca agtgtgacac agatgacacc ttcgaagccc 180 gagaggagat cctgggggat gaggccttcg acactgccaa ctcctccatc gtgtctggcg 240 agagtatccg tttttttgtc aatgtcaacc ttgagatgca ggccaccaac actgagaatg 300 aagcgacttc cggtggctgt gtgctcctgc acacctcccg aaagtacctg aagttaaaga 360 acttcaagga agagatccgt gcgcaccgcg acctagatgg cttcctggcg caggccagca 420 tcgtcctgaa cgagacggcc acctccctgg ataacgtgct gcggaccatg cttcgccgct 480 tcgccaggga ccctgacaac aatgagccca actgcaacct ggacctgctc atggccatgc 540 tcttcaccga tgccggggca cccatgcggg gtaaagtcca cctgctgtca gataccatcc 600 aaggggtcac cgccacagtg acaggggtgc ggtaccagca gtcgtggctc tgcatcatct 660 gtaccatgaa ggccctacag aagcggcacg tgtgcatcag ccgcctggtt cgcccacaga 720 actgggggga gaattcctgt gaggttcggt tcgtcatcct ggtgctggcc ccacccaaga 780 tgaaaagcac taagactgcg atggaggtgg cgcgcacgtt tgccaccatg ttctcggata 840 tcgccttccg ccagaagctc ctggagaccc gcacagagga ggaattcaag gaggccttgg 900 tgcatcagag acagctgctc accatggtga gccacggtcc agtggcgccg agaacgaagg 960 aacgcagcac agtctccctc cctgcccaca gacacccaga gcccccaaag tgcaaggact 1020 ttgtcccttt tgggaagggc atccgggagg acatcgcacg caggttcccc ttgtacccct 1080 tggacttcac tgatggcatt attgggaaaa acaaggctgt gggcaaatac atcaccacca 1140 ccctgttcct ctacttcgcc tgcctcctgc ccaccatcgc tttcgggtct ctcaatgacg 1200 agaacacaga cggggccatc gtgattcgtg tcatctgtga tgactatgac ctggacttca 1260 actccttcta cgcatggacg ggcctgtgga atagtttctt ccttgcgctt tatgcctttt 1320 tcaacctcag cctggtcatg agtctcttca agaggtcgac ggaggagatc atcgccctct 1380 tcatttccat cacgtttgtg ctggatgccg tcaagggcac ggttaaaatc ttctggaagt 1440 actactatgg gcattacttg gacgactatc acacaaaaag gacttcatcc cttgtcagcc 1500 tgtcaggcct cggcgccagc ctcaacgcca gcctccacac tgccctcaac gccagcttcc 1560 tcgccagccc cacggagctg ccctcggcca cacactcagg ccaggcgacc gccgtgctca 1620 gcctcctcat catgctgggc acgctctggc tgggctacac cctctaccaa ttcaagaaga 1680 gcccctacct gcacccctgc gtgcgagaga tcctgtccga ctgcgccctg cccatcgcgg 1740 tgctcgcctt ctccctcatc agctcccatg gcttccggga aatcgagatg agcaagttcc 1800 gctacaaccc cagcgagagc ccctttgcga tggcgcagat ccagtcgctg tccctgaggg 1860 ccgtcagcgg tgccatgggc ctcggcttcc tgctgtccat gctcttcttc atcgagcaga 1920 acttggtggc cgccttggtg aatgcaccgg agaacaggct ggtgaagggc actgcctacc 1980 actgggacct cctgctcctc gccatcatca acacagggct gtctctgttt gggctgcctt 2040 ggatccatgc cgcctacccc cactccccgc tgcacgtgcg agccctggcc ttagtggagg 2100 agcgtgtgga gaacggacac atctatgaca cgattgtgaa cgtgaaggag acgcggctga 2160 cctcgctggg cgccagcgtc ctggtgggcc tgtccctgtt gctgctgccg gtcccgcttc 2220 agtggatccc caagcccgtg ctctatggcc tcttcctcta catcgcgctc acctccctcg 2280 atggcaacca gctcgtccag cgcgtggccc tgctgctcaa ggagcagact gcgtaccccc 2340 cgacacacta catccggagg gtgccccaga ggaagatcca ctacttcacg ggcctgcagg 2400 tgcttcagct gctgctgctg tgtgccttcg gcatgagctc cctgccctac atgaagatga 2460 tctttcccct catcatgatc gccatgatcc ccatccgcta tatcctgctg ccccgaatca 2520 ttgaagccaa gtacttggat gtcatggacg ctgagcacag gccttgactg gcagaccctg 2580 cccacgcccc attcgccagc cctccacgtc ctcccaggct ggctctggag ctgtgagggg 2640 aggtgtaggt gtgtgggtga ctgctctgtg ctgcgccttc tcatggctga ctcaggcctg 2700 gggcatctgg gcattgtagg ggtgcagtgg tatgtgccca cccctctccc attatccttt 2760 agctttaggc caagagcgtt gctcagggca gcttctgccc agggtgggtg ggactgagca 2820 ggatggattt tcttttgata aaagagtcga tgcctgaaag agaaaccatt tccttgattg 2880 tgtaaggaac ttgctggacg cacattagag aataaagctc ctgtttctag gc 2932 <![CDATA[<210> 102]]> <![CDATA[<211> 5577]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 102]]> ggatcacagc ccttccccga tcctctccgt gggagccagc gagcctctct ccctgatctt 60 acgtgctcaa gggagctcac acgttcacca actcaccctt gaagtcatct caagaacaaa 120 agacaactga aagaagctgt tgtgaaggca gagcagcatc tgctgaagag acagaaacca 180 gccccagagg tgtcacagga aggcaccagc aaggacattg gtctttgatt tgattcagca 240 gtcctgtcaa gtataaatgt gatggctgtg ctgcctggcc ctctgcagct gctgggagtg 300 ctgcttacca tttccctgag ttccatcagg ctcattcagg ctggtgccta ctatgggatc 360 aagccgctgc cacctcaaat tcctcctcag atgccaccac aaattccaca ataccagccc 420 ctgggtcagc aagtacctca catgcctttg gccaaagatg gccttgccat gggcaaggag 480 atgccccact tgcagtatgg caaagagtat ccacacctac cccaatatat gaaggaaatt 540 caaccggcgc caagaatggg caaggaagcc gtacccaaga aaggcaaaga aataccatta 600 gccagtttac gaggggaaca aggtccccgt ggagagcctg gcccaagagg accacctggg 660 ccccctggtt tgccaggtca tgggatacct ggaattaaag gaaaaccagg gccacaggga 720 tatccaggag ttggaaagcc aggtatgcct ggaatgccag ggaagccagg agccatgggc 780 atgcctgggg caaaaggaga aattggacag aaaggggaaa ttgggcctat ggggatccca 840 ggaccacaag gacctccagg gcctcatgga cttcctggca ttgggaagcc aggtgggcca 900 gggttaccag ggcaaccagg accaaagggt gatcgaggac ccaaaggact accaggacct 960 caaggccttc ggggtcctaa aggagacaag ggcttcggga tgccaggtgc gccaggtgta 1020 aaggggcctc cagggatgca cggccctccc ggccctgttg gactgccagg agtgggcaaa 1080 ccaggagtga caggcttccc tgggccccag ggccccctgg gaaagccagg ggctccagga 1140 gaacctgggc cacaaggccc tattggggta ccgggggttc aaggacctcc tgggataccc 1200 ggaattggaa agccaggcca ggatgggatc ccaggccagc caggatttcc aggtggcaaa 1260 ggggagcaag gactgccagg gctaccagga cccccaggcc ttccagggat tgggaaacca 1320 ggcttcccag gacccaaagg tgaccggggc atgggaggtg ttcctggggc tcttggacca 1380 agaggggaga aaggaccaat aggtgcccca ggaatagggg gtcctccagg agagccaggc 1440 ctgcctggaa tcccaggtcc tatgggccct ccaggtgcta ttggttttcc tggacccaaa 1500 ggagaaggtg ggattgtagg gccacagggg ccaccaggtc ccaagggtga gccagggctt 1560 caaggcttcc caggaaagcc aggtttcctt ggtgaagtag ggcctcctgg catgaggggt 1620 ttgccaggtc ccatagggcc caagggggaa gctgggcaaa aaggtgtacc aggactccct 1680 ggtgttccag ggcttctcgg acctaaggga gagccaggaa tcccagggga tcagggttta 1740 cagggccccc caggtatccc agggattggg ggccctagtg gccccattgg accacctggg 1800 attccaggcc ccaaagggga gccgggcctc ccagggcccc ctgggttccc tggtataggg 1860 aaacccggag tggcaggact tcatggcccc ccagggaagc ctggtgccct tggtcctcaa 1920 ggccagcctg gccttccagg acccccaggc cctccaggac ctccaggacc cccagctgtg 1980 atgcccccta caccaccacc ccagggagag tatctgccag atatggggct gggaattgat 2040 ggcgtgaaac ccccccatgc ctacggggct aagaaaggca agaatggagg gccagcctat 2100 gagatgcctg catttaccgc cgagctaacc gcacctttcc caccggtggg ggccccagtg 2160 aagtttaaca aactgctgta taacggcaga cagaactaca acccgcagac aggcatcttc 2220 acctgtgagg tccctggtgt ctactacttt gcataccacg ttcactgcaa ggggggcaac 2280 gtgtgggttg ctctattcaa gaacaacgag cccgtgatgt acacgtacga cgagtacaaa 2340 aagggcttcc tggaccaggc atctgggagt gcagtgctgc tgctcaggcc cggagaccgg 2400 gtgttcctcc agatgccctc agaacaggct gcaggactgt atgccgggca gtatgtccac 2460 tcctcctttt caggatattt attgtatccc atgtaaaaac aaaaaaacaa aaaacaaaga 2520 aaagaaagag attttataga agaaaatgac acaccaaaaa atccaaatga aaaacataat 2580 tgcttcaaaa cacttacaca gttggaaagt tatatgtaag tgaaaatttg gaccattgtg 2640 tacaaataaa aactaagatg catgtttaat actccacaca gcagcctgta attgcgaatg 2700 atgggataga gttatgtatc aagtactgac acttggttgt acccactgga atcatattag 2760 ctgttttatg ttatatgctt ccacagtaac ctgcttattc agatcagtca aaatatatca 2820 gtatgaaaga tcatagctaa tgaaaggcac tcactcatat tgtttacttt aaaatattta 2880 taaatatgcc ttaaagaaat acaaatgata acaattacat accgtattta cttgcttaat 2940 ttcctctgta tttgtgtaga tactttgaca tggaatatat ggtggggaga cccgtagtgt 3000 taccgcccca gtgggagggg gccctgggga ccctggtaat gctttagtca aagggatatc 3060 tctcttgtat cagaggctgt gtcttttagt aacaggagtc ctcgtcagaa ttgcgtgtct 3120 gttgtctcta aaagaatggg tgaaccaatc ggcctttgtg aatttattca gtgccttctc 3180 tgtaccaagc actgggtaag gcacttttgt ggagcattag acagtaaccc tcaaggagct 3240 agagaaccgg atgggagaca tgagcagtaa ttaactcact tgttccccag agtttctatt 3300 tgttttgatt ttctttttct gtgacttatt ttcctatttt ctttcctcca tgtaattttc 3360 actatggccc aactaatata aacacctgga aattacaagg aaaaaaaatt cttcctctaa 3420 taactttcca aatttgtgga atatttattt gtaatagcag ttatcagtta tgcttatata 3480 gcattaaaaa ttctcctcct ttgactacac acacaaccac agtgtggttc taatcatgga 3540 gatatcagta atttttagta actgaatttt gaggacattt ctctgtttag catgtatgca 3600 aactgatatg taatctgagg ttccaaagtc aatttttttc tttttttttt gagatggagt 3660 cttactctgt cacccaggct ggagtgcagt agcacgatct tggcttactg caacctctac 3720 ctcctaggtt caagcaattg tcctgtctca gcctcccgag tactgggact actgtcttgc 3780 gccaccatgc ctggctaatt tttgtatatt tagtaaagat gggttttcgc catgttggcc 3840 aggctggtct caaactcctg gcctcaagtg atgcacctgc ctcagccttc caaagtgctg 3900 ggattacagg catgagccac cgtgcccggc caaagtcagc tttcaaaatc caagccataa 3960 ttggtgaggg gggagtttca gaattacata gaaaaattaa tatttgaaaa aataattctg 4020 aaatttcgaa tttaaaaaca gatgtgctgc ttctgggtgt aggtagtaaa agtataggaa 4080 aagaactgtt tccttagaag cggactgtgg aagggctatg tagaatgtca aagggcaaca 4140 agagcctgtg tttttaatgt catcctgtac tcggcacaaa tcaaaggcca atacaagtct 4200 gaaaagcaga aataaatatt tttccaggtt tttgcttggg cacatactaa ctgctttggg 4260 cattctaatc tggtctccaa acaccaaaga cccatttcga gcctgctatt agcctgctgc 4320 tgactctatc acttggagca ataatgtggg gttatggtgg tggaatcttg tatatttttg 4380 tcaaaaataa aaccatgagt taaggggata gatatagatg gaaaaataca caaataaata 4440 cggtatgaaa acacatggaa atgtgtcttt gtcaaatctg aatcattatt accatcacaa 4500 aaattcttct cttggccaat atctcatttc cctatatagt atacaagcac catttcttct 4560 caatttttaa gaagagaaat tagtccatta ccacaggggt tcttgtcact actaattata 4620 caacaatctt ttcccaacaa aaagatgtcc tccacaacct ttgttttcaa agcagacagc 4680 atctatgtgg ccaaatatac tttgggttgt tcttgaggat actggttttg ggctgatgac 4740 tatggtgggc agcatggatc cattgggctc cttctgctaa acagccacat tgaaatggtt 4800 taaaagcaag tcagatcagg tgatttgtaa aattgtattt atctgtacat gtatgggctt 4860 ttaattccca ccaagaaaga gagaaattat ctttttagtt aaaaccaaat ttcacttttc 4920 aaaatatctt ccaacttatt tattggttgt cactcaattg cctatatata tatatatatg 4980 tgtgtgtgtg tgtgtgtgcg cgtgagcgca cgtgtgtgta tgcgtgcgca tgtgtgtgta 5040 tgtgtattat cagacatagg tttctaactt ttagatagaa gaggagcaac atctatgcca 5100 aatactgtgc attctacaat ggtgctaatc tcagacctaa atgatactcc atttaattta 5160 aaaaagagtt ttaaataatt atctatgtgc ctgtatttcc cttttgagtg ctgcacaaca 5220 tgttaacata ttagtgtaaa agcagatgaa acaaccacgt gttctaaagt ctagggattg 5280 tgctataatc cctatttagt tcaaaattaa ccagaattct tccatgtgaa atggaccaaa 5340 ctcatattat tgttatgtaa atacagagtt ttaatgcagt atgacatccc acaggggaaa 5400 agaatgtctg tagtgggtga ctgttatcaa atattttata gaatacaatg aacggtgaac 5460 agactggtaa cttgtttgag ttcccatgac agatttgaga cttgtcaata gcaaatcatt 5520 tttgtattta aatttttgta ctgatttgaa aaacatcatt aaatatcttt aaaagta 5577 <![CDATA[<210> 103]]> <![CDATA[<211> 5515]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 103]]> ggatcacagc ccttccccga tcctctccgt gggagccagc gagcctctct ccctgatctt 60 acgtgctcaa gaagctgttg tgaaggcaga gcagcatctg ctgaagagac agaaaccagc 120 cccagaggtg tcacaggaag gcaccagcaa ggacattggt ctttgatttg attcagcagt 180 cctgtcaagt ataaatgtga tggctgtgct gcctggccct ctgcagctgc tgggagtgct 240 gcttaccatt tccctgagtt ccatcaggct cattcaggct ggtgcctact atgggatcaa 300 gccgctgcca cctcaaattc ctcctcagat gccaccacaa attccacaat accagcccct 360 gggtcagcaa gtacctcaca tgcctttggc caaagatggc cttgccatgg gcaaggagat 420 gccccacttg cagtatggca aagagtatcc acacctaccc caatatatga aggaaattca 480 accggcgcca agaatgggca aggaagccgt acccaagaaa ggcaaagaaa taccattagc 540 cagtttacga ggggaacaag gtccccgtgg agagcctggc ccaagaggac cacctgggcc 600 ccctggtttg ccaggtcatg ggatacctgg aattaaagga aaaccagggc cacagggata 660 tccaggagtt ggaaagccag gtatgcctgg aatgccaggg aagccaggag ccatgggcat 720 gcctggggca aaaggagaaa ttggacagaa aggggaaatt gggcctatgg ggatcccagg 780 accacaagga cctccagggc ctcatggact tcctggcatt gggaagccag gtgggccagg 840 gttaccaggg caaccaggac caaagggtga tcgaggaccc aaaggactac caggacctca 900 aggccttcgg ggtcctaaag gagacaaggg cttcgggatg ccaggtgcgc caggtgtaaa 960 ggggcctcca gggatgcacg gccctcccgg ccctgttgga ctgccaggag tgggcaaacc 1020 aggagtgaca ggcttccctg ggccccaggg ccccctggga aagccagggg ctccaggaga 1080 acctgggcca caaggcccta ttggggtacc gggggttcaa ggacctcctg ggatacccgg 1140 aattggaaag ccaggccagg atgggatccc aggccagcca ggatttccag gtggcaaagg 1200 ggagcaagga ctgccagggc taccaggacc cccaggcctt ccagggattg ggaaaccagg 1260 cttcccagga cccaaaggtg accggggcat gggaggtgtt cctggggctc ttggaccaag 1320 aggggagaaa ggaccaatag gtgccccagg aatagggggt cctccaggag agccaggcct 1380 gcctggaatc ccaggtccta tgggccctcc aggtgctatt ggttttcctg gacccaaagg 1440 agaaggtggg attgtagggc cacaggggcc accaggtccc aagggtgagc cagggcttca 1500 aggcttccca ggaaagccag gtttccttgg tgaagtaggg cctcctggca tgaggggttt 1560 gccaggtccc atagggccca agggggaagc tgggcaaaaa ggtgtaccag gactccctgg 1620 tgttccaggg cttctcggac ctaagggaga gccaggaatc ccaggggatc agggtttaca 1680 gggcccccca ggtatcccag ggattggggg ccctagtggc cccattggac cacctgggat 1740 tccaggcccc aaaggggagc cgggcctccc agggccccct gggttccctg gtatagggaa 1800 acccggagtg gcaggacttc atggcccccc agggaagcct ggtgcccttg gtcctcaagg 1860 ccagcctggc cttccaggac ccccaggccc tccaggacct ccaggacccc cagctgtgat 1920 gccccctaca ccaccacccc agggagagta tctgccagat atggggctgg gaattgatgg 1980 cgtgaaaccc ccccatgcct acggggctaa gaaaggcaag aatggagggc cagcctatga 2040 gatgcctgca tttaccgccg agctaaccgc acctttccca ccggtggggg ccccagtgaa 2100 gtttaacaaa ctgctgtata acggcagaca gaactacaac ccgcagacag gcatcttcac 2160 ctgtgaggtc cctggtgtct actactttgc ataccacgtt cactgcaagg ggggcaacgt 2220 gtgggttgct ctattcaaga acaacgagcc cgtgatgtac acgtacgacg agtacaaaaa 2280 gggcttcctg gaccaggcat ctgggagtgc agtgctgctg ctcaggcccg gagaccgggt 2340 gttcctccag atgccctcag aacaggctgc aggactgtat gccgggcagt atgtccactc 2400 ctccttttca ggatatttat tgtatcccat gtaaaaacaa aaaaacaaaa aacaaagaaa 2460 agaaagagat tttatagaag aaaatgacac accaaaaaat ccaaatgaaa aacataattg 2520 cttcaaaaca cttacacagt tggaaagtta tatgtaagtg aaaatttgga ccattgtgta 2580 caaataaaaa ctaagatgca tgtttaatac tccacacagc agcctgtaat tgcgaatgat 2640 gggatagagt tatgtatcaa gtactgacac ttggttgtac ccactggaat catattagct 2700 gttttatgtt atatgcttcc acagtaacct gcttattcag atcagtcaaa atatatcagt 2760 atgaaagatc atagctaatg aaaggcactc actcatattg tttactttaa aatatttata 2820 aatatgcctt aaagaaatac aaatgataac aattacatac cgtatttact tgcttaattt 2880 cctctgtatt tgtgtagata ctttgacatg gaatatatgg tggggagacc cgtagtgtta 2940 ccgccccagt gggagggggc cctggggacc ctggtaatgc tttagtcaaa gggatatctc 3000 tcttgtatca gaggctgtgt cttttagtaa caggagtcct cgtcagaatt gcgtgtctgt 3060 tgtctctaaa agaatgggtg aaccaatcgg cctttgtgaa tttattcagt gccttctctg 3120 taccaagcac tgggtaaggc acttttgtgg agcattagac agtaaccctc aaggagctag 3180 agaaccggat gggagacatg agcagtaatt aactcacttg ttccccagag tttctatttg 3240 ttttgatttt ctttttctgt gacttatttt cctattttct ttcctccatg taattttcac 3300 tatggcccaa ctaatataaa cacctggaaa ttacaaggaa aaaaaattct tcctctaata 3360 actttccaaa tttgtggaat atttatttgt aatagcagtt atcagttatg cttatatagc 3420 attaaaaatt ctcctccttt gactacacac acaaccacag tgtggttcta atcatggaga 3480 tatcagtaat ttttagtaac tgaattttga ggacatttct ctgtttagca tgtatgcaaa 3540 ctgatatgta atctgaggtt ccaaagtcaa tttttttctt ttttttttga gatggagtct 3600 tactctgtca cccaggctgg agtgcagtag cacgatcttg gcttactgca acctctacct 3660 cctaggttca agcaattgtc ctgtctcagc ctcccgagta ctgggactac tgtcttgcgc 3720 caccatgcct ggctaatttt tgtatattta gtaaagatgg gttttcgcca tgttggccag 3780 gctggtctca aactcctggc ctcaagtgat gcacctgcct cagccttcca aagtgctggg 3840 attacaggca tgagccaccg tgcccggcca aagtcagctt tcaaaatcca agccataatt 3900 ggtgaggggg gagtttcaga attacataga aaaattaata tttgaaaaaa taattctgaa 3960 atttcgaatt taaaaacaga tgtgctgctt ctgggtgtag gtagtaaaag tataggaaaa 4020 gaactgtttc cttagaagcg gactgtggaa gggctatgta gaatgtcaaa gggcaacaag 4080 agcctgtgtt tttaatgtca tcctgtactc ggcacaaatc aaaggccaat acaagtctga 4140 aaagcagaaa taaatatttt tccaggtttt tgcttgggca catactaact gctttgggca 4200 ttctaatctg gtctccaaac accaaagacc catttcgagc ctgctattag cctgctgctg 4260 actctatcac ttggagcaat aatgtggggt tatggtggtg gaatcttgta tatttttgtc 4320 aaaaataaaa ccatgagtta aggggataga tatagatgga aaaatacaca aataaatacg 4380 gtatgaaaac acatggaaat gtgtctttgt caaatctgaa tcattattac catcacaaaa 4440 attcttctct tggccaatat ctcatttccc tatatagtat acaagcacca tttcttctca 4500 atttttaaga agagaaatta gtccattacc acaggggttc ttgtcactac taattataca 4560 acaatctttt cccaacaaaa agatgtcctc cacaaccttt gttttcaaag cagacagcat 4620 ctatgtggcc aaatatactt tgggttgttc ttgaggatac tggttttggg ctgatgacta 4680 tggtgggcag catggatcca ttgggctcct tctgctaaac agccacattg aaatggttta 4740 aaagcaagtc agatcaggtg atttgtaaaa ttgtatttat ctgtacatgt atgggctttt 4800 aattcccacc aagaaagaga gaaattatct ttttagttaa aaccaaattt cacttttcaa 4860 aatatcttcc aacttattta ttggttgtca ctcaattgcc tatatatata tatatatgtg 4920 tgtgtgtgtg tgtgtgcgcg tgagcgcacg tgtgtgtatg cgtgcgcatg tgtgtgtatg 4980 tgtattatca gacataggtt tctaactttt agatagaaga ggagcaacat ctatgccaaa 5040 tactgtgcat tctacaatgg tgctaatctc agacctaaat gatactccat ttaatttaaa 5100 aaagagtttt aaataattat ctatgtgcct gtatttccct tttgagtgct gcacaacatg 5160 ttaacatatt agtgtaaaag cagatgaaac aaccacgtgt tctaaagtct agggattgtg 5220 ctataatccc tatttagttc aaaattaacc agaattcttc catgtgaaat ggaccaaact 5280 catattattg ttatgtaaat acagagtttt aatgcagtat gacatcccac aggggaaaag 5340 aatgtctgta gtgggtgact gttatcaaat attttataga atacaatgaa cggtgaacag 5400 actggtaact tgtttgagtt cccatgacag atttgagact tgtcaatagc aaatcatttt 5460 tgtatttaaa tttttgtact gatttgaaaa acatcattaa atatctttaa aagta 5515 <![CDATA[<210> 104]]> <![CDATA[<211> 4524]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<40]]>0> 104]]> <br/><![CDATA[actccggcag ccgcgagggg cggccggcag agcgacgcgg aaccccgccg gcgcggaccc 60 cggaccccaa cgccgcccgc ccagccgcgg acgcccctgc ccggagccct cgccgcccgg 120 gccgccctcg agggccggga gcggcgcccg gcggccgcgc ccgcaggccc tgcctctgct 180 ggaaccttcc caggcccctc cgacctgaaa gcacgtccac ggacgccatg ctggggactc 240 tgacacccct gtcttcgctg ctgctgctgc tactgaaatg cctctaccgc tgctgccgat 300 ggacctgaag ggagagcccg gcccccctgg gaagcccggg cctcggggtc cccctggccc 360 ccctggcttc ccaggaaaac caggcatggg aaagccagga ctccatgggc agcctggccc 420 tgctgggccc cctggcttct cccggatggg caaggctggt cccccagggc tccctggcaa 480 ggtcgggcca ccagggcagc cggggcttcg gggggagcca ggaatacgag gggaccaggg 540 cctccgggga cccccaggac cccctggcct cccgggcccc tcaggcatta ctatccctgg 600 aaaaccaggt gcccaagggg tgccagggcc cccaggattc cagggggaac cagggcccca 660 gggggagcct gggcccccag gtgatcgagg cctcaagggg gataatggag tgggccagcc 720 cgggctgcct ggggccccag ggcagggggg tgcccccggc ccccccggcc tccctggtcc 780 agctggctta ggcaaacctg gtttggatgg gcttcctggg gccccaggag acaagggtga 840 gtctgggcct cctggagttc caggccccag gggggagcca ggagctgtgg gcccaaaagg 900 acctcctgga gtagacggtg tgggagtccc aggggcagca gggttgccag gaccacaggg 960 cccatcaggg gccaaagggg agccagggac ccggggcccc cctgggctga taggccccac 1020 tggctatggg atgccaggac tgccaggccc caagggggac aggggcccag ctggggtccc 1080 aggactcttg ggggacaggg gtgagccagg ggaggatggg gagccagggg agcagggccc 1140 acagggtctt gggggtcccc ctggacttcc tgggtctgca gggcttcctg gcagacgtgg 1200 gccccctggg cctaagggtg aggcagggcc tggaggaccc ccaggagtgc ctggcattcg 1260 aggtgaccag gggcctagtg gcctggctgg gaaaccaggg gtcccaggtg agaggggact 1320 tcctggggcc catggacccc ctggaccaac tgggcccaag ggtgagccgg gtttcacggg 1380 tcgccctgga ggaccagggg tggcaggagc cctggggcag aaaggtgact tggggctccc 1440 tgggcagcct ggcctgaggg gtccctcagg aatcccagga ctccagggtc cagctggccc 1500 tattgggccc caaggcctgc cgggcctgaa gggggaacca ggcctgccag ggccccctgg 1560 agaggggaga gcaggggaac ctggcacggc tgggcccacg gggcccccag gggtccctgg 1620 ctcccctgga atcacgggcc ctccggggcc tcccgggccc ccgggacccc ctggtgcccc 1680 tggggccttc gatgagactg gcatcgcagg cttgcacctg cccaacggcg gtgtggaggg 1740 tgccgtgctg ggcaaggggg gcaagccaca gtttgggctg ggcgagctgt ctgcccatgc 1800 cacaccggcc ttcactgcgg tgctcacctc gcccttcccc gcctcgggca tgcccgtgaa 1860 atttgaccgg actctctaca atggccacag cggctacaac ccagccactg gcatcttcac 1920 ctgccctgtg ggcggcgtct actactttgc ttaccatgtg cacgtcaagg gcaccaacgt 1980 gtgggtggcc ctgtacaaga acaacgtgcc ggccacctat acctacgatg agtacaagaa 2040 gggctacctg gaccaggcat ctggtggggc cgtgctccag ctgcggccca acgaccaggt 2100 ctgggtgcag atgccgtcgg accaggccaa cggcctctac tccacggagt acatccactc 2160 ctccttttca ggattcttgc tctgccccac ataacccgcg gggggggtcc tgctgccctg 2220 gcctcctccc ctttagtggt agagcgacct tttcaattac aaagaacctc ctggaaaaaa 2280 aaacaaaagc tgaacagagg cggccgtggc cttggcccga ggagactaac ttgctttctc 2340 cctgcatgca ggctgagatt gtttctggaa ggggctggcc tgagtttctt tcccccaaat 2400 gtctgtgcag tgtcagggct gcaccccata ggccctgagg cacacagccc agccccttgt 2460 gagtcctggc ctctgctggg ccctgaagga gctgagaggg agctcaactc cccaccccgc 2520 cacgtgggga gacagccctt cccactggct ccctgatggc acctgctgga ggaaaggggc 2580 acggcctccc tcacagccct tggctggggc tcctccagct ccccctggga cctccagcat 2640 atgacagtgg actaaggact gtggggtttt cctccaaggg gaagggagaa gaggggacca 2700 tcgaggtggc gagtgtggac accctgccag gactgcagcc cccatggtga tgctgtggca 2760 tcagacatgt ccgtggtggg cacagtgcct gttgccctgg gaaagggcaa cctccctttc 2820 actgctccag tggcagccat ggggaaggca gtttgtgagg gcttggggca cagacctggg 2880 gcaggaggca gctcttcacg ttcatccctg tctctcccgg gctgcccccg ccagctctgg 2940 ctgtttagct tgagggcagc acagaggccc ctgggacacc tacaggccag aaagatcaac 3000 ctctgtgaag tgtctagaag tatctagtgc agatggtggc ggaggcagaa tcgaccatca 3060 gcaaacatga gcactcttcc ctttctcccc ttccacctgc tgcgggctgg gctggttttc 3120 tcaatacaaa attgtaagag gatccttgtc accccagcca ggtatcccca aggcagagca 3180 cctctcgttt ggccctctga acaaggtgca cgcgagctgg gggatgaaga cggctcccac 3240 ttccttttcc ttaataagaa ccatatggtg ggtgtatgtg tgtacaagag gggttcatct 3300 gtgggggctt cctctccttc caccctctgg ttccaatttc ctgttctaag caggactagg 3360 gcccaggagg ctaaggctgg gagagaaagg gtgccaacag gtcccttggg aatgagttgg 3420 ctctggacgt ttctgccctg ttccccgatc agagctcctc tgcaggaaac aggcaggatg 3480 cccctcccaa cccctcagtc cctacgtcaa gcggagtgga taaggctgag atgagtgctg 3540 ggagtggtgg acattcctgc tcgtgcaaag atggccactt tccccgcagc tgcagggcct 3600 cgcgctcggc cctcgccagg ccagccccac tccttgtacc aagtgtgaac tggggtcatt 3660 cggtctgtga tctcgttgca ctgctccaag tctggctgtg tccaggcggt ccatgttgaa 3720 aatggaggat ggctgctgac ttctgactgg ctgagcagtg ggttccttca ggttccttgc 3780 caaccctcct cccctgccca caacttctcc aaacaaagca ggctgtttgc tcacttcttc 3840 aaaaggagga atgataaccc aaatctgccc aagtgacact tgagaaggtt ttggctgggg 3900 ttcctggtgg atttcttact acctaacgcc caagaaaacc aactaaggac tctcaaacca 3960 tacctggtgg gggttcttcg ctcaacctct tcttccctag gtcaaagcca ctatcatctg 4020 atgtgttagg gatgggttct gattggcaga aattaatcag ctcccaatgg gagcccacgg 4080 aactaagtag ggtcccaaga aaaaaaacgg gagctatttc acagagctga gcttctgcca 4140 aatttcattc ctcaaacctt tcaggagggg tggttggcgt ttctaaaatg tttatgggat 4200 ttgagttgca ggtgtccact taactgacta gctttgataa acaatgtcag attttaacta 4260 tgaaaacgac attaccttgt gcatttttat attgattcct attttttttt taagattaaa 4320 gtttaaatgt tttccactag tcatttcact tctaacttgg tataggaagc ttagctctct 4380 acatacctat catgtgccct gtatcacaga agattcagga aaaatgcact tgggaatcaa 4440 agaaaatgga acttcttttt gaaaagacaa gcaaccatgt taactgtatt gacacatcct 4500 caataaaacc tgttgtataa aaca 4524 <![CDATA[<210> 105]]> <![CDATA[<211> 4669]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 105]]> actccggcag ccgcgagggg cggccggcag agcgacgcgg aaccccgccg gcgcggaccc 60 cggaccccaa cgccgcccgc ccagccgcgg acgcccctgc ccggagccct cgccgcccgg 120 gccgccctcg agggccggga gcggcgcccg gcggccgcgc ccgcaggccc tgcctctgct 180 ggaaccttcc caggcccctc cgacctgaaa gcacgtccac ggacgccatg ctggggactc 240 tgacacccct gtcttcgctg ctgctgctgc tactggtgct ggtgctgggg tgtgggccgc 300 gggcgtcctc tggtggcggg gccggtgggg cggcgggcta tgccccagtg aagtacatcc 360 agcccatgca gaaaggacct gtgggaccgc ccttccgtga gggcaaaggc cagtacctgg 420 aaatgcctct accgctgctg ccgatggacc tgaagggaga gcccggcccc cctgggaagc 480 ccgggcctcg gggtccccct ggcccccctg gcttcccagg aaaaccaggc atgggaaagc 540 caggactcca tgggcagcct ggccctgctg ggccccctgg cttctcccgg atgggcaagg 600 ctggtccccc agggctccct ggcaaggtcg ggccaccagg gcagccgggg cttcgggggg 660 agccaggaat acgaggggac cagggcctcc ggggaccccc aggaccccct ggcctcccgg 720 gcccctcagg cattactatc cctggaaaac caggtgccca aggggtgcca gggcccccag 780 gattccaggg ggaaccaggg ccccaggggg agcctgggcc cccaggtgat cgaggcctca 840 agggggataa tggagtgggc cagcccgggc tgcctggggc cccagggcag gggggtgccc 900 ccggcccccc cggcctccct ggtccagctg gcttaggcaa acctggtttg gatgggcttc 960 ctggggcccc aggagacaag ggtgagtctg ggcctcctgg agttccaggc cccagggggg 1020 agccaggagc tgtgggccca aaaggacctc ctggagtaga cggtgtggga gtcccagggg 1080 cagcagggtt gccaggacca cagggcccat caggggccaa aggggagcca gggacccggg 1140 gcccccctgg gctgataggc cccactggct atgggatgcc aggactgcca ggccccaagg 1200 gggacagggg cccagctggg gtcccaggac tcttggggga caggggtgag ccaggggagg 1260 atggggagcc aggggagcag ggcccacagg gtcttggggg tccccctgga cttcctgggt 1320 ctgcagggct tcctggcaga cgtgggcccc ctgggcctaa gggtgaggca gggcctggag 1380 gacccccagg agtgcctggc attcgaggtg accaggggcc tagtggcctg gctgggaaac 1440 caggggtccc aggtgagagg ggacttcctg gggcccatgg accccctgga ccaactgggc 1500 ccaagggtga gccgggtttc acgggtcgcc ctggaggacc aggggtggca ggagccctgg 1560 ggcagaaagg tgacttgggg ctccctgggc agcctggcct gaggggtccc tcaggaatcc 1620 caggactcca gggtccagct ggccctattg ggccccaagg cctgccgggc ctgaaggggg 1680 aaccaggcct gccagggccc cctggagagg ggagagcagg ggaacctggc acggctgggc 1740 ccacggggcc cccaggggtc cctggctccc ctggaatcac gggccctccg gggcctcccg 1800 ggcccccggg accccctggt gcccctgggg ccttcgatga gactggcatc gcaggcttgc 1860 acctgcccaa cggcggtgtg gagggtgccg tgctgggcaa ggggggcaag ccacagtttg 1920 ggctgggcga gctgtctgcc catgccacac cggccttcac tgcggtgctc acctcgccct 1980 tccccgcctc gggcatgccc gtgaaatttg accggactct ctacaatggc cacagcggct 2040 acaacccagc cactggcatc ttcacctgcc ctgtgggcgg cgtctactac tttgcttacc 2100 atgtgcacgt caagggcacc aacgtgtggg tggccctgta caagaacaac gtgccggcca 2160 cctataccta cgatgagtac aagaagggct acctggacca ggcatctggt ggggccgtgc 2220 tccagctgcg gcccaacgac caggtctggg tgcagatgcc gtcggaccag gccaacggcc 2280 tctactccac ggagtacatc cactcctcct tttcaggatt cttgctctgc cccacataac 2340 ccgcgggggg ggtcctgctg ccctggcctc ctccccttta gtggtagagc gaccttttca 2400 attacaaaga acctcctgga aaaaaaaaca aaagctgaac agaggcggcc gtggccttgg 2460 cccgaggaga ctaacttgct ttctccctgc atgcaggctg agattgtttc tggaaggggc 2520 tggcctgagt ttctttcccc caaatgtctg tgcagtgtca gggctgcacc ccataggccc 2580 tgaggcacac agcccagccc cttgtgagtc ctggcctctg ctgggccctg aaggagctga 2640 gagggagctc aactccccac cccgccacgt ggggagacag cccttcccac tggctccctg 2700 atggcacctg ctggaggaaa ggggcacggc ctccctcaca gcccttggct ggggctcctc 2760 cagctccccc tgggacctcc agcatatgac agtggactaa ggactgtggg gttttcctcc 2820 aaggggaagg gagaagaggg gaccatcgag gtggcgagtg tggacaccct gccaggactg 2880 cagcccccat ggtgatgctg tggcatcaga catgtccgtg gtgggcacag tgcctgttgc 2940 cctgggaaag ggcaacctcc ctttcactgc tccagtggca gccatgggga aggcagtttg 3000 tgagggcttg gggcacagac ctggggcagg aggcagctct tcacgttcat ccctgtctct 3060 cccgggctgc ccccgccagc tctggctgtt tagcttgagg gcagcacaga ggcccctggg 3120 acacctacag gccagaaaga tcaacctctg tgaagtgtct agaagtatct agtgcagatg 3180 gtggcggagg cagaatcgac catcagcaaa catgagcact cttccctttc tccccttcca 3240 cctgctgcgg gctgggctgg ttttctcaat acaaaattgt aagaggatcc ttgtcacccc 3300 agccaggtat ccccaaggca gagcacctct cgtttggccc tctgaacaag gtgcacgcga 3360 gctgggggat gaagacggct cccacttcct tttccttaat aagaaccata tggtgggtgt 3420 atgtgtgtac aagaggggtt catctgtggg ggcttcctct ccttccaccc tctggttcca 3480 atttcctgtt ctaagcagga ctagggccca ggaggctaag gctgggagag aaagggtgcc 3540 aacaggtccc ttgggaatga gttggctctg gacgtttctg ccctgttccc cgatcagagc 3600 tcctctgcag gaaacaggca ggatgcccct cccaacccct cagtccctac gtcaagcgga 3660 gtggataagg ctgagatgag tgctgggagt ggtggacatt cctgctcgtg caaagatggc 3720 cactttcccc gcagctgcag ggcctcgcgc tcggccctcg ccaggccagc cccactcctt 3780 gtaccaagtg tgaactgggg tcattcggtc tgtgatctcg ttgcactgct ccaagtctgg 3840 ctgtgtccag gcggtccatg ttgaaaatgg aggatggctg ctgacttctg actggctgag 3900 cagtgggttc cttcaggttc cttgccaacc ctcctcccct gcccacaact tctccaaaca 3960 aagcaggctg tttgctcact tcttcaaaag gaggaatgat aacccaaatc tgcccaagtg 4020 acacttgaga aggttttggc tggggttcct ggtggatttc ttactaccta acgcccaaga 4080 aaaccaacta aggactctca aaccatacct ggtgggggtt cttcgctcaa cctcttcttc 4140 cctaggtcaa agccactatc atctgatgtg ttagggatgg gttctgattg gcagaaatta 4200 atcagctccc aatgggagcc cacggaacta agtagggtcc caagaaaaaa aacgggagct 4260 atttcacaga gctgagcttc tgccaaattt cattcctcaa acctttcagg aggggtggtt 4320 ggcgtttcta aaatgtttat gggatttgag ttgcaggtgt ccacttaact gactagcttt 4380 gataaacaat gtcagatttt aactatgaaa acgacattac cttgtgcatt tttatattga 4440 ttcctatttt ttttttaaga ttaaagttta aatgttttcc actagtcatt tcacttctaa 4500 cttggtatag gaagcttagc tctctacata cctatcatgt gccctgtatc acagaagatt 4560 caggaaaaat gcacttggga atcaaagaaa atggaacttc tttttgaaaa gacaagcaac 4620 catgttaact gtattgacac atcctcaata aaacctgttg tataaaaca 4669 <![CDATA[<210> 106]]> <![CDATA[<211> 2536]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 106]]> agctctcaga gggaattgag cacccggcag cggtctcagg ccaagccccc tgccagcatg 60 gccagcgagt tcaagaagaa gctcttctgg agggcagtgg tggccgagtt cctggccacg 120 accctctttg tcttcatcag catcggttct gccctgggct tcaaataccc ggtggggaac 180 aaccagacgg cggtccagga caacgtgaag gtgtcgctgg ccttcgggct gagcatcgcc 240 acgctggcgc agagtgtggg ccacatcagc ggcgcccacc tcaacccggc tgtcacactg 300 gggctgctgc tcagctgcca gatcagcatc ttccgtgccc tcatgtacat catcgcccag 360 tgcgtggggg ccatcgtcgc caccgccatc ctctcaggca tcacctcctc cctgactggg 420 aactcgcttg gccgcaatga cctggctgat ggtgtgaact cgggccaggg cctgggcatc 480 gagatcatcg ggaccctcca gctggtgcta tgcgtgctgg ctactaccga ccggaggcgc 540 cgtgaccttg gtggctcagc cccccttgcc atcggcctct ctgtagccct tggacacctc 600 ctggctattg actacactgg ctgtgggatt aaccctgctc ggtcctttgg ctccgcggtg 660 atcacacaca acttcagcaa ccactggatt ttctgggtgg ggccattcat cgggggagcc 720 ctggctgtac tcatctacga cttcatcctg gccccacgca gcagtgacct cacagaccgc 780 gtgaaggtgt ggaccagcgg ccaggtggag gagtatgacc tggatgccga cgacatcaac 840 tccaggagct tcctggggac caagatttac caattcaccc actcccttga agttgtggag 900 gaggtgaaag aaagggaccc acctgctagt cgcccctcag agcatgatgg gaggtgtgcc 960 agaaagtccc ccctcgcccc aaagttgctc accgactcac ctgcgcaagt gcctgggatt 1020 ctaccgtaat tgctttgtgc ctttgggcac ggccctcctt cttttcctaa catgcacctt 1080 gctcccaatg gtgcttggag ggggaagaga tcccaggagg tgcagtggag ggggcaagct 1140 ttgctccttc agttctgctt gctcccaagc ccctgacccg ctcggactta ctgcctgacc 1200 ttggaatcgt ccctatatca gggcctgagt gacctccttc tgcaaagtgg cagggaccgg 1260 cagagctcta caggcctgca gcccctaagt gcaaacacag catgggtcca gaagacgtgg 1320 tctagaccag ggctgctctt tccacttgcc ctgtgttctt tccccagggg catgactgtc 1380 gccacacgcc tctgtgtaca tgtgtgcaga gcagacaggc tacaaagcag agatcgacag 1440 acagccaggt agttggaact ttctgttccc tatggagagg cttccctaca cagggcctgc 1500 tattgcagaa tgaagccatt tagagggtga aggagaaata cccatgttac ttctctgagt 1560 tttagttggt ctttccatct atcactgcat tatcttgctc attcttcagt tctctactcc 1620 ctcttgtcag tgtagacaca ggtcaccatt atgctggtgt atgtttatca aagagcactt 1680 gagctgtctg aagcccaaag cctgaggaca gaaagaccct gatgcaggtc agcccatgga 1740 ggcagatgcc cttgctgggc ctgggggttt tccaagccct cagctggtcc tgaccaggat 1800 ggagcaagct cttcccttgc tcatgagctc ctgatcagag gcatttgagc agctgaataa 1860 cctgcacagg cttgctgtat gacccctggc cacagccttc cctctgcatt gacctggagg 1920 ggagaggtca gccttgacct aatgaggtag ctatagttgc agcccaagga cagttcagag 1980 atcaggatca gctttgaagg ctggattcta tctacataag tcctttcaat tccaccaggg 2040 ccagagcagc tccaccactg tgcacttagc catgatggca acagaaacca agagacacaa 2100 ttacgcaggt atttagaagc agagggacaa ccagaaggcc cttaactatc accagtgcat 2160 cacatctgca cactctcttc tccattccct agcaggaact tctagctcat ttaacagata 2220 aagaaactga ggcccacggt ttcagctaga caatgatttg gccaggccta gtaaccaagg 2280 ccctgtctct ggctactccc tggaccacga ggctgattcc tctcatttcc agcttctcag 2340 tttctgcctg ggcaatggcc aggggccagg agtggggaga gttgtgatgg aggggagagg 2400 ggtcacaccc accccctgcc tggttctagg ctgctgcaca ccaaggccct gcatctgtct 2460 gctctgcata tatgtctctt tggagttgga atttcattat atgttaagaa aataaaggaa 2520 aatgacttgt aaggtc 2536 <![CDATA[<210> 107]]> <![CDATA[<211> 2754]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 107]]> agctctcaga gggaattgag cacccggcag cggtctcagg ccaagccccc tgccagcatg 60 gccagcgagt tcaagaagaa gctcttctgg agggcagtgg tggccgagtt cctggccacg 120 accctctttg tcttcatcag catcggttct gccctgggct tcaaataccc ggtggggaac 180 aaccagacgg cggtccagga caacgtgaag gtgtcgctgg ccttcgggct gagcatcgcc 240 acgctggcgc agagtgtggg ccacatcagc ggcgcccacc tcaacccggc tgtcacactg 300 gggctgctgc tcagctgcca gatcagcatc ttccgtgccc tcatgtacat catcgcccag 360 tgcgtggggg ccatcgtcgc caccgccatc ctctcaggca tcacctcctc cctgactggg 420 aactcgcttg gccgcaatga cctggctgat ggtgtgaact cgggccaggg cctgggcatc 480 gagatcatcg ggaccctcca gctggtgcta tgcgtgctgg ctactaccga ccggaggcgc 540 cgtgaccttg gtggctcagc cccccttgcc atcggcctct ctgtagccct tggacacctc 600 ctggctattg actacactgg ctgtgggatt aaccctgctc ggtcctttgg ctccgcggtg 660 atcacacaca acttcagcaa ccactggatt ttctgggtgg ggccattcat cgggggagcc 720 ctggctgtac tcatctacga cttcatcctg gccccacgca gcagtgacct cacagaccgc 780 gtgaaggtgt ggaccagcgg ccaggtggag gagtatgacc tggatgccga cgacatcaac 840 tccagggtgg agatgaagcc caaatagaag gggtctggcc cgggcatcca cgtagggggc 900 aggggcaggg gcgggcggag ggaggggagg ggtgaaatcc atactgtaga cactctgaca 960 agctggccaa agtcacttcc ccaagatctg ccagacctgc atggtcaagc ctcttatggg 1020 ggtgtttcta tctctttctt tctctttctg tttcctggcc tcagagcttc ctggggacca 1080 agatttacca attcacccac tcccttgaag ttgtggagga ggtgaaagaa agggacccac 1140 ctgctagtcg cccctcagag catgatggga ggtgtgccag aaagtccccc ctcgccccaa 1200 agttgctcac cgactcacct gcgcaagtgc ctgggattct accgtaattg ctttgtgcct 1260 ttgggcacgg ccctccttct tttcctaaca tgcaccttgc tcccaatggt gcttggaggg 1320 ggaagagatc ccaggaggtg cagtggaggg ggcaagcttt gctccttcag ttctgcttgc 1380 tcccaagccc ctgacccgct cggacttact gcctgacctt ggaatcgtcc ctatatcagg 1440 gcctgagtga cctccttctg caaagtggca gggaccggca gagctctaca ggcctgcagc 1500 ccctaagtgc aaacacagca tgggtccaga agacgtggtc tagaccaggg ctgctctttc 1560 cacttgccct gtgttctttc cccaggggca tgactgtcgc cacacgcctc tgtgtacatg 1620 tgtgcagagc agacaggcta caaagcagag atcgacagac agccaggtag ttggaacttt 1680 ctgttcccta tggagaggct tccctacaca gggcctgcta ttgcagaatg aagccattta 1740 gagggtgaag gagaaatacc catgttactt ctctgagttt tagttggtct ttccatctat 1800 cactgcatta tcttgctcat tcttcagttc tctactccct cttgtcagtg tagacacagg 1860 tcaccattat gctggtgtat gtttatcaaa gagcacttga gctgtctgaa gcccaaagcc 1920 tgaggacaga aagaccctga tgcaggtcag cccatggagg cagatgccct tgctgggcct 1980 gggggttttc caagccctca gctggtcctg accaggatgg agcaagctct tcccttgctc 2040 atgagctcct gatcagaggc atttgagcag ctgaataacc tgcacaggct tgctgtatga 2100 cccctggcca cagccttccc tctgcattga cctggagggg agaggtcagc cttgacctaa 2160 tgaggtagct atagttgcag cccaaggaca gttcagagat caggatcagc tttgaaggct 2220 ggattctatc tacataagtc ctttcaattc caccagggcc agagcagctc caccactgtg 2280 cacttagcca tgatggcaac agaaaccaag agacacaatt acgcaggtat ttagaagcag 2340 agggacaacc agaaggccct taactatcac cagtgcatca catctgcaca ctctcttctc 2400 cattccctag caggaacttc tagctcattt aacagataaa gaaactgagg cccacggttt 2460 cagctagaca atgatttggc caggcctagt aaccaaggcc ctgtctctgg ctactccctg 2520 gaccacgagg ctgattcctc tcatttccag cttctcagtt tctgcctggg caatggccag 2580 gggccaggag tggggagagt tgtgatggag gggagagggg tcacacccac cccctgcctg 2640 gttctaggct gctgcacacc aaggccctgc atctgtctgc tctgcatata tgtctctttg 2700 gagttggaat ttcattatat gttaagaaaa taaaggaaaa tgacttgtaa ggtc 2754 <![CDATA[<210> 108]]> <![CDATA[<211> 3670]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 108]]> ggagctgcgg cggggtctgg ggcgcagagc agcggcggga ggaggcggac acgtggcaac 60 agcggtagca gcccgggcgg cggcagcaac agcggcggcg gcatcggccc gagccgccgg 120 ccgccctccc accctcccgc cccgcggcag ccctagctcc ctccacttgg ctcccctggt 180 cccgctcgct cggccgggag ctgctctgtg cttttctctc tgattctcca gcgacaggac 240 ccggcgccgg gcactgagca ccgccaccat ggggaagggg gttggacgtg ataagtatga 300 gcctgcagct gtttcagaac aaggtgataa aaagggcaaa aagggcaaaa aagacaggga 360 catggatgaa ctgaagaaag aagtttctat ggatgatcat aaacttagcc ttgatgaact 420 tcatcgtaaa tatggaacag acttgagccg gggattaaca tctgctcgtg cagctgagat 480 cctggcgcga gatggtccca acgccctcac tccccctccc actactcctg aatggatcaa 540 gttttgtcgg cagctctttg gggggttctc aatgttactg tggattggag cgattctttg 600 tttcttggct tatagcatcc aagctgctac agaagaggaa cctcaaaacg ataatctgta 660 cctgggtgtg gtgctatcag ccgttgtaat cataactggt tgcttctcct actatcaaga 720 agctaaaagt tcaaagatca tggaatcctt caaaaacatg gtccctcagc aagcccttgt 780 gattcgaaat ggtgagaaaa tgagcataaa tgcggaggaa gttgtggttg gggatctggt 840 ggaagtaaaa ggaggagacc gaattcctgc tgacctcaga atcatatctg caaatggctg 900 caaggtggat aactcctcgc tcactggtga atcagaaccc cagactaggt ctccagattt 960 cacaaatgaa aaccccctgg agacgaggaa cattgccttc ttttcaacca attgtgttga 1020 aggcaccgca cgtggtattg ttgtctacac tggggatcgc actgtgatgg gaagaattgc 1080 cacacttgct tctgggctgg aaggaggcca gacccccatt gctgcagaaa ttgaacattt 1140 tatccacatc atcacgggtg tggctgtgtt cctgggtgtg tctttcttca tcctttctct 1200 catccttgag tacacctggc ttgaggctgt catcttcctc atcggtatca tcgtagccaa 1260 tgtgccggaa ggtttgctgg ccactgtcac ggtctgtctg acacttactg ccaaacgcat 1320 ggcaaggaaa aactgcttag tgaagaactt agaagctgtg gagaccttgg ggtccacgtc 1380 caccatctgc tctgataaaa ctggaactct gactcagaac cggatgacag tggcccacat 1440 gtggtttgac aatcaaatcc atgaagctga tacgacagag aatcagagtg gtgtctcttt 1500 tgacaagact tcagctacct ggcttgctct gtccagaatt gcaggtcttt gtaacagggc 1560 agtgtttcag gctaaccagg aaaacctacc tattcttaag cgggcagttg caggagatgc 1620 ctctgagtca gcactcttaa agtgcataga gctgtgctgt ggttccgtga aggagatgag 1680 agaaagatac gccaaaatcg tcgagatacc cttcaactcc accaacaagt accagttgtc 1740 tattcataag aaccccaaca catcggagcc ccaacacctg ttggtgatga agggcgcccc 1800 agaaaggatc ctagaccgtt gcagctctat cctcctccac ggcaaggagc agcccctgga 1860 tgaggagctg aaagacgcct ttcagaacgc ctatttggag ctggggggcc tcggagaacg 1920 agtcctaggt ttctgccacc tctttctgcc agatgaacag tttcctgaag ggttccagtt 1980 tgacactgac gatgtgaatt tccctatcga taatctgtgc tttgttgggc tcatctccat 2040 gattgaccct ccacgggcgg ccgttcctga tgccgtgggc aaatgtcgaa gtgctggaat 2100 taaggtcatc atggtcacag gagaccatcc aatcacagct aaagctattg ccaaaggtgt 2160 gggcatcatc tcagaaggca atgagaccgt ggaagacatt gctgcccgcc tcaacatccc 2220 agtcagccag gtgaacccca gggatgccaa ggcctgcgta gtacacggca gtgatctaaa 2280 ggacatgacc tccgagcagc tggatgacat tttgaagtac cacactgaga tagtgtttgc 2340 caggacctcc cctcagcaga agctcatcat tgtggaaggc tgccaaagac agggtgctat 2400 cgtggctgtg actggtgacg gtgtgaatga ctctccagct ttgaagaaag cagacattgg 2460 ggttgctatg gggattgctg gctcagatgt gtccaagcaa gctgctgaca tgattcttct 2520 ggatgacaac tttgcctcaa ttgtgactgg agtagaggaa ggtcgtctga tctttgataa 2580 cttgaagaaa tccattgctt ataccttaac cagtaacatt cccgagatca ccccgttcct 2640 gatatttatt attgcaaaca ttccactacc actggggact gtcaccatcc tctgcattga 2700 cttgggcact gacatggttc ctgccatctc cctggcttat gagcaggctg agagtgacat 2760 catgaagaga cagcccagaa atcccaaaac agacaaactt gtgaatgagc ggctgatcag 2820 catggcctat gggcagattg gaatgatcca ggccctggga ggcttcttta cttactttgt 2880 gattctggct gagaacggct tcctcccaat tcacctgttg ggcctccgag tggactggga 2940 tgaccgctgg atcaacgatg tggaagacag ctacgggcag cagtggacct atgagcagag 3000 gaaaatcgtg gagttcacct gccacacagc cttcttcgtc agtatcgtgg tggtgcagtg 3060 ggccgacttg gtcatctgta agaccaggag gaattcggtc ttccagcagg ggatgaagaa 3120 caagatcttg atatttggcc tctttgaaga gacagccctg gctgctttcc tttcctactg 3180 ccctggaatg ggtgttgctc ttaggatgta tcccctcaaa cctacctggt ggttctgtgc 3240 cttcccctac tctcttctca tcttcgtata tgacgaagtc agaaaactca tcatcaggcg 3300 acgccctggc ggctgggtgg agaaggaaac ctactattag ccccccgtcc tgcacgccgt 3360 ggagcatcag gccacacact ctgcatccga cacccacccc ctctttgtgt acttcagtct 3420 tggagtttgg aactctaccc tggtaggaaa gcaccgcagc atgtggggaa gcaagacgtc 3480 ctggaatgaa gcatgtagct ctatgggggg aggggggagg gctgcctgaa aaccatccat 3540 ctgtggaaat gacagcgggg aaggttttta tgtgcctttt tgtttttgta aaaaaggaac 3600 acccggaaag actgaaagaa tacattttat atctggattt ttacaaataa agatggctat 3660 tataatggaa 3670 <![CDATA[<210> 109]]> <![CDATA[<211> 3765]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 109]]> agcagcgggg gcggccccgg gactgagccg gcatccctga gcctggctcc cctccctgcg 60 accgccgtca cctccttctc cttccttttc cctccgccct ccgtgccctg aggaaaggcg 120 cgctcctccc cttcccctgg ggcgctccgc cggggcctcc tcccgggcct ccgttcccgc 180 cgcggccccg gttccggcgg gggcagcctc cgggttcggg gctccttctc ctggggacgc 240 tggggcttag cttgctccgc gcagaggcgg ccgccctccc ccaaagaaaa aactggctgc 300 ttctaagtgc gaagccggct gggcgggctg gtgccagaaa gggtgtgtct tcactgccct 360 aagatggcct ttaaggttgg acgtgataag tatgagcctg cagctgtttc agaacaaggt 420 gataaaaagg gcaaaaaggg caaaaaagac agggacatgg atgaactgaa gaaagaagtt 480 tctatggatg atcataaact tagccttgat gaacttcatc gtaaatatgg aacagacttg 540 agccggggat taacatctgc tcgtgcagct gagatcctgg cgcgagatgg tcccaacgcc 600 ctcactcccc ctcccactac tcctgaatgg atcaagtttt gtcggcagct ctttgggggg 660 ttctcaatgt tactgtggat tggagcgatt ctttgtttct tggcttatag catccaagct 720 gctacagaag aggaacctca aaacgataat ctgtacctgg gtgtggtgct atcagccgtt 780 gtaatcataa ctggttgctt ctcctactat caagaagcta aaagttcaaa gatcatggaa 840 tccttcaaaa acatggtccc tcagcaagcc cttgtgattc gaaatggtga gaaaatgagc 900 ataaatgcgg aggaagttgt ggttggggat ctggtggaag taaaaggagg agaccgaatt 960 cctgctgacc tcagaatcat atctgcaaat ggctgcaagg tggataactc ctcgctcact 1020 ggtgaatcag aaccccagac taggtctcca gatttcacaa atgaaaaccc cctggagacg 1080 aggaacattg ccttcttttc aaccaattgt gttgaaggca ccgcacgtgg tattgttgtc 1140 tacactgggg atcgcactgt gatgggaaga attgccacac ttgcttctgg gctggaagga 1200 ggccagaccc ccattgctgc agaaattgaa cattttatcc acatcatcac gggtgtggct 1260 gtgttcctgg gtgtgtcttt cttcatcctt tctctcatcc ttgagtacac ctggcttgag 1320 gctgtcatct tcctcatcgg tatcatcgta gccaatgtgc cggaaggttt gctggccact 1380 gtcacggtct gtctgacact tactgccaaa cgcatggcaa ggaaaaactg cttagtgaag 1440 aacttagaag ctgtggagac cttggggtcc acgtccacca tctgctctga taaaactgga 1500 actctgactc agaaccggat gacagtggcc cacatgtggt ttgacaatca aatccatgaa 1560 gctgatacga cagagaatca gagtggtgtc tcttttgaca agacttcagc tacctggctt 1620 gctctgtcca gaattgcagg tctttgtaac agggcagtgt ttcaggctaa ccaggaaaac 1680 ctacctattc ttaagcgggc agttgcagga gatgcctctg agtcagcact cttaaagtgc 1740 atagagctgt gctgtggttc cgtgaaggag atgagagaaa gatacgccaa aatcgtcgag 1800 atacccttca actccaccaa caagtaccag ttgtctattc ataagaaccc caacacatcg 1860 gagccccaac acctgttggt gatgaagggc gccccagaaa ggatcctaga ccgttgcagc 1920 tctatcctcc tccacggcaa ggagcagccc ctggatgagg agctgaaaga cgcctttcag 1980 aacgcctatt tggagctggg gggcctcgga gaacgagtcc taggtttctg ccacctcttt 2040 ctgccagatg aacagtttcc tgaagggttc cagtttgaca ctgacgatgt gaatttccct 2100 atcgataatc tgtgctttgt tgggctcatc tccatgattg accctccacg ggcggccgtt 2160 cctgatgccg tgggcaaatg tcgaagtgct ggaattaagg tcatcatggt cacaggagac 2220 catccaatca cagctaaagc tattgccaaa ggtgtgggca tcatctcaga aggcaatgag 2280 accgtggaag acattgctgc ccgcctcaac atcccagtca gccaggtgaa ccccagggat 2340 gccaaggcct gcgtagtaca cggcagtgat ctaaaggaca tgacctccga gcagctggat 2400 gacattttga agtaccacac tgagatagtg tttgccagga cctcccctca gcagaagctc 2460 atcattgtgg aaggctgcca aagacagggt gctatcgtgg ctgtgactgg tgacggtgtg 2520 aatgactctc cagctttgaa gaaagcagac attggggttg ctatggggat tgctggctca 2580 gatgtgtcca agcaagctgc tgacatgatt cttctggatg acaactttgc ctcaattgtg 2640 actggagtag aggaaggtcg tctgatcttt gataacttga agaaatccat tgcttatacc 2700 ttaaccagta acattcccga gatcaccccg ttcctgatat ttattattgc aaacattcca 2760 ctaccactgg ggactgtcac catcctctgc attgacttgg gcactgacat ggttcctgcc 2820 atctccctgg cttatgagca ggctgagagt gacatcatga agagacagcc cagaaatccc 2880 aaaacagaca aacttgtgaa tgagcggctg atcagcatgg cctatgggca gattggaatg 2940 atccaggccc tgggaggctt ctttacttac tttgtgattc tggctgagaa cggcttcctc 3000 ccaattcacc tgttgggcct ccgagtggac tgggatgacc gctggatcaa cgatgtggaa 3060 gacagctacg ggcagcagtg gacctatgag cagaggaaaa tcgtggagtt cacctgccac 3120 acagccttct tcgtcagtat cgtggtggtg cagtgggccg acttggtcat ctgtaagacc 3180 aggaggaatt cggtcttcca gcaggggatg aagaacaaga tcttgatatt tggcctcttt 3240 gaagagacag ccctggctgc tttcctttcc tactgccctg gaatgggtgt tgctcttagg 3300 atgtatcccc tcaaacctac ctggtggttc tgtgccttcc cctactctct tctcatcttc 3360 gtatatgacg aagtcagaaa actcatcatc aggcgacgcc ctggcggctg ggtggagaag 3420 gaaacctact attagccccc cgtcctgcac gccgtggagc atcaggccac acactctgca 3480 tccgacaccc accccctctt tgtgtacttc agtcttggag tttggaactc taccctggta 3540 ggaaagcacc gcagcatgtg gggaagcaag acgtcctgga atgaagcatg tagctctatg 3600 gggggagggg ggagggctgc ctgaaaacca tccatctgtg gaaatgacag cggggaaggt 3660 ttttatgtgc ctttttgttt ttgtaaaaaa ggaacacccg gaaagactga aagaatacat 3720 tttatatctg gatttttaca aataaagatg gctattataa tggaa 3765 <![CDATA[<210> 110]]> <![CDATA[<211> 3574]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 110]]> gatatgtaat aatgtctttg caaagcaaag aatataaaca gtataaaagt actagcattt 60 agatgtattg tatcatttaa tccttaaaaa catgaaatga ggttggcact attctttatc 120 tccacgctgt ggaagaggaa attgaaatgt agaagttagt aacttgccta aggatacact 180 gctggttgga cgtgataagt atgagcctgc agctgtttca gaacaaggtg ataaaaaggg 240 caaaaagggc aaaaaagaca gggacatgga tgaactgaag aaagaagttt ctatggatga 300 tcataaactt agccttgatg aacttcatcg taaatatgga acagacttga gccggggatt 360 aacatctgct cgtgcagctg agatcctggc gcgagatggt cccaacgccc tcactccccc 420 tcccactact cctgaatgga tcaagttttg tcggcagctc tttggggggt tctcaatgtt 480 actgtggatt ggagcgattc tttgtttctt ggcttatagc atccaagctg ctacagaaga 540 ggaacctcaa aacgataatc tgtacctggg tgtggtgcta tcagccgttg taatcataac 600 tggttgcttc tcctactatc aagaagctaa aagttcaaag atcatggaat ccttcaaaaa 660 catggtccct cagcaagccc ttgtgattcg aaatggtgag aaaatgagca taaatgcgga 720 ggaagttgtg gttggggatc tggtggaagt aaaaggagga gaccgaattc ctgctgacct 780 cagaatcata tctgcaaatg gctgcaaggt ggataactcc tcgctcactg gtgaatcaga 840 accccagact aggtctccag atttcacaaa tgaaaacccc ctggagacga ggaacattgc 900 cttcttttca accaattgtg ttgaaggcac cgcacgtggt attgttgtct acactgggga 960 tcgcactgtg atgggaagaa ttgccacact tgcttctggg ctggaaggag gccagacccc 1020 cattgctgca gaaattgaac attttatcca catcatcacg ggtgtggctg tgttcctggg 1080 tgtgtctttc ttcatccttt ctctcatcct tgagtacacc tggcttgagg ctgtcatctt 1140 cctcatcggt atcatcgtag ccaatgtgcc ggaaggtttg ctggccactg tcacggtctg 1200 tctgacactt actgccaaac gcatggcaag gaaaaactgc ttagtgaaga acttagaagc 1260 tgtggagacc ttggggtcca cgtccaccat ctgctctgat aaaactggaa ctctgactca 1320 gaaccggatg acagtggccc acatgtggtt tgacaatcaa atccatgaag ctgatacgac 1380 agagaatcag agtggtgtct cttttgacaa gacttcagct acctggcttg ctctgtccag 1440 aattgcaggt ctttgtaaca gggcagtgtt tcaggctaac caggaaaacc tacctattct 1500 taagcgggca gttgcaggag atgcctctga gtcagcactc ttaaagtgca tagagctgtg 1560 ctgtggttcc gtgaaggaga tgagagaaag atacgccaaa atcgtcgaga tacccttcaa 1620 ctccaccaac aagtaccagt tgtctattca taagaacccc aacacatcgg agccccaaca 1680 cctgttggtg atgaagggcg ccccagaaag gatcctagac cgttgcagct ctatcctcct 1740 ccacggcaag gagcagcccc tggatgagga gctgaaagac gcctttcaga acgcctattt 1800 ggagctgggg ggcctcggag aacgagtcct aggtttctgc cacctctttc tgccagatga 1860 acagtttcct gaagggttcc agtttgacac tgacgatgtg aatttcccta tcgataatct 1920 gtgctttgtt gggctcatct ccatgattga ccctccacgg gcggccgttc ctgatgccgt 1980 gggcaaatgt cgaagtgctg gaattaaggt catcatggtc acaggagacc atccaatcac 2040 agctaaagct attgccaaag gtgtgggcat catctcagaa ggcaatgaga ccgtggaaga 2100 cattgctgcc cgcctcaaca tcccagtcag ccaggtgaac cccagggatg ccaaggcctg 2160 cgtagtacac ggcagtgatc taaaggacat gacctccgag cagctggatg acattttgaa 2220 gtaccacact gagatagtgt ttgccaggac ctcccctcag cagaagctca tcattgtgga 2280 aggctgccaa agacagggtg ctatcgtggc tgtgactggt gacggtgtga atgactctcc 2340 agctttgaag aaagcagaca ttggggttgc tatggggatt gctggctcag atgtgtccaa 2400 gcaagctgct gacatgattc ttctggatga caactttgcc tcaattgtga ctggagtaga 2460 ggaaggtcgt ctgatctttg ataacttgaa gaaatccatt gcttatacct taaccagtaa 2520 cattcccgag atcaccccgt tcctgatatt tattattgca aacattccac taccactggg 2580 gactgtcacc atcctctgca ttgacttggg cactgacatg gttcctgcca tctccctggc 2640 ttatgagcag gctgagagtg acatcatgaa gagacagccc agaaatccca aaacagacaa 2700 acttgtgaat gagcggctga tcagcatggc ctatgggcag attggaatga tccaggccct 2760 gggaggcttc tttacttact ttgtgattct ggctgagaac ggcttcctcc caattcacct 2820 gttgggcctc cgagtggact gggatgaccg ctggatcaac gatgtggaag acagctacgg 2880 gcagcagtgg acctatgagc agaggaaaat cgtggagttc acctgccaca cagccttctt 2940 cgtcagtatc gtggtggtgc agtgggccga cttggtcatc tgtaagacca ggaggaattc 3000 ggtcttccag caggggatga agaacaagat cttgatattt ggcctctttg aagagacagc 3060 cctggctgct ttcctttcct actgccctgg aatgggtgtt gctcttagga tgtatcccct 3120 caaacctacc tggtggttct gtgccttccc ctactctctt ctcatcttcg tatatgacga 3180 agtcagaaaa ctcatcatca ggcgacgccc tggcggctgg gtggagaagg aaacctacta 3240 ttagcccccc gtcctgcacg ccgtggagca tcaggccaca cactctgcat ccgacaccca 3300 ccccctcttt gtgtacttca gtcttggagt ttggaactct accctggtag gaaagcaccg 3360 cagcatgtgg ggaagcaaga cgtcctggaa tgaagcatgt agctctatgg ggggaggggg 3420 gagggctgcc tgaaaaccat ccatctgtgg aaatgacagc ggggaaggtt tttatgtgcc 3480 tttttgtttt tgtaaaaaag gaacacccgg aaagactgaa agaatacatt ttatatctgg 3540 atttttacaa ataaagatgg ctattataat ggaa 3574 <![CDATA[<210> 111]]> <![CDATA[<211> 8024]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 111]]> gccgccgggc cacggcctgc aggggtggaa ggggcggcgg cggcgggagc tgcgggccac 60 gcacggcggc ggcggcggga gcggccgggc acgcacggcg acggcggcgg cgggagcggg 120 agcccgggcc acgcacggcc gcagctgcgg gtgcggcggg cgcgggagcg gtgggagctg 180 tggtggcggc ggatggccca gagctgatct atgcggcgcc tggaggggct gtgtctgcgg 240 cggcggcgga ggcggcgggg ccctgcccgc gagcggagcg gggacaagat gaagtaccag 300 aaatacctga cggtgctgca gatggccatc ggcgtcaccc cctccaaccg cggcagcctc 360 ctgccgctca agaggaagct gtgggtaacg ccatcctctg aaaatcctaa tggtgctact 420 tctagtgtca gccaaggaaa accctcttta agacgaatta aagggagatt acacagaagc 480 aaaagccttg atagcatgga tttctgtgag ctcactagca cagcaatgga ggaaacagct 540 atatgggaac aacatacagt gacgcttcac agggctcctg gatttggatt tggaattgca 600 atatctggtg gacgagataa tcctcatttt cagagtgggg aaacgtcaat agtgatttca 660 gatgtgctga aaggaggacc agctgaagga cagctacagg aaaatgaccg agttgcaatg 720 gttaacggag tttcaatgga taatgttgaa catgcttttg ctgttcagca actaaggaaa 780 agtgggaaaa atgcaaaaat tacaattaga aggaagaaga aagttcaaat accagtaagt 840 cgtcctgatc ctgaaccagt atctgataat gaagaagata gttatgatga ggaaatacat 900 gatccaagaa gtggccggag tggtgtggtt aacagaagga gtgagaagat ttggccgagg 960 gatagaagtg caagtagaga gaggagcttg tccccgcggt cagacaggcg gtcagtggct 1020 tccagccagc ctgctaaacc tactaaagtc acactggtga aatcccggaa aaatgaagaa 1080 tatggtcttc gattggcaag ccatatattt gttaaggaaa tttcacaaga tagtttggca 1140 gcaagagatg gcaatattca agaaggtgat gttgtattga agataaatgg tactgtgaca 1200 gaaaatatgt cattgacaga tgcaaagaca ttgatagaaa ggtctaaagg caaattaaaa 1260 atggtagttc aaagagatga acgggctacg ctattgaatg tccctgatct ttctgacagc 1320 atccactctg ctaatgcctc tgagagagac gacatttcag aaattcagtc actggcatca 1380 gatcattctg gtcgatcaca cgataggcct ccccgccgca gccggtcacg atctcctgac 1440 cagcggtcag agccttctga tcattccagg cactcgccgc agcagccaag caatggcagt 1500 ctccggagta gagatgaaga gagaatttct aaacctgggg ctgtctcaac tcctgtaaag 1560 catgctgatg atcacacacc taaaacagtg gaagaagtta cagttgaaag aaatgagaaa 1620 caaacacctt ctcttccaga accaaagcct gtgtatgccc aagttgggca accagatgtg 1680 gatttacctg tcagtccatc tgatggtgtc ctacctaatt caactcatga agatgggatt 1740 cttcggccca gcatgaaatt ggtaaaattc agaaaaggag atagtgtggg tttgcggctg 1800 gctggtggaa atgatgttgg aatatttgta gctggcgttc tagaagatag ccctgcagcc 1860 aaggaaggct tagaggaagg tgatcaaatt ctcagggtaa acaacgtaga ttttacaaat 1920 atcataagag aagaagccgt ccttttcctg cttgacctcc ctaaaggaga agaagtgacc 1980 atattggctc agaagaagaa ggatgtttat cgtcgcattg tagaatcaga tgtaggagat 2040 tctttctata ttagaaccca ttttgaatat gaaaaggaat ctccctatgg acttagtttt 2100 aacaaaggag aggtgttccg tgttgtggat accttgtaca atggaaaact gggctcttgg 2160 cttgctattc gaattggtaa aaatcataag gaggtagaac gaggcatcat ccctaataag 2220 aacagagctg agcagctagc cagtgtacag tatacacttc caaaaacagc aggcggagac 2280 cgtgctgact tctggagatt cagaggtctt cgcagctcca agagaaatct tcgaaaaagc 2340 agagaggatt tgtccgctca gcctgttcaa acaaagtttc cagcttatga aagagtggtt 2400 cttcgagaag ctggatttct gaggcctgta accatttttg gaccaatagc tgatgttgcc 2460 agagaaaagc tggcaagaga agaaccagat atttatcaaa ttgcaaagag tgaaccacga 2520 gacgctggaa ctgaccaacg tagctctggc attattcgcc tgcatacaat aaagcaaatc 2580 atagatcaag acaaacatgc tttattagat gtaacaccaa atgcagttga tcgtcttaac 2640 tatgcccagt ggtatccaat tgttgtattt cttaaccctg attctaagca aggagtaaaa 2700 acaatgagaa tgaggttatg tccagaatct cggaaaagtg ccaggaagtt atacgagcga 2760 tctcataaac ttcgtaaaaa taatcaccat ctttttacaa ctacaattaa cttaaattca 2820 atgaatgatg gttggtatgg tgcgctgaaa gaagcaattc aacaacagca aaaccagctg 2880 gtatgggttt ccgagggaaa ggcggatggt gctacaagtg atgaccttga tttgcatgat 2940 gatcgtctgt cctacctgtc agctccaggt agtgaatact caatgtatag cacggacagt 3000 agacacactt ctgactatga agacacagac acagaaggcg gggcctacac tgatcaagaa 3060 ctagatgaaa ctcttaatga tgaggttggg actccaccgg agtctgccat tacacggtcc 3120 tctgagcctg taagagagga ctcctctgga atgcatcatg aaaaccaaac atatcctcct 3180 tactcaccac aagcgcagcc acaaccaatt catagaatag actcccctgg atttaagcca 3240 gcctctcaac agaaagcaga agcttcatct ccagtccctt acctttcgcc tgaaacaaac 3300 ccagcatcat caacctctgc tgttaatcat aatgtaaatt taactaatgt cagactggag 3360 gagcccaccc cagctccttc cacctcttac tcaccacaag ctgattcttt aagaacacca 3420 agtactgagg cagctcacat aatgctaaga gatcaagaac catcattgtc gtcgcatgta 3480 gatccaacaa aggtgtatag aaaggatcca tatcccgagg aaatgatgag gcagaaccat 3540 gttttgaaac agccagccgt tagtcaccca gggcacaggc cagacaaaga gcctaatctg 3600 acctatgaac cccaactccc atacgtagag aaacaagcca gcagagacct cgagcagccc 3660 acatacagat acgagtcctc aagctatacg gaccagtttt ctcgaaacta tgaacatcgt 3720 ctgcgatacg aagatcgcgt ccccatgtat gaagaacagt ggtcatatta tgatgacaaa 3780 cagccctacc catctcggcc accttttgat aatcagcact ctcaagacct tgactccaga 3840 cagcatcccg aagagtcctc agaacgaggg tactttccac gttttgaaga gccagcccct 3900 ctgtcttacg acagcagacc acgttacgaa caggcaccta gagcatccgc cctgcggcac 3960 gaagagcagc cagctcctgg gtatgacaca catggtagac tcagaccgga agcccagccc 4020 cacccttcag cagggcccaa gcctgcagag tccaagcagt attttgagca atattcacgc 4080 agttacgagc aagtaccacc ccaaggattt acctctagag caggtcattt tgagcctctc 4140 catggtgctg cagctgtccc tccgctgata ccttcatctc agcataagcc agaagctctg 4200 ccttcaaaca ccaaaccact gcctccaccc ccaactcaaa ccgaagaaga ggaagatcca 4260 gcaatgaagc cacagtctgt actcaccaga gttaagatgt ttgaaaacaa aagatctgca 4320 tccttagaga ccaagaagga tgtaaatgac actggcagtt ttaagcctcc agaagtagca 4380 tctaaacctt caggtgctcc catcattggt cccaaaccca cttctcagaa tcaattcagt 4440 gaacatgaca aaactctgta caggatccca gaacctcaaa aacctcaact gaagccacct 4500 gaagatattg ttcggtccaa tcattatgac cctgaagaag atgaagaata ttatcgaaaa 4560 cagctgtcat actttgaccg aagaagtttt gagaataagc ctcctgcaca cattgccgcc 4620 agccatctct ccgagcctgc aaagccagcg cattctcaga atcaatcaaa tttttctagt 4680 tattcttcaa agggaaagcc tcctgaagct gatggtgtgg atagatcatt tggcgagaaa 4740 cgctatgaac ccatccaggc cactccccct cctcctccat tgccctcgca gtatgcccag 4800 ccatctcagc ctgtcaccag cgcgtctctc cacatacatt ctaagggagc acatggtgaa 4860 ggtaattcag tgtcattgga ttttcagaat tccttagtgt ccaaaccaga cccacctcca 4920 tctcagaata agccagcaac tttcagacca ccaaaccgag aagatactgc tcaggcagct 4980 ttctatcccc agaaaagttt tccagataaa gccccagtta atggaactga acagactcag 5040 aaaacagtca ctccagcata caatcgattc acaccaaaac catatacaag ttctgcccga 5100 ccatttgaac gcaagtttga aagtcctaaa ttcaatcaca atcttctgcc aagtgaaact 5160 gcacataaac ctgacttgtc ttcaaaaact cccacttctc caaaaactct tgtgaaatcg 5220 cacagtttgg cacagcctcc tgagtttgac agtggagttg aaactttctc tatccatgca 5280 gagaagccta aatatcaaat aaataatatc agcacagtgc ctaaagctat tcctgtgagt 5340 ccttcagctg tggaagagga tgaagatgaa gatggtcata ctgtggtggc cacagcccga 5400 ggcatattta acagcaatgg gggcgtgctg agttccatag aaactggtgt tagtataatt 5460 atccctcaag gagccattcc cgaaggagtt gagcaggaaa tctatttcaa ggtctgccgg 5520 gacaacagca tccttccacc tttagataaa gagaaaggtg aaacactgct gagtcctttg 5580 gtgatgtgtg gtccccatgg cctcaagttc ctgaagcctg tggagctgcg cttaccacac 5640 tgtgcgtcca tgactcctga cggttggtct tttgctctaa aatcatccga ctcctcgtcg 5700 ggtgatccta aaacctggca aaacaagtgt cttcccggag atccaaatta tctcgttgga 5760 gcaaactgtg tttctgtcct tattgaccac ttttaactct tgaaatatag gaacttaaat 5820 aatgtgaaac tggattaaac ttaatctaaa tggaaccact ctatcaagta ttataccttt 5880 tttagagttg atactacagt ttgttagtat gaggcatttg tttgaactga taaagatgag 5940 tgagcatgcc cctgaaccat ggtcggaaaa catgctacac actgcatgtt tgtgattgac 6000 gggactgttg gtattggcta gaggttcaaa gatattttgc tttgtgattt ttgtaatttt 6060 tttatcgtca ctgcttaact tcacatattg atttccgtta aaataccagc cagtaaatgg 6120 gggtgcattt gaggtctgtt ctttccaaag tacactgttt caaactttac tatggccctg 6180 gcctagcata cgtacacatt ttattttatt atgcatgaag taatatgcac acatttttta 6240 aatgcacctg gaatatataa ccagtgttgt ggatttaaca gaaatgtaca gcaaggagat 6300 ttacaactgg gggagggtga agtgaagaca atgacttact gtacatgaaa acacattttt 6360 cttagggaag gatacaaaag catgtgagac tggttccatg gcctcttcag atctctaact 6420 tcaccatatt accacagaca tactaaccag cagaaatgcc ttaccctcat gttcttaatt 6480 cttagctcat tctccttgtg ttactaagtt tttatggctt ttgtgcatta tctagatact 6540 gtatcatgac aaagactgag tacgttgtgc atttggtggt ttcagaaatg tgttatcacc 6600 cagaagaaaa tagtggtgtg atttggggat atttttttct tttcttttct tttctttttt 6660 tttttttttg acaaggggca gtggtggttt tctgttcttt ctggctatgc atttgaaaat 6720 tttgatgttt taaggatgct tgtacataat gcgtgcatac cacttttgtt cttggtttgt 6780 aaattaactt ttataaactt tacctttttt atacataaac aagaccacgt ttctaaaggc 6840 tacctttgta ttctctcctg tacctcttga gccttgaact ttgacctctg cagcaataaa 6900 gcagcgtttc tatgacacat gcaaggtcat tttttttaag aaaaaggatg cacagagttg 6960 ttacattttt aagtgctgca tttaaaagat acagttactc agaattctct agtttgatta 7020 aattcttgca aagtatccct actgtaattt gtgatacaat gctgtgccct aaagtgtatt 7080 tttttactaa tagacaattt attatggcac atcagcacga tttctgttta gataatacac 7140 cactacattc tgttaatcat taggtgtgac tgaatttctt ttgccgttat taaaaatctc 7200 aaatttctaa atctccaaaa taaaactttt taaaataaag tgctggcttg gtctgtttgc 7260 ccactgtttt ctagtttcat gcagctttat aatcctgttt taaaatcctg cacacaaatc 7320 cctatcaccc agcgtcacct accacctcgt cgtctggtgt tgcatgcaga atttctcccc 7380 ttggccagca tgtacagatg ggtgggcagt gctcatctga agggctcaga ctgaagtggg 7440 gcagaaggac ctggagacag agtgggagaa ggcagcaggc cgacttcccc ctgtgggtaa 7500 acacacaccc ctgcgtggag aaacacccct gcatggggac acacgtgcgt ttgtgtgtgt 7560 gcgtgtaacc atttgtatat ggttttattc cccagataaa tagcacgggc attgtttaat 7620 gtcacccaca tttgggggaa gaaaatgggt ttagtgagca taaatattcc attgtggaca 7680 tcctacttac ttaactgcca cccctgttga catttggatt attgctatag tgtttcagta 7740 aacacctttg tggactgaat ccatctatgt ggattttatt tttttcatct ttgttaaggt 7800 ataatttaca tagagtaagt tactgttttt aaaatgtata gttcaaattt tgacaaacac 7860 atactgttta tttaccacgg ttaatacata caacagtttc tttatcttct ctaatcattt 7920 gtaccccttt atactcaacc cttcttccag cccctggcag gatgatctct tctgtttcta 7980 tagttgcctt tttgacagtg tcatataaat ggaatcatac aata 8024 <![CDATA[<210> 112]]> <![CDATA[<211> 7480]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 112]]> actccactca gcctgtgagg cgtagtaggt cgggttttct ttcatgctgt attacttatt 60 taaggaggaa aggctttgtt tccgtattac acagaatgtc actttgttcc tgaagtgtga 120 tctctggtac ttaatatgca agacaacaca ctttttaaga ggttatttca agtatggaga 180 gaaatacgtt ttcaatggat tgccacagta agagcacagc aatggaggaa acagctatat 240 gggaacaaca tacagtgacg cttcacaggg ctcctggatt tggatttgga attgcaatat 300 ctggtggacg agataatcct cattttcaga gtggggaaac gtcaatagtg atttcagatg 360 tgctgaaagg aggaccagct gaaggacagc tacaggaaaa tgaccgagtt gcaatggtta 420 acggagtttc aatggataat gttgaacatg cttttgctgt tcagcaacta aggaaaagtg 480 ggaaaaatgc aaaaattaca attagaagga agaagaaagt tcaaatacca gtaagtcgtc 540 ctgatcctga accagtatct gataatgaag aagatagtta tgatgaggaa atacatgatc 600 caagaagtgg ccggagtggt gtggttaaca gaaggagtga gaagatttgg ccgagggata 660 gaagtgcaag tagagagagg agcttgtccc cgcggtcaga caggcggtca gtggcttcca 720 gccagcctgc taaacctact aaagtcacac tggtgaaatc ccggaaaaat gaagaatatg 780 gtcttcgatt ggcaagccat atatttgtta aggaaatttc acaagatagt ttggcagcaa 840 gagatggcaa tattcaagaa ggtgatgttg tattgaagat aaatggtact gtgacagaaa 900 atatgtcatt gacagatgca aagacattga tagaaaggtc taaaggcaaa ttaaaaatgg 960 tagttcaaag agatgaacgg gctacgctat tgaatgtccc tgatctttct gacagcatcc 1020 actctgctaa tgcctctgag agagacgaca tttcagaaat tcagtcactg gcatcagatc 1080 attctggtcg atcacacgat aggcctcccc gccgcagccg gtcacgatct cctgaccagc 1140 ggtcagagcc ttctgatcat tccaggcact cgccgcagca gccaagcaat ggcagtctcc 1200 ggagtagaga tgaagagaga atttctaaac ctggggctgt ctcaactcct gtaaagcatg 1260 ctgatgatca cacacctaaa acagtggaag aagttacagt tgaaagaaat gagaaacaaa 1320 caccttctct tccagaacca aagcctgtgt atgcccaagt tgggcaacca gatgtggatt 1380 tacctgtcag tccatctgat ggtgtcctac ctaattcaac tcatgaagat gggattcttc 1440 ggcccagcat gaaattggta aaattcagaa aaggagatag tgtgggtttg cggctggctg 1500 gtggaaatga tgttggaata tttgtagctg gcgttctaga agatagccct gcagccaagg 1560 aaggcttaga ggaaggtgat caaattctca gggtaaacaa cgtagatttt acaaatatca 1620 taagagaaga agccgtcctt ttcctgcttg acctccctaa aggagaagaa gtgaccatat 1680 tggctcagaa gaagaaggat gtttatcgtc gcattgtaga atcagatgta ggagattctt 1740 tctatattag aacccatttt gaatatgaaa aggaatctcc ctatggactt agttttaaca 1800 aaggagaggt gttccgtgtt gtggatacct tgtacaatgg aaaactgggc tcttggcttg 1860 ctattcgaat tggtaaaaat cataaggagg tagaacgagg catcatccct aataagaaca 1920 gagctgagca gctagccagt gtacagtata cacttccaaa aacagcaggc ggagaccgtg 1980 ctgacttctg gagattcaga ggtcttcgca gctccaagag aaatcttcga aaaagcagag 2040 aggatttgtc cgctcagcct gttcaaacaa agtttccagc ttatgaaaga gtggttcttc 2100 gagaagctgg atttctgagg cctgtaacca tttttggacc aatagctgat gttgccagag 2160 aaaagctggc aagagaagaa ccagatattt atcaaattgc aaagagtgaa ccacgagacg 2220 ctggaactga ccaacgtagc tctggcatta ttcgcctgca tacaataaag caaatcatag 2280 atcaagacaa acatgcttta ttagatgtaa caccaaatgc agttgatcgt cttaactatg 2340 cccagtggta tccaattgtt gtatttctta accctgattc taagcaagga gtaaaaacaa 2400 tgagaatgag gttatgtcca gaatctcgga aaagtgccag gaagttatac gagcgatctc 2460 ataaacttcg taaaaataat caccatcttt ttacaactac aattaactta aattcaatga 2520 atgatggttg gtatggtgcg ctgaaagaag caattcaaca acagcaaaac cagctggtat 2580 gggtttccga gggaaaggcg gatggtgcta caagtgatga ccttgatttg catgatgatc 2640 gtctgtccta cctgtcagct ccaggtagtg aatactcaat gtatagcacg gacagtagac 2700 acacttctga ctatgaagac acagacacag aaggcggggc ctacactgat caagaactag 2760 atgaaactct taatgatgag gttgggactc caccggagtc tgccattaca cggtcctctg 2820 agcctgtaag agaggactcc tctggaatgc atcatgaaaa ccaaacatat cctccttact 2880 caccacaagc gcagccacaa ccaattcata gaatagactc ccctggattt aagccagcct 2940 ctcaacaggt gtatagaaag gatccatatc ccgaggaaat gatgaggcag aaccatgttt 3000 tgaaacagcc agccgttagt cacccagggc acaggccaga caaagagcct aatctgacct 3060 atgaacccca actcccatac gtagagaaac aagccagcag agacctcgag cagcccacat 3120 acagatacga gtcctcaagc tatacggacc agttttctcg aaactatgaa catcgtctgc 3180 gatacgaaga tcgcgtcccc atgtatgaag aacagtggtc atattatgat gacaaacagc 3240 cctacccatc tcggccacct tttgataatc agcactctca agaccttgac tccagacagc 3300 atcccgaaga gtcctcagaa cgagggtact ttccacgttt tgaagagcca gcccctctgt 3360 cttacgacag cagaccacgt tacgaacagg cacctagagc atccgccctg cggcacgaag 3420 agcagccagc tcctgggtat gacacacatg gtagactcag accggaagcc cagccccacc 3480 cttcagcagg gcccaagcct gcagagtcca agcagtattt tgagcaatat tcacgcagtt 3540 acgagcaagt accaccccaa ggatttacct ctagagcagg tcattttgag cctctccatg 3600 gtgctgcagc tgtccctccg ctgatacctt catctcagca taagccagaa gctctgcctt 3660 caaacaccaa accactgcct ccacccccaa ctcaaaccga agaagaggaa gatccagcaa 3720 tgaagccaca gtctgtactc accagagtta agatgtttga aaacaaaaga tctgcatcct 3780 tagagaccaa gaaggatgta aatgacactg gcagttttaa gcctccagaa gtagcatcta 3840 aaccttcagg tgctcccatc attggtccca aacccacttc tcagaatcaa ttcagtgaac 3900 atgacaaaac tctgtacagg atcccagaac ctcaaaaacc tcaactgaag ccacctgaag 3960 atattgttcg gtccaatcat tatgaccctg aagaagatga agaatattat cgaaaacagc 4020 tgtcatactt tgaccgaaga agttttgaga ataagcctcc tgcacacatt gccgccagcc 4080 atctctccga gcctgcaaag ccagcgcatt ctcagaatca atcaaatttt tctagttatt 4140 cttcaaaggg aaagcctcct gaagctgatg gtgtggatag atcatttggc gagaaacgct 4200 atgaacccat ccaggccact ccccctcctc ctccattgcc ctcgcagtat gcccagccat 4260 ctcagcctgt caccagcgcg tctctccaca tacattctaa gggagcacat ggtgaaggta 4320 attcagtgtc attggatttt cagaattcct tagtgtccaa accagaccca cctccatctc 4380 agaataagcc agcaactttc agaccaccaa accgagaaga tactgctcag gcagctttct 4440 atccccagaa aagttttcca gataaagccc cagttaatgg aactgaacag actcagaaaa 4500 cagtcactcc agcatacaat cgattcacac caaaaccata tacaagttct gcccgaccat 4560 ttgaacgcaa gtttgaaagt cctaaattca atcacaatct tctgccaagt gaaactgcac 4620 ataaacctga cttgtcttca aaaactccca cttctccaaa aactcttgtg aaatcgcaca 4680 gtttggcaca gcctcctgag tttgacagtg gagttgaaac tttctctatc catgcagaga 4740 agcctaaata tcaaataaat aatatcagca cagtgcctaa agctattcct gtgagtcctt 4800 cagctgtgga agaggatgaa gatgaagatg gtcatactgt ggtggccaca gcccgaggca 4860 tatttaacag caatgggggc gtgctgagtt ccatagaaac tggtgttagt ataattatcc 4920 ctcaaggagc cattcccgaa ggagttgagc aggaaatcta tttcaaggtc tgccgggaca 4980 acagcatcct tccaccttta gataaagaga aaggtgaaac actgctgagt cctttggtga 5040 tgtgtggtcc ccatggcctc aagttcctga agcctgtgga gctgcgctta ccacactgtg 5100 cgtccatgac tcctgacggt tggtcttttg ctctaaaatc atccgactcc tcgtcgggtg 5160 atcctaaaac ctggcaaaac aagtgtcttc ccggagatcc aaattatctc gttggagcaa 5220 actgtgtttc tgtccttatt gaccactttt aactcttgaa atataggaac ttaaataatg 5280 tgaaactgga ttaaacttaa tctaaatgga accactctat caagtattat acctttttta 5340 gagttgatac tacagtttgt tagtatgagg catttgtttg aactgataaa gatgagtgag 5400 catgcccctg aaccatggtc ggaaaacatg ctacacactg catgtttgtg attgacggga 5460 ctgttggtat tggctagagg ttcaaagata ttttgctttg tgatttttgt aattttttta 5520 tcgtcactgc ttaacttcac atattgattt ccgttaaaat accagccagt aaatgggggt 5580 gcatttgagg tctgttcttt ccaaagtaca ctgtttcaaa ctttactatg gccctggcct 5640 agcatacgta cacattttat tttattatgc atgaagtaat atgcacacat tttttaaatg 5700 cacctggaat atataaccag tgttgtggat ttaacagaaa tgtacagcaa ggagatttac 5760 aactggggga gggtgaagtg aagacaatga cttactgtac atgaaaacac atttttctta 5820 gggaaggata caaaagcatg tgagactggt tccatggcct cttcagatct ctaacttcac 5880 catattacca cagacatact aaccagcaga aatgccttac cctcatgttc ttaattctta 5940 gctcattctc cttgtgttac taagttttta tggcttttgt gcattatcta gatactgtat 6000 catgacaaag actgagtacg ttgtgcattt ggtggtttca gaaatgtgtt atcacccaga 6060 agaaaatagt ggtgtgattt ggggatattt ttttcttttc ttttcttttc tttttttttt 6120 tttttgacaa ggggcagtgg tggttttctg ttctttctgg ctatgcattt gaaaattttg 6180 atgttttaag gatgcttgta cataatgcgt gcataccact tttgttcttg gtttgtaaat 6240 taacttttat aaactttacc ttttttatac ataaacaaga ccacgtttct aaaggctacc 6300 tttgtattct ctcctgtacc tcttgagcct tgaactttga cctctgcagc aataaagcag 6360 cgtttctatg acacatgcaa ggtcattttt tttaagaaaa aggatgcaca gagttgttac 6420 atttttaagt gctgcattta aaagatacag ttactcagaa ttctctagtt tgattaaatt 6480 cttgcaaagt atccctactg taatttgtga tacaatgctg tgccctaaag tgtatttttt 6540 tactaataga caatttatta tggcacatca gcacgatttc tgtttagata atacaccact 6600 acattctgtt aatcattagg tgtgactgaa tttcttttgc cgttattaaa aatctcaaat 6660 ttctaaatct ccaaaataaa actttttaaa ataaagtgct ggcttggtct gtttgcccac 6720 tgttttctag tttcatgcag ctttataatc ctgttttaaa atcctgcaca caaatcccta 6780 tcacccagcg tcacctacca cctcgtcgtc tggtgttgca tgcagaattt ctccccttgg 6840 ccagcatgta cagatgggtg ggcagtgctc atctgaaggg ctcagactga agtggggcag 6900 aaggacctgg agacagagtg ggagaaggca gcaggccgac ttccccctgt gggtaaacac 6960 acacccctgc gtggagaaac acccctgcat ggggacacac gtgcgtttgt gtgtgtgcgt 7020 gtaaccattt gtatatggtt ttattcccca gataaatagc acgggcattg tttaatgtca 7080 cccacatttg ggggaagaaa atgggtttag tgagcataaa tattccattg tggacatcct 7140 acttacttaa ctgccacccc tgttgacatt tggattattg ctatagtgtt tcagtaaaca 7200 cctttgtgga ctgaatccat ctatgtggat tttatttttt tcatctttgt taaggtataa 7260 tttacataga gtaagttact gtttttaaaa tgtatagttc aaattttgac aaacacatac 7320 tgtttattta ccacggttaa tacatacaac agtttcttta tcttctctaa tcatttgtac 7380 ccctttatac tcaacccttc ttccagcccc tggcaggatg atctcttctg tttctatagt 7440 tgcctttttg acagtgtcat ataaatggaa tcatacaata 7480 <![CDATA[<210> 113]]> <![CDATA[<211> 7190]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 113]]> gtggccgctg agttgccggc gccggctgag ccagcggacg ccgcgttcct tggcggccgc 60 cggttcccgg gaagttacgt ggcgaagccg gcttccgagg agacgccggg aggccacggg 120 tgctgctgac gggcgggcga ccgggcgagg ccgacgtggc cgggctgcga aagctgcggg 180 aggccgagtg ggtggccgcg ctcggaggga ggtgccggtc gggcgcgccc cgtggagaag 240 acccgggcgg ggcgggcgct tcccggactt ttgtccgagt tgaattccct ccccctgggc 300 cgggcccttc cggccgcccc cgcccgtgcc ccgctcgctc tcgggagatg tttatttggg 360 ctgtggcgtg aggagcgggc gggccagcgc cgcggagttt cgggtccgag gagcctcgcg 420 cggcgctgga gagagacaag atgtccgcca gagctgcggc cgccaagagc acagcaatgg 480 aggaaacagc tatatgggaa caacatacag tgacgcttca cagggctcct ggatttggat 540 ttggaattgc aatatctggt ggacgagata atcctcattt tcagagtggg gaaacgtcaa 600 tagtgatttc agatgtgctg aaaggaggac cagctgaagg acagctacag gaaaatgacc 660 gagttgcaat ggttaacgga gtttcaatgg ataatgttga acatgctttt gctgttcagc 720 aactaaggaa aagtgggaaa aatgcaaaaa ttacaattag aaggaagaag aaagttcaaa 780 taccagtaag tcgtcctgat cctgaaccag tatctgataa tgaagaagat agttatgatg 840 aggaaataca tgatccaaga agtggccgga gtggtgtggt taacagaagg agtgagaaga 900 tttggccgag ggatagaagt gcaagtagag agaggagctt gtccccgcgg tcagacaggc 960 ggtcagtggc ttccagccag cctgctaaac ctactaaagt cacactggtg aaatcccgga 1020 aaaatgaaga atatggtctt cgattggcaa gccatatatt tgttaaggaa atttcacaag 1080 atagtttggc agcaagagat ggcaatattc aagaaggtga tgttgtattg aagataaatg 1140 gtactgtgac agaaaatatg tcattgacag atgcaaagac attgatagaa aggtctaaag 1200 gcaaattaaa aatggtagtt caaagagatg aacgggctac gctattgaat gtccctgatc 1260 tttctgacag catccactct gctaatgcct ctgagagaga cgacatttca gaaattcagt 1320 cactggcatc agatcattct ggtcgatcac acgataggcc tccccgccgc agccggtcac 1380 gatctcctga ccagcggtca gagccttctg atcattccag gcactcgccg cagcagccaa 1440 gcaatggcag tctccggagt agagatgaag agagaatttc taaacctggg gctgtctcaa 1500 ctcctgtaaa gcatgctgat gatcacacac ctaaaacagt ggaagaagtt acagttgaaa 1560 gaaatgagaa acaaacacct tctcttccag aaccaaagcc tgtgtatgcc caagttgggc 1620 aaccagatgt ggatttacct gtcagtccat ctgatggtgt cctacctaat tcaactcatg 1680 aagatgggat tcttcggccc agcatgaaat tggtaaaatt cagaaaagga gatagtgtgg 1740 gtttgcggct ggctggtgga aatgatgttg gaatatttgt agctggcgtt ctagaagata 1800 gccctgcagc caaggaaggc ttagaggaag gtgatcaaat tctcagggta aacaacgtag 1860 attttacaaa tatcataaga gaagaagccg tccttttcct gcttgacctc cctaaaggag 1920 aagaagtgac catattggct cagaagaaga aggatgttta tcgtcgcatt gtagaatcag 1980 atgtaggaga ttctttctat attagaaccc attttgaata tgaaaaggaa tctccctatg 2040 gacttagttt taacaaagga gaggtgttcc gtgttgtgga taccttgtac aatggaaaac 2100 tgggctcttg gcttgctatt cgaattggta aaaatcataa ggaggtagaa cgaggcatca 2160 tccctaataa gaacagagct gagcagctag ccagtgtaca gtatacactt ccaaaaacag 2220 caggcggaga ccgtgctgac ttctggagat tcagaggtct tcgcagctcc aagagaaatc 2280 ttcgaaaaag cagagaggat ttgtccgctc agcctgttca aacaaagttt ccagcttatg 2340 aaagagtggt tcttcgagaa gctggatttc tgaggcctgt aaccattttt ggaccaatag 2400 ctgatgttgc cagagaaaag ctggcaagag aagaaccaga tatttatcaa attgcaaaga 2460 gtgaaccacg agacgctgga actgaccaac gtagctctgg cattattcgc ctgcatacaa 2520 taaagcaaat catagatcaa gacaaacatg ctttattaga tgtaacacca aatgcagttg 2580 atcgtcttaa ctatgcccag tggtatccaa ttgttgtatt tcttaaccct gattctaagc 2640 aaggagtaaa aacaatgaga atgaggttat gtccagaatc tcggaaaagt gccaggaagt 2700 tatacgagcg atctcataaa cttcgtaaaa ataatcacca tctttttaca actacaatta 2760 acttaaattc aatgaatgat ggttggtatg gtgcgctgaa agaagcaatt caacaacagc 2820 aaaaccagct ggtatgggtt tccgagggaa aggcggatgg tgctacaagt gatgaccttg 2880 atttgcatga tgatcgtctg tcctacctgt cagctccagg tagtgaatac tcaatgtata 2940 gcacggacag tagacacact tctgactatg aagacacaga cacagaaggc ggggcctaca 3000 ctgatcaaga actagatgaa actcttaatg atgaggttgg gactccaccg gagtctgcca 3060 ttacacggtc ctctgagcct gtaagagagg actcctctgg aatgcatcat gaaaaccaaa 3120 catatcctcc ttactcacca caagcgcagc cacaaccaat tcatagaata gactcccctg 3180 gatttaagcc agcctctcaa cagaaagcag aagcttcatc tccagtccct tacctttcgc 3240 ctgaaacaaa cccagcatca tcaacctctg ctgttaatca taatgtaaat ttaactaatg 3300 tcagactgga ggagcccacc ccagctcctt ccacctctta ctcaccacaa gctgattctt 3360 taagaacacc aagtactgag gcagctcaca taatgctaag agatcaagaa ccatcattgt 3420 cgtcgcatgt agatccaaca aaggtgtata gaaaggatcc atatcccgag gaaatgatga 3480 ggcagaacca tgttttgaaa cagccagccg ttagtcaccc agggcacagg ccagacaaag 3540 agcctaatct gacctatgaa ccccaactcc catacgtaga gaaacaagcc agcagagacc 3600 tcgagcagcc cacatacaga tacgagtcct caagctatac ggaccagttt tctcgaaact 3660 atgaacatcg tctgcgatac gaagatcgcg tccccatgta tgaagaacag tggtcatatt 3720 atgatgacaa acagccctac ccatctcggc caccttttga taatcagcac tctcaagacc 3780 ttgactccag acagcatccc gaagagtcct cagaacgagg gtactttcca cgttttgaag 3840 agccagcccc tctgtcttac gacagcagac cacgttacga acaggcacct agagcatccg 3900 ccctgcggca cgaagagcag ccagctcctg ggtatgacac acatggtaga ctcagaccgg 3960 aagcccagcc ccacccttca gcagggccca agcctgcaga gtccaagcag tattttgagc 4020 aatattcacg cagttacgag caagtaccac cccaaggatt tacctctaga gcaggtcatt 4080 ttgagcctct ccatggtgct gcagctgtcc ctccgctgat accttcatct cagcataagc 4140 cagaagctct gccttcaaac accaaaccac tgcctccacc cccaactcaa accgaagaag 4200 aggaagatcc agcaatgaag ccacagtctg tactcaccag agttaagatg tttgaaaaca 4260 aaagatctgc atccttagag accaagaagg atgtaaatga cactggcagt tttaagcctc 4320 cagaagtagc atctaaacct tcaggtgctc ccatcattgg tcccaaaccc acttctcaga 4380 atcaattcag tgaacatgac aaaactctgt acaggatccc agaacctcaa aaacctcaac 4440 tgaagccacc tgaagatatt gttcggtcca atcattatga ccctgaagaa gatgaagaat 4500 attatcgaaa acagctgtca tactttgacc gaagaagttt tgagaataag cctcctgcac 4560 acattgccgc cagccatctc tccgagcctg caaagccagc gcattctcag aatcaatcaa 4620 atttttctag ttattcttca aagggaaagc ctcctgaagc tgatggtgtg gatagatcat 4680 ttggcgagaa acgctatgaa cccatccagg ccactccccc tcctcctcca ttgccctcgc 4740 agtatgccca gccatctcag cctgtcacca gcgcgtctct ccacatacat tctaagggag 4800 cacatggtga aggtaattca gtgtcattgg attttcagaa ttccttagtg tccaaaccag 4860 acccacctcc atctcagaat aagccagcaa ctttcagacc accaaaccga gaagatactg 4920 ctcaggcagc tttctatccc cagaaaagtt ttccagataa agccccagtt aatggaactg 4980 aacagactca gaaaacagtc actccagcat acaatcgatt cacaccaaaa ccatatacaa 5040 gttctgcccg accatttgaa cgcaagtttg aaagtcctaa attcaatcac aatcttctgc 5100 caagtgaaac tgcacataaa cctgacttgt cttcaaaaac tcccacttct ccaaaaactc 5160 ttgtgaaatc gcacagtttg gcacagcctc ctgagtttga cagtggagtt gaaactttct 5220 ctatccatgc agagaagcct aaatatcaaa taaataatat cagcacagtg cctaaagcta 5280 ttcctgtgag tccttcagct gtggaagagg atgaagatga agatggtcat actgtggtgg 5340 ccacagcccg aggcatattt aacagcaatg ggggcgtgct gagttccata gaaactggtg 5400 ttagtataat tatccctcaa ggagccattc ccgaaggagt tgagcaggaa atctatttca 5460 aggtctgccg ggacaacagc atccttccac ctttagataa agagaaaggt gaaacactgc 5520 tgagtccttt ggtgatgtgt ggtccccatg gcctcaagtt cctgaagcct gtggagctgc 5580 gcttaccaca ctgtgcgtcc atgactcctg acggttggtc ttttgctcta aaatcatccg 5640 actcctcgtc gggtgatcct aaaacctggc aaaacaagtg tcttcccgga gatccaaatt 5700 atctcgttgg agcaaactgt gtttctgtcc ttattgacca cttttaactc ttgaaatata 5760 ggaacttaaa taatgtgaaa ctggattaaa cttaatctaa atggaaccac tctatcaagt 5820 attatacctt ttttagagtt gatactacag tttgttagta tgaggcattt gtttgaactg 5880 ataaagatga gtgagcatgc ccctgaacca tggtcggaaa acatgctaca cactgcatgt 5940 ttgtgattga cgggactgtt ggtattggct agaggttcaa agatattttg ctttgtgatt 6000 tttgtaattt ttttatcgtc actgcttaac ttcacatatt gatttccgtt aaaataccag 6060 ccagtaaatg ggggtgcatt tgaggtctgt tctttccaaa gtacactgtt tcaaacttta 6120 ctatggccct ggcctagcat acgtacacat tttattttat tatgcatgaa gtaatatgca 6180 cacatttttt aaatgcacct ggaatatata accagtgttg tggatttaac agaaatgtac 6240 agcaaggaga tttacaactg ggggagggtg aagtgaagac aatgacttac tgtacatgaa 6300 aacacatttt tcttagggaa ggatacaaaa gcatgtgaga ctggttccat ggcctcttca 6360 gatctctaac ttcaccatat taccacagac atactaacca gcagaaatgc cttaccctca 6420 tgttcttaat tcttagctca ttctccttgt gttactaagt ttttatggct tttgtgcatt 6480 atctagatac tgtatcatga caaagactga gtacgttgtg catttggtgg tttcagaaat 6540 gtgttatcac ccagaagaaa atagtggtgt gatttgggga tatttttttc ttttcttttc 6600 ttttcttttt tttttttttt gacaaggggc agtggtggtt ttctgttctt tctggctatg 6660 catttgaaaa ttttgatgtt ttaaggatgc ttgtacataa tgcgtgcata ccacttttgt 6720 tcttggtttg taaattaact tttataaact ttaccttttt tatacataaa caagaccacg 6780 tttctaaagg ctacctttgt attctctcct gtacctcttg agccttgaac tttgacctct 6840 gcagcaataa agcagcgttt ctatgacaca tgcaaggtca ttttttttaa gaaaaaggat 6900 gcacagagtt gttacatttt taagtgctgc atttaaaaga tacagttact cagaattctc 6960 tagtttgatt aaattcttgc aaagtatccc tactgtaatt tgtgatacaa tgctgtgccc 7020 taaagtgtat ttttttacta atagacaatt tattatggca catcagcacg atttctgttt 7080 agataataca ccactacatt ctgttaatca ttaggtgtga ctgaatttct tttgccgtta 7140 ttaaaaatct caaatttcta aatctccaaa ataaaacttt ttaaaataaa 7190 <![CDATA[<210> 114]]> <![CDATA[<211> 7964]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 114]]> gccgccgggc cacggcctgc aggggtggaa ggggcggcgg cggcgggagc tgcgggccac 60 gcacggcggc ggcggcggga gcggccgggc acgcacggcg acggcggcgg cgggagcggg 120 agcccgggcc acgcacggcc gcagctgcgg gtgcggcggg cgcgggagcg gtgggagctg 180 tggtggcggc ggatggccca gagctgatct atgcggcgcc tggaggggct gtgtctgcgg 240 cggcggcgga ggcggcgggg ccctgcccgc gagcggagcg gggacaagat gaagtaccag 300 aaatacctga cggtgctgca gatggccatc ggcgtcaccc cctccaaccg cggcagcctc 360 ctgccgctca agaggaagct gtgggtaacg ccatcctctg aaaatcctaa tggtgctact 420 tctagtgtca gccaaggaaa accctcttta agacgaatta aagggagatt acacagaagc 480 aaaagccttg atagcatgga tttctgtgag ctcactagca cagcaatgga ggaaacagct 540 atatgggaac aacatacagt gacgcttcac agggctcctg gatttggatt tggaattgca 600 atatctggtg gacgagataa tcctcatttt cagagtgggg aaacgtcaat agtgatttca 660 gatgtgctga aaggaggacc agctgaagga cagctacagg aaaatgaccg agttgcaatg 720 gttaacggag tttcaatgga taatgttgaa catgcttttg ctgttcagca actaaggaaa 780 agtgggaaaa atgcaaaaat tacaattaga aggaagaaga aagttcaaat accagtaagt 840 cgtcctgatc ctgaaccagt atctgataat gaagaagata gttatgatga ggaaatacat 900 gatccaagaa gtggccggag tggtgtggtt aacagaagga gtgagaagat ttggccgagg 960 gatagaagtg caagtagaga gaggagcttg tccccgcggt cagacaggcg gtcagtggct 1020 tccagccagc ctgctaaacc tactaaagtc acactggtga aatcccggaa aaatgaagaa 1080 tatggtcttc gattggcaag ccatatattt gttaaggaaa tttcacaaga tagtttggca 1140 gcaagagatg gcaatattca agaaggtgat gttgtattga agataaatgg tactgtgaca 1200 gaaaatatgt cattgacaga tgcaaagaca ttgatagaaa ggtctaaagg caaattaaaa 1260 atggtagttc aaagagatga acgggctacg ctattgaatg tccctgatct ttctgacagc 1320 atccactctg ctaatgcctc tgagagagac gacatttcag aaattcagtc actggcatca 1380 gatcattctg gtcgatcaca cgataggcct ccccgccgca gccggtcacg atctcctgac 1440 cagcggtcag agccttctga tcattccagg cactcgccgc agcagccaag caatggcagt 1500 ctccggagta gagatgaaga gagaatttct aaacctgggg ctgtctcaac tcctgtaaag 1560 catgctgatg atcacacacc taaaacagtg gaagaagtta cagttgaaag aaatgagaaa 1620 caaacacctt ctcttccaga accaaagcct gtgtatgccc aagttgggca accagatgtg 1680 gatttacctg tcagtccatc tgatggtgtc ctacctaatt caactcatga agatgggatt 1740 cttcggccca gcatgaaatt ggtaaaattc agaaaaggag atagtgtggg tttgcggctg 1800 gctggtggaa atgatgttgg aatatttgta gctggcgttc tagaagatag ccctgcagcc 1860 aaggaaggct tagaggaagg tgatcaaatt ctcagggtaa acaacgtaga ttttacaaat 1920 atcataagag aagaagccgt ccttttcctg cttgacctcc ctaaaggaga agaagtgacc 1980 atattggctc agaagaagaa ggatgtttat cgtcgcattg tagaatcaga tgtaggagat 2040 tctttctata ttagaaccca ttttgaatat gaaaaggaat ctccctatgg acttagtttt 2100 aacaaaggag aggtgttccg tgttgtggat accttgtaca atggaaaact gggctcttgg 2160 cttgctattc gaattggtaa aaatcataag gaggtagaac gaggcatcat ccctaataag 2220 aacagagctg agcagctagc cagtgtacag tatacacttc caaaaacagc aggcggagac 2280 cgtgctgact tctggagatt cagaggtctt cgcagctcca agagaaatct tcgaaaaagc 2340 agagaggatt tgtccgctca gcctgttcaa acaaagtttc cagcttatga aagagtggtt 2400 cttcgagaag ctggatttct gaggcctgta accatttttg gaccaatagc tgatgttgcc 2460 agagaaaagc tggcaagaga agaaccagat atttatcaaa ttgcaaagag tgaaccacga 2520 gacgctggaa ctgaccaacg tagctctggc attattcgcc tgcatacaat aaagcaaatc 2580 atagatcaag acaaacatgc tttattagat gtaacaccaa atgcagttga tcgtcttaac 2640 tatgcccagt ggtatccaat tgttgtattt cttaaccctg attctaagca aggagtaaaa 2700 acaatgagaa tgaggttatg tccagaatct cggaaaagtg ccaggaagtt atacgagcga 2760 tctcataaac ttcgtaaaaa taatcaccat ctttttacaa ctacaattaa cttaaattca 2820 atgaatgatg gttggtatgg tgcgctgaaa gaagcaattc aacaacagca aaaccagctg 2880 gtatgggttt ccgagggaaa ggcggatggt gctacaagtg atgaccttga tttgcatgat 2940 gatcgtctgt cctacctgtc agctccaggt agtgaatact caatgtatag cacggacagt 3000 agacacactt ctgactatga agacacagac acagaaggcg gggcctacac tgatcaagaa 3060 ctagatgaaa ctcttaatga tgaggttggg actccaccgg agtctgccat tacacggtcc 3120 tctgagcctg taagagagga ctcctctgga atgcatcatg aaaaccaaac atatcctcct 3180 tactcaccac aagcgcagcc acaaccaatt catagaatag actcccctgg atttaagcca 3240 gcctctcaac agaaagcaga agcttcatct ccagtccctt acctttcgcc tgaaacaaac 3300 ccagcatcat caacctctgc tgttaatcat aatgtaaatt taactaatgt cagactggag 3360 gagcccaccc cagctccttc cacctcttac tcaccacaag ctgattcttt aagaacacca 3420 agtactgagg cagctcacat aatgctaaga gatcaagaac catcattgtc gtcgcatgta 3480 gatccaacaa aggtgtatag aaaggatcca tatcccgagg aaatgatgag gcagaaccat 3540 gttttgaaac agccagccgt tagtcaccca gggcacaggc cagacaaaga gcctaatctg 3600 acctatgaac cccaactccc atacgtagag aaacaagcca gcagagacct cgagcagccc 3660 acatacagat acgagtcctc aagctatacg gaccagtttt ctcgaaacta tgaacatcgt 3720 ctgcgatacg aagatcgcgt ccccatgtat gaagaacagt ggtcatatta tgatgacaaa 3780 cagccctacc catctcggcc accttttgat aatcagcact ctcaagacct tgactccaga 3840 cagcatcccg aagagtcctc agaacgaggg tactttccac gttttgaaga gccagcccct 3900 ctgtcttacg acagcagacc acgttacgaa caggcaccta gagcatccgc cctgcggcac 3960 gaagagcagc cagctcctgg gtatgacaca catggtagac tcagaccgga agcccagccc 4020 cacccttcag cagggcccaa gcctgcagag tccaagcagt attttgagca atattcacgc 4080 agttacgagc aagtaccacc ccaaggattt acctctagag caggtcattt tgagcctctc 4140 catggtgctg cagctgtccc tccgctgata ccttcatctc agcataagcc agaagctctg 4200 ccttcaaaca ccaaaccact gcctccaccc ccaactcaaa ccgaagaaga ggaagatcca 4260 gcaatgaagc cacagtctgt actcaccaga gttaagatgt ttgaaaacaa aagatctgca 4320 tccttagaga ccaagaagga tgtaaatgac actggcagtt ttaagcctcc agaagtagca 4380 tctaaacctt caggtgctcc catcattggt cccaaaccca cttctcagaa tcaattcagt 4440 gaacatgaca aaactctgta caggatccca gaacctcaaa aacctcaact gaagccacct 4500 gaagatattg ttcggtccaa tcattatgac cctgaagaag atgaagaata ttatcgaaaa 4560 cagctgtcat actttgaccg aagaagtttt gagaataagc ctcctgcaca cattgccgcc 4620 agccatctct ccgagcctgc aaagccagcg cattctcaga atcaatcaaa tttttctagt 4680 tattcttcaa agggaaagcc tcctgaagct gatggtgtgg atagatcatt tggcgagaaa 4740 cgctatgaac ccatccaggc cactccccct cctcctccat tgccctcgca gtatgcccag 4800 ccatctcagc ctgtcaccag cgcgtctctc cacatacatt ctaagggagc acatggtgaa 4860 ggtaattcag tgtcattgga ttttcagaat tccttagtgt ccaaaccaga cccacctcca 4920 tctcagaata agccagcaac tttcagacca ccaaaccgag aagatactgc tcaggcagct 4980 ttctatcccc agaaaagttt tccagataaa gccccagtta atggaactga acagactcag 5040 aaaacagtca ctccagcata caatcgattc acaccaaaac catatacaag ttctgcccga 5100 ccatttgaac gcaagtttga aagtcctaaa ttcaatcaca atcttctgcc aagtgaaact 5160 gcacataaac ctgacttgtc ttcaaaaact cccacttctc caaaaactct tgtgaaatcg 5220 cacagtttgg cacagcctcc tgagtttgac agtggagttg aaactttctc tatccatgca 5280 gagaagccta aatatcaaat aaataatatc agcacagtgc ctaaagctat tcctgtgagt 5340 ccttcagctg tggaagagga tgaagatgaa gatggtcata ctgtggtggc cacagcccga 5400 ggcatattta acagcaatgg gggcgtgctg agttccatag aaactggtgt tagtataatt 5460 atccctcaag gagccattcc cgaaggagtt gagcaggaaa tctatttcaa ggtctgccgg 5520 gacaacagca tccttccacc tttagataaa gagaaaggtg aaacactgct gagtcctttg 5580 gtgatgtgtg gtccccatgg cctcaagttc ctgaagcctg tggagctgcg cttaccacac 5640 tgtgatccta aaacctggca aaacaagtgt cttcccggag atccaaatta tctcgttgga 5700 gcaaactgtg tttctgtcct tattgaccac ttttaactct tgaaatatag gaacttaaat 5760 aatgtgaaac tggattaaac ttaatctaaa tggaaccact ctatcaagta ttataccttt 5820 tttagagttg atactacagt ttgttagtat gaggcatttg tttgaactga taaagatgag 5880 tgagcatgcc cctgaaccat ggtcggaaaa catgctacac actgcatgtt tgtgattgac 5940 gggactgttg gtattggcta gaggttcaaa gatattttgc tttgtgattt ttgtaatttt 6000 tttatcgtca ctgcttaact tcacatattg atttccgtta aaataccagc cagtaaatgg 6060 gggtgcattt gaggtctgtt ctttccaaag tacactgttt caaactttac tatggccctg 6120 gcctagcata cgtacacatt ttattttatt atgcatgaag taatatgcac acatttttta 6180 aatgcacctg gaatatataa ccagtgttgt ggatttaaca gaaatgtaca gcaaggagat 6240 ttacaactgg gggagggtga agtgaagaca atgacttact gtacatgaaa acacattttt 6300 cttagggaag gatacaaaag catgtgagac tggttccatg gcctcttcag atctctaact 6360 tcaccatatt accacagaca tactaaccag cagaaatgcc ttaccctcat gttcttaatt 6420 cttagctcat tctccttgtg ttactaagtt tttatggctt ttgtgcatta tctagatact 6480 gtatcatgac aaagactgag tacgttgtgc atttggtggt ttcagaaatg tgttatcacc 6540 cagaagaaaa tagtggtgtg atttggggat atttttttct tttcttttct tttctttttt 6600 tttttttttg acaaggggca gtggtggttt tctgttcttt ctggctatgc atttgaaaat 6660 tttgatgttt taaggatgct tgtacataat gcgtgcatac cacttttgtt cttggtttgt 6720 aaattaactt ttataaactt tacctttttt atacataaac aagaccacgt ttctaaaggc 6780 tacctttgta ttctctcctg tacctcttga gccttgaact ttgacctctg cagcaataaa 6840 gcagcgtttc tatgacacat gcaaggtcat tttttttaag aaaaaggatg cacagagttg 6900 ttacattttt aagtgctgca tttaaaagat acagttactc agaattctct agtttgatta 6960 aattcttgca aagtatccct actgtaattt gtgatacaat gctgtgccct aaagtgtatt 7020 tttttactaa tagacaattt attatggcac atcagcacga tttctgttta gataatacac 7080 cactacattc tgttaatcat taggtgtgac tgaatttctt ttgccgttat taaaaatctc 7140 aaatttctaa atctccaaaa taaaactttt taaaataaag tgctggcttg gtctgtttgc 7200 ccactgtttt ctagtttcat gcagctttat aatcctgttt taaaatcctg cacacaaatc 7260 cctatcaccc agcgtcacct accacctcgt cgtctggtgt tgcatgcaga atttctcccc 7320 ttggccagca tgtacagatg ggtgggcagt gctcatctga agggctcaga ctgaagtggg 7380 gcagaaggac ctggagacag agtgggagaa ggcagcaggc cgacttcccc ctgtgggtaa 7440 acacacaccc ctgcgtggag aaacacccct gcatggggac acacgtgcgt ttgtgtgtgt 7500 gcgtgtaacc atttgtatat ggttttattc cccagataaa tagcacgggc attgtttaat 7560 gtcacccaca tttgggggaa gaaaatgggt ttagtgagca taaatattcc attgtggaca 7620 tcctacttac ttaactgcca cccctgttga catttggatt attgctatag tgtttcagta 7680 aacacctttg tggactgaat ccatctatgt ggattttatt tttttcatct ttgttaaggt 7740 ataatttaca tagagtaagt tactgttttt aaaatgtata gttcaaattt tgacaaacac 7800 atactgttta tttaccacgg ttaatacata caacagtttc tttatcttct ctaatcattt 7860 gtaccccttt atactcaacc cttcttccag cccctggcag gatgatctct tctgtttcta 7920 tagttgcctt tttgacagtg tcatataaat ggaatcatac aata 7964 <![CDATA[<210> 115]]> <![CDATA[<211> 7638]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 115]]> gaggaaaggc tttgtttccg tattacacag aatgtcactt tgttcctgaa gtgtgatctc 60 tggtacttaa tatgcaagac aacacacttt ttaagaggtt atttcaagta tggagagaaa 120 tacgttttca atggattgcc acagtaagag cacagcaatg gaggaaacag ctatatggga 180 acaacataca gtgacgcttc acagggctcc tggatttgga tttggaattg caatatctgg 240 tggacgagat aatcctcatt ttcagagtgg ggaaacgtca atagtgattt cagatgtgct 300 gaaaggagga ccagctgaag gacagctaca ggaaaatgac cgagttgcaa tggttaacgg 360 agtttcaatg gataatgttg aacatgcttt tgctgttcag caactaagga aaagtgggaa 420 aaatgcaaaa attacaatta gaaggaagaa gaaagttcaa ataccagtaa gtcgtcctga 480 tcctgaacca gtatctgata atgaagaaga tagttatgat gaggaaatac atgatccaag 540 aagtggccgg agtggtgtgg ttaacagaag gagtgagaag atttggccga gggatagaag 600 tgcaagtaga gagaggagct tgtccccgcg gtcagacagg cggtcagtgg cttccagcca 660 gcctgctaaa cctactaaag tcacactggt gaaatcccgg aaaaatgaag aatatggtct 720 tcgattggca agccatatat ttgttaagga aatttcacaa gatagtttgg cagcaagaga 780 tggcaatatt caagaaggtg atgttgtatt gaagataaat ggtactgtga cagaaaatat 840 gtcattgaca gatgcaaaga cattgataga aaggtctaaa ggcaaattaa aaatggtagt 900 tcaaagagat gaacgggcta cgctattgaa tgtccctgat ctttctgaca gcatccactc 960 tgctaatgcc tctgagagag acgacatttc agaaattcag tcactggcat cagatcattc 1020 tggtcgatca cacgataggc ctccccgccg cagccggtca cgatctcctg accagcggtc 1080 agagccttct gatcattcca ggcactcgcc gcagcagcca agcaatggca gtctccggag 1140 tagagatgaa gagagaattt ctaaacctgg ggctgtctca actcctgtaa agcatgctga 1200 tgatcacaca cctaaaacag tggaagaagt tacagttgaa agaaatgaga aacaaacacc 1260 ttctcttcca gaaccaaagc ctgtgtatgc ccaagttggg caaccagatg tggatttacc 1320 tgtcagtcca tctgatggtg tcctacctaa ttcaactcat gaagatggga ttcttcggcc 1380 cagcatgaaa ttggtaaaat tcagaaaagg agatagtgtg ggtttgcggc tggctggtgg 1440 aaatgatgtt ggaatatttg tagctggcgt tctagaagat agccctgcag ccaaggaagg 1500 cttagaggaa ggtgatcaaa ttctcagggt aaacaacgta gattttacaa atatcataag 1560 agaagaagcc gtccttttcc tgcttgacct ccctaaagga gaagaagtga ccatattggc 1620 tcagaagaag aaggatgttt atcgtcgcat tgtagaatca gatgtaggag attctttcta 1680 tattagaacc cattttgaat atgaaaagga atctccctat ggacttagtt ttaacaaagg 1740 agaggtgttc cgtgttgtgg ataccttgta caatggaaaa ctgggctctt ggcttgctat 1800 tcgaattggt aaaaatcata aggaggtaga acgaggcatc atccctaata agaacagagc 1860 tgagcagcta gccagtgtac agtatacact tccaaaaaca gcaggcggag accgtgctga 1920 cttctggaga ttcagaggtc ttcgcagctc caagagaaat cttcgaaaaa gcagagagga 1980 tttgtccgct cagcctgttc aaacaaagtt tccagcttat gaaagagtgg ttcttcgaga 2040 agctggattt ctgaggcctg taaccatttt tggaccaata gctgatgttg ccagagaaaa 2100 gctggcaaga gaagaaccag atatttatca aattgcaaag agtgaaccac gagacgctgg 2160 aactgaccaa cgtagctctg gcattattcg cctgcataca ataaagcaaa tcatagatca 2220 agacaaacat gctttattag atgtaacacc aaatgcagtt gatcgtctta actatgccca 2280 gtggtatcca attgttgtat ttcttaaccc tgattctaag caaggagtaa aaacaatgag 2340 aatgaggtta tgtccagaat ctcggaaaag tgccaggaag ttatacgagc gatctcataa 2400 acttcgtaaa aataatcacc atctttttac aactacaatt aacttaaatt caatgaatga 2460 tggttggtat ggtgcgctga aagaagcaat tcaacaacag caaaaccagc tggtatgggt 2520 ttccgaggga aaggcggatg gtgctacaag tgatgacctt gatttgcatg atgatcgtct 2580 gtcctacctg tcagctccag gtagtgaata ctcaatgtat agcacggaca gtagacacac 2640 ttctgactat gaagacacag acacagaagg cggggcctac actgatcaag aactagatga 2700 aactcttaat gatgaggttg ggactccacc ggagtctgcc attacacggt cctctgagcc 2760 tgtaagagag gactcctctg gaatgcatca tgaaaaccaa acatatcctc cttactcacc 2820 acaagcgcag ccacaaccaa ttcatagaat agactcccct ggatttaagc cagcctctca 2880 acagaaagca gaagcttcat ctccagtccc ttacctttcg cctgaaacaa acccagcatc 2940 atcaacctct gctgttaatc ataatgtaaa tttaactaat gtcagactgg aggagcccac 3000 cccagctcct tccacctctt actcaccaca agctgattct ttaagaacac caagtactga 3060 ggcagctcac ataatgctaa gagatcaaga accatcattg tcgtcgcatg tagatccaac 3120 aaaggtgtat agaaaggatc catatcccga ggaaatgatg aggcagaacc atgttttgaa 3180 acagccagcc gttagtcacc cagggcacag gccagacaaa gagcctaatc tgacctatga 3240 accccaactc ccatacgtag agaaacaagc cagcagagac ctcgagcagc ccacatacag 3300 atacgagtcc tcaagctata cggaccagtt ttctcgaaac tatgaacatc gtctgcgata 3360 cgaagatcgc gtccccatgt atgaagaaca gtggtcatat tatgatgaca aacagcccta 3420 cccatctcgg ccaccttttg ataatcagca ctctcaagac cttgactcca gacagcatcc 3480 cgaagagtcc tcagaacgag ggtactttcc acgttttgaa gagccagccc ctctgtctta 3540 cgacagcaga ccacgttacg aacaggcacc tagagcatcc gccctgcggc acgaagagca 3600 gccagctcct gggtatgaca cacatggtag actcagaccg gaagcccagc cccacccttc 3660 agcagggccc aagcctgcag agtccaagca gtattttgag caatattcac gcagttacga 3720 gcaagtacca ccccaaggat ttacctctag agcaggtcat tttgagcctc tccatggtgc 3780 tgcagctgtc cctccgctga taccttcatc tcagcataag ccagaagctc tgccttcaaa 3840 caccaaacca ctgcctccac ccccaactca aaccgaagaa gaggaagatc cagcaatgaa 3900 gccacagtct gtactcacca gagttaagat gtttgaaaac aaaagatctg catccttaga 3960 gaccaagaag gatgtaaatg acactggcag ttttaagcct ccagaagtag catctaaacc 4020 ttcaggtgct cccatcattg gtcccaaacc cacttctcag aatcaattca gtgaacatga 4080 caaaactctg tacaggatcc cagaacctca aaaacctcaa ctgaagccac ctgaagatat 4140 tgttcggtcc aatcattatg accctgaaga agatgaagaa tattatcgaa aacagctgtc 4200 atactttgac cgaagaagtt ttgagaataa gcctcctgca cacattgccg ccagccatct 4260 ctccgagcct gcaaagccag cgcattctca gaatcaatca aatttttcta gttattcttc 4320 aaagggaaag cctcctgaag ctgatggtgt ggatagatca tttggcgaga aacgctatga 4380 acccatccag gccactcccc ctcctcctcc attgccctcg cagtatgccc agccatctca 4440 gcctgtcacc agcgcgtctc tccacataca ttctaaggga gcacatggtg aaggtaattc 4500 agtgtcattg gattttcaga attccttagt gtccaaacca gacccacctc catctcagaa 4560 taagccagca actttcagac caccaaaccg agaagatact gctcaggcag ctttctatcc 4620 ccagaaaagt tttccagata aagccccagt taatggaact gaacagactc agaaaacagt 4680 cactccagca tacaatcgat tcacaccaaa accatataca agttctgccc gaccatttga 4740 acgcaagttt gaaagtccta aattcaatca caatcttctg ccaagtgaaa ctgcacataa 4800 acctgacttg tcttcaaaaa ctcccacttc tccaaaaact cttgtgaaat cgcacagttt 4860 ggcacagcct cctgagtttg acagtggagt tgaaactttc tctatccatg cagagaagcc 4920 taaatatcaa ataaataata tcagcacagt gcctaaagct attcctgtga gtccttcagc 4980 tgtggaagag gatgaagatg aagatggtca tactgtggtg gccacagccc gaggcatatt 5040 taacagcaat gggggcgtgc tgagttccat agaaactggt gttagtataa ttatccctca 5100 aggagccatt cccgaaggag ttgagcagga aatctatttc aaggtctgcc gggacaacag 5160 catccttcca cctttagata aagagaaagg tgaaacactg ctgagtcctt tggtgatgtg 5220 tggtccccat ggcctcaagt tcctgaagcc tgtggagctg cgcttaccac actgtgcgtc 5280 catgactcct gacggtgatc ctaaaacctg gcaaaacaag tgtcttcccg gagatccaaa 5340 ttatctcgtt ggagcaaact gtgtttctgt ccttattgac cacttttaac tcttgaaata 5400 taggaactta aataatgtga aactggatta aacttaatct aaatggaacc actctatcaa 5460 gtattatacc ttttttagag ttgatactac agtttgttag tatgaggcat ttgtttgaac 5520 tgataaagat gagtgagcat gcccctgaac catggtcgga aaacatgcta cacactgcat 5580 gtttgtgatt gacgggactg ttggtattgg ctagaggttc aaagatattt tgctttgtga 5640 tttttgtaat ttttttatcg tcactgctta acttcacata ttgatttccg ttaaaatacc 5700 agccagtaaa tgggggtgca tttgaggtct gttctttcca aagtacactg tttcaaactt 5760 tactatggcc ctggcctagc atacgtacac attttatttt attatgcatg aagtaatatg 5820 cacacatttt ttaaatgcac ctggaatata taaccagtgt tgtggattta acagaaatgt 5880 acagcaagga gatttacaac tgggggaggg tgaagtgaag acaatgactt actgtacatg 5940 aaaacacatt tttcttaggg aaggatacaa aagcatgtga gactggttcc atggcctctt 6000 cagatctcta acttcaccat attaccacag acatactaac cagcagaaat gccttaccct 6060 catgttctta attcttagct cattctcctt gtgttactaa gtttttatgg cttttgtgca 6120 ttatctagat actgtatcat gacaaagact gagtacgttg tgcatttggt ggtttcagaa 6180 atgtgttatc acccagaaga aaatagtggt gtgatttggg gatatttttt tcttttcttt 6240 tcttttcttt tttttttttt ttgacaaggg gcagtggtgg ttttctgttc tttctggcta 6300 tgcatttgaa aattttgatg ttttaaggat gcttgtacat aatgcgtgca taccactttt 6360 gttcttggtt tgtaaattaa cttttataaa ctttaccttt tttatacata aacaagacca 6420 cgtttctaaa ggctaccttt gtattctctc ctgtacctct tgagccttga actttgacct 6480 ctgcagcaat aaagcagcgt ttctatgaca catgcaaggt catttttttt aagaaaaagg 6540 atgcacagag ttgttacatt tttaagtgct gcatttaaaa gatacagtta ctcagaattc 6600 tctagtttga ttaaattctt gcaaagtatc cctactgtaa tttgtgatac aatgctgtgc 6660 cctaaagtgt atttttttac taatagacaa tttattatgg cacatcagca cgatttctgt 6720 ttagataata caccactaca ttctgttaat cattaggtgt gactgaattt cttttgccgt 6780 tattaaaaat ctcaaatttc taaatctcca aaataaaact ttttaaaata aagtgctggc 6840 ttggtctgtt tgcccactgt tttctagttt catgcagctt tataatcctg ttttaaaatc 6900 ctgcacacaa atccctatca cccagcgtca cctaccacct cgtcgtctgg tgttgcatgc 6960 agaatttctc cccttggcca gcatgtacag atgggtgggc agtgctcatc tgaagggctc 7020 agactgaagt ggggcagaag gacctggaga cagagtggga gaaggcagca ggccgacttc 7080 cccctgtggg taaacacaca cccctgcgtg gagaaacacc cctgcatggg gacacacgtg 7140 cgtttgtgtg tgtgcgtgta accatttgta tatggtttta ttccccagat aaatagcacg 7200 ggcattgttt aatgtcaccc acatttgggg gaagaaaatg ggtttagtga gcataaatat 7260 tccattgtgg acatcctact tacttaactg ccacccctgt tgacatttgg attattgcta 7320 tagtgtttca gtaaacacct ttgtggactg aatccatcta tgtggatttt atttttttca 7380 tctttgttaa ggtataattt acatagagta agttactgtt tttaaaatgt atagttcaaa 7440 ttttgacaaa cacatactgt ttatttacca cggttaatac atacaacagt ttctttatct 7500 tctctaatca tttgtacccc tttatactca acccttcttc cagcccctgg caggatgatc 7560 tcttctgttt ctatagttgc ctttttgaca gtgtcatata aatggaatca tacaataaaa 7620 aaaaaaaaaa aaaaaaaa 7638 <![CDATA[<210> 116]]> <![CDATA[<211> 7936]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 116]]> gtggccgctg agttgccggc gccggctgag ccagcggacg ccgcgttcct tggcggccgc 60 cggttcccgg gaagttacgt ggcgaagccg gcttccgagg agacgccggg aggccacggg 120 tgctgctgac gggcgggcga ccgggcgagg ccgacgtggc cgggctgcga aagctgcggg 180 aggccgagtg ggtggccgcg ctcggaggga ggtgccggtc gggcgcgccc cgtggagaag 240 acccgggcgg ggcgggcgct tcccggactt ttgtccgagt tgaattccct ccccctgggc 300 cgggcccttc cggccgcccc cgcccgtgcc ccgctcgctc tcgggagatg tttatttggg 360 ctgtggcgtg aggagcgggc gggccagcgc cgcggagttt cgggtccgag gagcctcgcg 420 cggcgctgga gagagacaag atgtccgcca gagctgcggc cgccaagagc acagcaatgg 480 aggaaacagc tatatgggaa caacatacag tgacgcttca cagggctcct ggatttggat 540 ttggaattgc aatatctggt ggacgagata atcctcattt tcagagtggg gaaacgtcaa 600 tagtgatttc agatgtgctg aaaggaggac cagctgaagg acagctacag gaaaatgacc 660 gagttgcaat ggttaacgga gtttcaatgg ataatgttga acatgctttt gctgttcagc 720 aactaaggaa aagtgggaaa aatgcaaaaa ttacaattag aaggaagaag aaagttcaaa 780 taccagtaag tcgtcctgat cctgaaccag tatctgataa tgaagaagat agttatgatg 840 aggaaataca tgatccaaga agtggccgga gtggtgtggt taacagaagg agtgagaaga 900 tttggccgag ggatagaagt gcaagtagag agaggagctt gtccccgcgg tcagacaggc 960 ggtcagtggc ttccagccag cctgctaaac ctactaaagt cacactggtg aaatcccgga 1020 aaaatgaaga atatggtctt cgattggcaa gccatatatt tgttaaggaa atttcacaag 1080 atagtttggc agcaagagat ggcaatattc aagaaggtga tgttgtattg aagataaatg 1140 gtactgtgac agaaaatatg tcattgacag atgcaaagac attgatagaa aggtctaaag 1200 gcaaattaaa aatggtagtt caaagagatg aacgggctac gctattgaat gtccctgatc 1260 tttctgacag catccactct gctaatgcct ctgagagaga cgacatttca gaaattcagt 1320 cactggcatc agatcattct ggtcgatcac acgataggcc tccccgccgc agccggtcac 1380 gatctcctga ccagcggtca gagccttctg atcattccag gcactcgccg cagcagccaa 1440 gcaatggcag tctccggagt agagatgaag agagaatttc taaacctggg gctgtctcaa 1500 ctcctgtaaa gcatgctgat gatcacacac ctaaaacagt ggaagaagtt acagttgaaa 1560 gaaatgagaa acaaacacct tctcttccag aaccaaagcc tgtgtatgcc caagttgggc 1620 aaccagatgt ggatttacct gtcagtccat ctgatggtgt cctacctaat tcaactcatg 1680 aagatgggat tcttcggccc agcatgaaat tggtaaaatt cagaaaagga gatagtgtgg 1740 gtttgcggct ggctggtgga aatgatgttg gaatatttgt agctggcgtt ctagaagata 1800 gccctgcagc caaggaaggc ttagaggaag gtgatcaaat tctcagggta aacaacgtag 1860 attttacaaa tatcataaga gaagaagccg tccttttcct gcttgacctc cctaaaggag 1920 aagaagtgac catattggct cagaagaaga aggatgttta tcgtcgcatt gtagaatcag 1980 atgtaggaga ttctttctat attagaaccc attttgaata tgaaaaggaa tctccctatg 2040 gacttagttt taacaaagga gaggtgttcc gtgttgtgga taccttgtac aatggaaaac 2100 tgggctcttg gcttgctatt cgaattggta aaaatcataa ggaggtagaa cgaggcatca 2160 tccctaataa gaacagagct gagcagctag ccagtgtaca gtatacactt ccaaaaacag 2220 caggcggaga ccgtgctgac ttctggagat tcagaggtct tcgcagctcc aagagaaatc 2280 ttcgaaaaag cagagaggat ttgtccgctc agcctgttca aacaaagttt ccagcttatg 2340 aaagagtggt tcttcgagaa gctggatttc tgaggcctgt aaccattttt ggaccaatag 2400 ctgatgttgc cagagaaaag ctggcaagag aagaaccaga tatttatcaa attgcaaaga 2460 gtgaaccacg agacgctgga actgaccaac gtagctctgg cattattcgc ctgcatacaa 2520 taaagcaaat catagatcaa gacaaacatg ctttattaga tgtaacacca aatgcagttg 2580 atcgtcttaa ctatgcccag tggtatccaa ttgttgtatt tcttaaccct gattctaagc 2640 aaggagtaaa aacaatgaga atgaggttat gtccagaatc tcggaaaagt gccaggaagt 2700 tatacgagcg atctcataaa cttcgtaaaa ataatcacca tctttttaca actacaatta 2760 acttaaattc aatgaatgat ggttggtatg gtgcgctgaa agaagcaatt caacaacagc 2820 aaaaccagct ggtatgggtt tccgagggaa aggcggatgg tgctacaagt gatgaccttg 2880 atttgcatga tgatcgtctg tcctacctgt cagctccagg tagtgaatac tcaatgtata 2940 gcacggacag tagacacact tctgactatg aagacacaga cacagaaggc ggggcctaca 3000 ctgatcaaga actagatgaa actcttaatg atgaggttgg gactccaccg gagtctgcca 3060 ttacacggtc ctctgagcct gtaagagagg actcctctgg aatgcatcat gaaaaccaaa 3120 catatcctcc ttactcacca caagcgcagc cacaaccaat tcatagaata gactcccctg 3180 gatttaagcc agcctctcaa cagaaagcag aagcttcatc tccagtccct tacctttcgc 3240 ctgaaacaaa cccagcatca tcaacctctg ctgttaatca taatgtaaat ttaactaatg 3300 tcagactgga ggagcccacc ccagctcctt ccacctctta ctcaccacaa gctgattctt 3360 taagaacacc aagtactgag gcagctcaca taatgctaag agatcaagaa ccatcattgt 3420 cgtcgcatgt agatccaaca aaggtgtata gaaaggatcc atatcccgag gaaatgatga 3480 ggcagaacca tgttttgaaa cagccagccg ttagtcaccc agggcacagg ccagacaaag 3540 agcctaatct gacctatgaa ccccaactcc catacgtaga gaaacaagcc agcagagacc 3600 tcgagcagcc cacatacaga tacgagtcct caagctatac ggaccagttt tctcgaaact 3660 atgaacatcg tctgcgatac gaagatcgcg tccccatgta tgaagaacag tggtcatatt 3720 atgatgacaa acagccctac ccatctcggc caccttttga taatcagcac tctcaagacc 3780 ttgactccag acagcatccc gaagagtcct cagaacgagg gtactttcca cgttttgaag 3840 agccagcccc tctgtcttac gacagcagac cacgttacga acaggcacct agagcatccg 3900 ccctgcggca cgaagagcag ccagctcctg ggtatgacac acatggtaga ctcagaccgg 3960 aagcccagcc ccacccttca gcagggccca agcctgcaga gtccaagcag tattttgagc 4020 aatattcacg cagttacgag caagtaccac cccaaggatt tacctctaga gcaggtcatt 4080 ttgagcctct ccatggtgct gcagctgtcc ctccgctgat accttcatct cagcataagc 4140 cagaagctct gccttcaaac accaaaccac tgcctccacc cccaactcaa accgaagaag 4200 aggaagatcc agcaatgaag ccacagtctg tactcaccag agttaagatg tttgaaaaca 4260 aaagatctgc atccttagag accaagaagg atgtaaatga cactggcagt tttaagcctc 4320 cagaagtagc atctaaacct tcaggtgctc ccatcattgg tcccaaaccc acttctcaga 4380 atcaattcag tgaacatgac aaaactctgt acaggatccc agaacctcaa aaacctcaac 4440 tgaagccacc tgaagatatt gttcggtcca atcattatga ccctgaagaa gatgaagaat 4500 attatcgaaa acagctgtca tactttgacc gaagaagttt tgagaataag cctcctgcac 4560 acattgccgc cagccatctc tccgagcctg caaagccagc gcattctcag aatcaatcaa 4620 atttttctag ttattcttca aagggaaagc ctcctgaagc tgatggtgtg gatagatcat 4680 ttggcgagaa acgctatgaa cccatccagg ccactccccc tcctcctcca ttgccctcgc 4740 agtatgccca gccatctcag cctgtcacca gcgcgtctct ccacatacat tctaagggag 4800 cacatggtga aggtaattca gtgtcattgg attttcagaa ttccttagtg tccaaaccag 4860 acccacctcc atctcagaat aagccagcaa ctttcagacc accaaaccga gaagatactg 4920 ctcaggcagc tttctatccc cagaaaagtt ttccagataa agccccagtt aatggaactg 4980 aacagactca gaaaacagtc actccagcat acaatcgatt cacaccaaaa ccatatacaa 5040 gttctgcccg accatttgaa cgcaagtttg aaagtcctaa attcaatcac aatcttctgc 5100 caagtgaaac tgcacataaa cctgacttgt cttcaaaaac tcccacttct ccaaaaactc 5160 ttgtgaaatc gcacagtttg gcacagcctc ctgagtttga cagtggagtt gaaactttct 5220 ctatccatgc agagaagcct aaatatcaaa taaataatat cagcacagtg cctaaagcta 5280 ttcctgtgag tccttcagct gtggaagagg atgaagatga agatggtcat actgtggtgg 5340 ccacagcccg aggcatattt aacagcaatg ggggcgtgct gagttccata gaaactggtg 5400 ttagtataat tatccctcaa ggagccattc ccgaaggagt tgagcaggaa atctatttca 5460 aggtctgccg ggacaacagc atccttccac ctttagataa agagaaaggt gaaacactgc 5520 tgagtccttt ggtgatgtgt ggtccccatg gcctcaagtt cctgaagcct gtggagctgc 5580 gcttaccaca ctgtgcgtcc atgactcctg acggtgatcc taaaacctgg caaaacaagt 5640 gtcttcccgg agatccaaat tatctcgttg gagcaaactg tgtttctgtc cttattgacc 5700 acttttaact cttgaaatat aggaacttaa ataatgtgaa actggattaa acttaatcta 5760 aatggaacca ctctatcaag tattatacct tttttagagt tgatactaca gtttgttagt 5820 atgaggcatt tgtttgaact gataaagatg agtgagcatg cccctgaacc atggtcggaa 5880 aacatgctac acactgcatg tttgtgattg acgggactgt tggtattggc tagaggttca 5940 aagatatttt gctttgtgat ttttgtaatt tttttatcgt cactgcttaa cttcacatat 6000 tgatttccgt taaaatacca gccagtaaat gggggtgcat ttgaggtctg ttctttccaa 6060 agtacactgt ttcaaacttt actatggccc tggcctagca tacgtacaca ttttatttta 6120 ttatgcatga agtaatatgc acacattttt taaatgcacc tggaatatat aaccagtgtt 6180 gtggatttaa cagaaatgta cagcaaggag atttacaact gggggagggt gaagtgaaga 6240 caatgactta ctgtacatga aaacacattt ttcttaggga aggatacaaa agcatgtgag 6300 actggttcca tggcctcttc agatctctaa cttcaccata ttaccacaga catactaacc 6360 agcagaaatg ccttaccctc atgttcttaa ttcttagctc attctccttg tgttactaag 6420 tttttatggc ttttgtgcat tatctagata ctgtatcatg acaaagactg agtacgttgt 6480 gcatttggtg gtttcagaaa tgtgttatca cccagaagaa aatagtggtg tgatttgggg 6540 atattttttt cttttctttt cttttctttt tttttttttt tgacaagggg cagtggtggt 6600 tttctgttct ttctggctat gcatttgaaa attttgatgt tttaaggatg cttgtacata 6660 atgcgtgcat accacttttg ttcttggttt gtaaattaac ttttataaac tttacctttt 6720 ttatacataa acaagaccac gtttctaaag gctacctttg tattctctcc tgtacctctt 6780 gagccttgaa ctttgacctc tgcagcaata aagcagcgtt tctatgacac atgcaaggtc 6840 atttttttta agaaaaagga tgcacagagt tgttacattt ttaagtgctg catttaaaag 6900 atacagttac tcagaattct ctagtttgat taaattcttg caaagtatcc ctactgtaat 6960 ttgtgataca atgctgtgcc ctaaagtgta tttttttact aatagacaat ttattatggc 7020 acatcagcac gatttctgtt tagataatac accactacat tctgttaatc attaggtgtg 7080 actgaatttc ttttgccgtt attaaaaatc tcaaatttct aaatctccaa aataaaactt 7140 tttaaaataa agtgctggct tggtctgttt gcccactgtt ttctagtttc atgcagcttt 7200 ataatcctgt tttaaaatcc tgcacacaaa tccctatcac ccagcgtcac ctaccacctc 7260 gtcgtctggt gttgcatgca gaatttctcc ccttggccag catgtacaga tgggtgggca 7320 gtgctcatct gaagggctca gactgaagtg gggcagaagg acctggagac agagtgggag 7380 aaggcagcag gccgacttcc ccctgtgggt aaacacacac ccctgcgtgg agaaacaccc 7440 ctgcatgggg acacacgtgc gtttgtgtgt gtgcgtgtaa ccatttgtat atggttttat 7500 tccccagata aatagcacgg gcattgttta atgtcaccca catttggggg aagaaaatgg 7560 gtttagtgag cataaatatt ccattgtgga catcctactt acttaactgc cacccctgtt 7620 gacatttgga ttattgctat agtgtttcag taaacacctt tgtggactga atccatctat 7680 gtggatttta tttttttcat ctttgttaag gtataattta catagagtaa gttactgttt 7740 ttaaaatgta tagttcaaat tttgacaaac acatactgtt tatttaccac ggttaataca 7800 tacaacagtt tctttatctt ctctaatcat ttgtacccct ttatactcaa cccttcttcc 7860 agcccctggc aggatgatct cttctgtttc tatagttgcc tttttgacag tgtcatataa 7920 atggaatcat acaata 7936 <![CDATA[<210> 117]]> <![CDATA[<211> 7735]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 117]]> gtggccgctg agttgccggc gccggctgag ccagcggacg ccgcgttcct tggcggccgc 60 cggttcccgg gaagttacgt ggcgaagccg gcttccgagg agacgccggg aggccacggg 120 tgctgctgac gggcgggcga ccgggcgagg ccgacgtggc cgggctgcga aagctgcggg 180 aggccgagtg ggtggccgcg ctcggaggga ggtgccggtc gggcgcgccc cgtggagaag 240 acccgggcgg ggcgggcgct tcccggactt ttgtccgagt tgaattccct ccccctgggc 300 cgggcccttc cggccgcccc cgcccgtgcc ccgctcgctc tcgggagatg tttatttggg 360 ctgtggcgtg aggagcgggc gggccagcgc cgcggagttt cgggtccgag gagcctcgcg 420 cggcgctgga gagagacaag atgtccgcca gagctgcggc cgccaagagc acagcaatgg 480 aggaaacagc tatatgggaa caacatacag tgacgcttca cagggctcct ggatttggat 540 ttggaattgc aatatctggt ggacgagata atcctcattt tcagagtggg gaaacgtcaa 600 tagtgatttc agatgtgctg aaaggaggac cagctgaagg acagctacag gaaaatgacc 660 gagttgcaat ggttaacgga gtttcaatgg ataatgttga acatgctttt gctgttcagc 720 aactaaggaa aagtgggaaa aatgcaaaaa ttacaattag aaggaagaag aaagttcaaa 780 taccagtaag tcgtcctgat cctgaaccag tatctgataa tgaagaagat agttatgatg 840 aggaaataca tgatccaaga agtggccgga gtggtgtggt taacagaagg agtgagaaga 900 tttggccgag ggatagaagt gcaagtagag agaggagctt gtccccgcgg tcagacaggc 960 ggtcagtggc ttccagccag cctgctaaac ctactaaagt cacactggtg aaatcccgga 1020 aaaatgaaga atatggtctt cgattggcaa gccatatatt tgttaaggaa atttcacaag 1080 atagtttggc agcaagagat ggcaatattc aagaaggtga tgttgtattg aagataaatg 1140 gtactgtgac agaaaatatg tcattgacag atgcaaagac attgatagaa aggtctaaag 1200 gcaaattaaa aatggtagtt caaagagatg aacgggctac gctattgaat gtccctgatc 1260 tttctgacag catccactct gctaatgcct ctgagagaga cgacatttca gaaattcagt 1320 cactggcatc agatcattct ggtcgatcac acgataggcc tccccgccgc agccggtcac 1380 gatctcctga ccagcggtca gagccttctg atcattccag gcactcgccg cagcagccaa 1440 gcaatggcag tctccggagt agagatgaag agagaatttc taaacctggg gctgtctcaa 1500 ctcctgtaaa gcatgctgat gatcacacac ctaaaacagt ggaagaagtt acagttgaaa 1560 gaaatgagaa acaaacacct tctcttccag aaccaaagcc tgtgtatgcc caagttgggc 1620 aaccagatgt ggatttacct gtcagtccat ctgatggtgt cctacctaat tcaactcatg 1680 aagatgggat tcttcggccc agcatgaaat tggtaaaatt cagaaaagga gatagtgtgg 1740 gtttgcggct ggctggtgga aatgatgttg gaatatttgt agctggcgtt ctagaagata 1800 gccctgcagc caaggaaggc ttagaggaag gtgatcaaat tctcagggta aacaacgtag 1860 attttacaaa tatcataaga gaagaagccg tccttttcct gcttgacctc cctaaaggag 1920 aagaagtgac catattggct cagaagaaga aggatgttta tcgtcgcatt gtagaatcag 1980 atgtaggaga ttctttctat attagaaccc attttgaata tgaaaaggaa tctccctatg 2040 gacttagttt taacaaagga gaggtgttcc gtgttgtgga taccttgtac aatggaaaac 2100 tgggctcttg gcttgctatt cgaattggta aaaatcataa ggaggtagaa cgaggcatca 2160 tccctaataa gaacagagct gagcagctag ccagtgtaca gtatacactt ccaaaaacag 2220 caggcggaga ccgtgctgac ttctggagat tcagaggtct tcgcagctcc aagagaaatc 2280 ttcgaaaaag cagagaggat ttgtccgctc agcctgttca aacaaagttt ccagcttatg 2340 aaagagtggt tcttcgagaa gctggatttc tgaggcctgt aaccattttt ggaccaatag 2400 ctgatgttgc cagagaaaag ctggcaagag aagaaccaga tatttatcaa attgcaaaga 2460 gtgaaccacg agacgctgga actgaccaac gtagctctgg cattattcgc ctgcatacaa 2520 taaagcaaat catagatcaa gacaaacatg ctttattaga tgtaacacca aatgcagttg 2580 atcgtcttaa ctatgcccag tggtatccaa ttgttgtatt tcttaaccct gattctaagc 2640 aaggagtaaa aacaatgaga atgaggttat gtccagaatc tcggaaaagt gccaggaagt 2700 tatacgagcg atctcataaa cttcgtaaaa ataatcacca tctttttaca actacaatta 2760 acttaaattc aatgaatgat ggttggtatg gtgcgctgaa agaagcaatt caacaacagc 2820 aaaaccagct ggtatgggtt tccgagggaa aggcggatgg tgctacaagt gatgaccttg 2880 atttgcatga tgatcgtctg tcctacctgt cagctccagg tagtgaatac tcaatgtata 2940 gcacggacag tagacacact tctgactatg aagacacaga cacagaaggc ggggcctaca 3000 ctgatcaaga actagatgaa actcttaatg atgaggttgg gactccaccg gagtctgcca 3060 ttacacggtc ctctgagcct gtaagagagg actcctctgg aatgcatcat gaaaaccaaa 3120 catatcctcc ttactcacca caagcgcagc cacaaccaat tcatagaata gactcccctg 3180 gatttaagcc agcctctcaa caggtgtata gaaaggatcc atatcccgag gaaatgatga 3240 ggcagaacca tgttttgaaa cagccagccg ttagtcaccc agggcacagg ccagacaaag 3300 agcctaatct gacctatgaa ccccaactcc catacgtaga gaaacaagcc agcagagacc 3360 tcgagcagcc cacatacaga tacgagtcct caagctatac ggaccagttt tctcgaaact 3420 atgaacatcg tctgcgatac gaagatcgcg tccccatgta tgaagaacag tggtcatatt 3480 atgatgacaa acagccctac ccatctcggc caccttttga taatcagcac tctcaagacc 3540 ttgactccag acagcatccc gaagagtcct cagaacgagg gtactttcca cgttttgaag 3600 agccagcccc tctgtcttac gacagcagac cacgttacga acaggcacct agagcatccg 3660 ccctgcggca cgaagagcag ccagctcctg ggtatgacac acatggtaga ctcagaccgg 3720 aagcccagcc ccacccttca gcagggccca agcctgcaga gtccaagcag tattttgagc 3780 aatattcacg cagttacgag caagtaccac cccaaggatt tacctctaga gcaggtcatt 3840 ttgagcctct ccatggtgct gcagctgtcc ctccgctgat accttcatct cagcataagc 3900 cagaagctct gccttcaaac accaaaccac tgcctccacc cccaactcaa accgaagaag 3960 aggaagatcc agcaatgaag ccacagtctg tactcaccag agttaagatg tttgaaaaca 4020 aaagatctgc atccttagag accaagaagg atgtaaatga cactggcagt tttaagcctc 4080 cagaagtagc atctaaacct tcaggtgctc ccatcattgg tcccaaaccc acttctcaga 4140 atcaattcag tgaacatgac aaaactctgt acaggatccc agaacctcaa aaacctcaac 4200 tgaagccacc tgaagatatt gttcggtcca atcattatga ccctgaagaa gatgaagaat 4260 attatcgaaa acagctgtca tactttgacc gaagaagttt tgagaataag cctcctgcac 4320 acattgccgc cagccatctc tccgagcctg caaagccagc gcattctcag aatcaatcaa 4380 atttttctag ttattcttca aagggaaagc ctcctgaagc tgatggtgtg gatagatcat 4440 ttggcgagaa acgctatgaa cccatccagg ccactccccc tcctcctcca ttgccctcgc 4500 agtatgccca gccatctcag cctgtcacca gcgcgtctct ccacatacat tctaagggag 4560 cacatggtga aggtaattca gtgtcattgg attttcagaa ttccttagtg tccaaaccag 4620 acccacctcc atctcagaat aagccagcaa ctttcagacc accaaaccga gaagatactg 4680 ctcaggcagc tttctatccc cagaaaagtt ttccagataa agccccagtt aatggaactg 4740 aacagactca gaaaacagtc actccagcat acaatcgatt cacaccaaaa ccatatacaa 4800 gttctgcccg accatttgaa cgcaagtttg aaagtcctaa attcaatcac aatcttctgc 4860 caagtgaaac tgcacataaa cctgacttgt cttcaaaaac tcccacttct ccaaaaactc 4920 ttgtgaaatc gcacagtttg gcacagcctc ctgagtttga cagtggagtt gaaactttct 4980 ctatccatgc agagaagcct aaatatcaaa taaataatat cagcacagtg cctaaagcta 5040 ttcctgtgag tccttcagct gtggaagagg atgaagatga agatggtcat actgtggtgg 5100 ccacagcccg aggcatattt aacagcaatg ggggcgtgct gagttccata gaaactggtg 5160 ttagtataat tatccctcaa ggagccattc ccgaaggagt tgagcaggaa atctatttca 5220 aggtctgccg ggacaacagc atccttccac ctttagataa agagaaaggt gaaacactgc 5280 tgagtccttt ggtgatgtgt ggtccccatg gcctcaagtt cctgaagcct gtggagctgc 5340 gcttaccaca ctgtgcgtcc atgactcctg acggttggtc ttttgctcta aaatcatccg 5400 actcctcgtc gggtgatcct aaaacctggc aaaacaagtg tcttcccgga gatccaaatt 5460 atctcgttgg agcaaactgt gtttctgtcc ttattgacca cttttaactc ttgaaatata 5520 ggaacttaaa taatgtgaaa ctggattaaa cttaatctaa atggaaccac tctatcaagt 5580 attatacctt ttttagagtt gatactacag tttgttagta tgaggcattt gtttgaactg 5640 ataaagatga gtgagcatgc ccctgaacca tggtcggaaa acatgctaca cactgcatgt 5700 ttgtgattga cgggactgtt ggtattggct agaggttcaa agatattttg ctttgtgatt 5760 tttgtaattt ttttatcgtc actgcttaac ttcacatatt gatttccgtt aaaataccag 5820 ccagtaaatg ggggtgcatt tgaggtctgt tctttccaaa gtacactgtt tcaaacttta 5880 ctatggccct ggcctagcat acgtacacat tttattttat tatgcatgaa gtaatatgca 5940 cacatttttt aaatgcacct ggaatatata accagtgttg tggatttaac agaaatgtac 6000 agcaaggaga tttacaactg ggggagggtg aagtgaagac aatgacttac tgtacatgaa 6060 aacacatttt tcttagggaa ggatacaaaa gcatgtgaga ctggttccat ggcctcttca 6120 gatctctaac ttcaccatat taccacagac atactaacca gcagaaatgc cttaccctca 6180 tgttcttaat tcttagctca ttctccttgt gttactaagt ttttatggct tttgtgcatt 6240 atctagatac tgtatcatga caaagactga gtacgttgtg catttggtgg tttcagaaat 6300 gtgttatcac ccagaagaaa atagtggtgt gatttgggga tatttttttc ttttcttttc 6360 ttttcttttt tttttttttt gacaaggggc agtggtggtt ttctgttctt tctggctatg 6420 catttgaaaa ttttgatgtt ttaaggatgc ttgtacataa tgcgtgcata ccacttttgt 6480 tcttggtttg taaattaact tttataaact ttaccttttt tatacataaa caagaccacg 6540 tttctaaagg ctacctttgt attctctcct gtacctcttg agccttgaac tttgacctct 6600 gcagcaataa agcagcgttt ctatgacaca tgcaaggtca ttttttttaa gaaaaaggat 6660 gcacagagtt gttacatttt taagtgctgc atttaaaaga tacagttact cagaattctc 6720 tagtttgatt aaattcttgc aaagtatccc tactgtaatt tgtgatacaa tgctgtgccc 6780 taaagtgtat ttttttacta atagacaatt tattatggca catcagcacg atttctgttt 6840 agataataca ccactacatt ctgttaatca ttaggtgtga ctgaatttct tttgccgtta 6900 ttaaaaatct caaatttcta aatctccaaa ataaaacttt ttaaaataaa gtgctggctt 6960 ggtctgtttg cccactgttt tctagtttca tgcagcttta taatcctgtt ttaaaatcct 7020 gcacacaaat ccctatcacc cagcgtcacc taccacctcg tcgtctggtg ttgcatgcag 7080 aatttctccc cttggccagc atgtacagat gggtgggcag tgctcatctg aagggctcag 7140 actgaagtgg ggcagaagga cctggagaca gagtgggaga aggcagcagg ccgacttccc 7200 cctgtgggta aacacacacc cctgcgtgga gaaacacccc tgcatgggga cacacgtgcg 7260 tttgtgtgtg tgcgtgtaac catttgtata tggttttatt ccccagataa atagcacggg 7320 cattgtttaa tgtcacccac atttggggga agaaaatggg tttagtgagc ataaatattc 7380 cattgtggac atcctactta cttaactgcc acccctgttg acatttggat tattgctata 7440 gtgtttcagt aaacaccttt gtggactgaa tccatctatg tggattttat ttttttcatc 7500 tttgttaagg tataatttac atagagtaag ttactgtttt taaaatgtat agttcaaatt 7560 ttgacaaaca catactgttt atttaccacg gttaatacat acaacagttt ctttatcttc 7620 tctaatcatt tgtacccctt tatactcaac ccttcttcca gcccctggca ggatgatctc 7680 ttctgtttct atagttgcct ttttgacagt gtcatataaa tggaatcata caata 7735 <![CDATA[<210> 118]]> <![CDATA[<211> 7915]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 118]]> gtggccgctg agttgccggc gccggctgag ccagcggacg ccgcgttcct tggcggccgc 60 cggttcccgg gaagttacgt ggcgaagccg gcttccgagg agacgccggg aggccacggg 120 tgctgctgac gggcgggcga ccgggcgagg ccgacgtggc cgggctgcga aagctgcggg 180 aggccgagtg ggtggccgcg ctcggaggga ggtgccggtc gggcgcgccc cgtggagaag 240 acccgggcgg ggcgggcgct tcccggactt ttgtccgagt tgaattccct ccccctgggc 300 cgggcccttc cggccgcccc cgcccgtgcc ccgctcgctc tcgggagatg tttatttggg 360 ctgtggcgtg aggagcgggc gggccagcgc cgcggagttt cgggtccgag gagcctcgcg 420 cggcgctgga gagagacaag atgtccgcca gagctgcggc cgccaagagc acagcaatgg 480 aggaaacagc tatatgggaa caacatacag tgacgcttca cagggctcct ggatttggat 540 ttggaattgc aatatctggt ggacgagata atcctcattt tcagagtggg gaaacgtcaa 600 tagtgatttc agatgtgctg aaaggaggac cagctgaagg acagctacag gaaaatgacc 660 gagttgcaat ggttaacgga gtttcaatgg ataatgttga acatgctttt gctgttcagc 720 aactaaggaa aagtgggaaa aatgcaaaaa ttacaattag aaggaagaag aaagttcaaa 780 taccagtaag tcgtcctgat cctgaaccag tatctgataa tgaagaagat agttatgatg 840 aggaaataca tgatccaaga agtggccgga gtggtgtggt taacagaagg agtgagaaga 900 tttggccgag ggatagaagt gcaagtagag agaggagctt gtccccgcgg tcagacaggc 960 ggtcagtggc ttccagccag cctgctaaac ctactaaagt cacactggtg aaatcccgga 1020 aaaatgaaga atatggtctt cgattggcaa gccatatatt tgttaaggaa atttcacaag 1080 atagtttggc agcaagagat ggcaatattc aagaaggtga tgttgtattg aagataaatg 1140 gtactgtgac agaaaatatg tcattgacag atgcaaagac attgatagaa aggtctaaag 1200 gcaaattaaa aatggtagtt caaagagatg aacgggctac gctattgaat gtccctgatc 1260 tttctgacag catccactct gctaatgcct ctgagagaga cgacatttca gaaattcagt 1320 cactggcatc agatcattct ggtcgatcac acgataggcc tccccgccgc agccggtcac 1380 gatctcctga ccagcggtca gagccttctg atcattccag gcactcgccg cagcagccaa 1440 gcaatggcag tctccggagt agagatgaag agagaatttc taaacctggg gctgtctcaa 1500 ctcctgtaaa gcatgctgat gatcacacac ctaaaacagt ggaagaagtt acagttgaaa 1560 gaaatgagaa acaaacacct tctcttccag aaccaaagcc tgtgtatgcc caagttgggc 1620 aaccagatgt ggatttacct gtcagtccat ctgatggtgt cctacctaat tcaactcatg 1680 aagatgggat tcttcggccc agcatgaaat tggtaaaatt cagaaaagga gatagtgtgg 1740 gtttgcggct ggctggtgga aatgatgttg gaatatttgt agctggcgtt ctagaagata 1800 gccctgcagc caaggaaggc ttagaggaag gtgatcaaat tctcagggta aacaacgtag 1860 attttacaaa tatcataaga gaagaagccg tccttttcct gcttgacctc cctaaaggag 1920 aagaagtgac catattggct cagaagaaga aggatgttta tcgtcgcatt gtagaatcag 1980 atgtaggaga ttctttctat attagaaccc attttgaata tgaaaaggaa tctccctatg 2040 gacttagttt taacaaagga gaggtgttcc gtgttgtgga taccttgtac aatggaaaac 2100 tgggctcttg gcttgctatt cgaattggta aaaatcataa ggaggtagaa cgaggcatca 2160 tccctaataa gaacagagct gagcagctag ccagtgtaca gtatacactt ccaaaaacag 2220 caggcggaga ccgtgctgac ttctggagat tcagaggtct tcgcagctcc aagagaaatc 2280 ttcgaaaaag cagagaggat ttgtccgctc agcctgttca aacaaagttt ccagcttatg 2340 aaagagtggt tcttcgagaa gctggatttc tgaggcctgt aaccattttt ggaccaatag 2400 ctgatgttgc cagagaaaag ctggcaagag aagaaccaga tatttatcaa attgcaaaga 2460 gtgaaccacg agacgctgga actgaccaac gtagctctgg cattattcgc ctgcatacaa 2520 taaagcaaat catagatcaa gacaaacatg ctttattaga tgtaacacca aatgcagttg 2580 atcgtcttaa ctatgcccag tggtatccaa ttgttgtatt tcttaaccct gattctaagc 2640 aaggagtaaa aacaatgaga atgaggttat gtccagaatc tcggaaaagt gccaggaagt 2700 tatacgagcg atctcataaa cttcgtaaaa ataatcacca tctttttaca actacaatta 2760 acttaaattc aatgaatgat ggttggtatg gtgcgctgaa agaagcaatt caacaacagc 2820 aaaaccagct ggtatgggtt tccgagggaa aggcggatgg tgctacaagt gatgaccttg 2880 atttgcatga tgatcgtctg tcctacctgt cagctccagg tagtgaatac tcaatgtata 2940 gcacggacag tagacacact tctgactatg aagacacaga cacagaaggc ggggcctaca 3000 ctgatcaaga actagatgaa actcttaatg atgaggttgg gactccaccg gagtctgcca 3060 ttacacggtc ctctgagcct gtaagagagg actcctctgg aatgcatcat gaaaaccaaa 3120 catatcctcc ttactcacca caagcgcagc cacaaccaat tcatagaata gactcccctg 3180 gatttaagcc agcctctcaa cagaaagcag aagcttcatc tccagtccct tacctttcgc 3240 ctgaaacaaa cccagcatca tcaacctctg ctgttaatca taatgtaaat ttaactaatg 3300 tcagactgga ggagcccacc ccagctcctt ccacctctta ctcaccacaa gctgattctt 3360 taagaacacc aagtactgag gcagctcaca taatgctaag agatcaagaa ccatcattgt 3420 cgtcgcatgt agatccaaca aaggtgtata gaaaggatcc atatcccgag gaaatgatga 3480 ggcagaacca tgttttgaaa cagccagccg ttagtcaccc agggcacagg ccagacaaag 3540 agcctaatct gacctatgaa ccccaactcc catacgtaga gaaacaagcc agcagagacc 3600 tcgagcagcc cacatacaga tacgagtcct caagctatac ggaccagttt tctcgaaact 3660 atgaacatcg tctgcgatac gaagatcgcg tccccatgta tgaagaacag tggtcatatt 3720 atgatgacaa acagccctac ccatctcggc caccttttga taatcagcac tctcaagacc 3780 ttgactccag acagcatccc gaagagtcct cagaacgagg gtactttcca cgttttgaag 3840 agccagcccc tctgtcttac gacagcagac cacgttacga acaggcacct agagcatccg 3900 ccctgcggca cgaagagcag ccagctcctg ggtatgacac acatggtaga ctcagaccgg 3960 aagcccagcc ccacccttca gcagggccca agcctgcaga gtccaagcag tattttgagc 4020 aatattcacg cagttacgag caagtaccac cccaaggatt tacctctaga gcaggtcatt 4080 ttgagcctct ccatggtgct gcagctgtcc ctccgctgat accttcatct cagcataagc 4140 cagaagctct gccttcaaac accaaaccac tgcctccacc cccaactcaa accgaagaag 4200 aggaagatcc agcaatgaag ccacagtctg tactcaccag agttaagatg tttgaaaaca 4260 aaagatctgc atccttagag accaagaagg atgtaaatga cactggcagt tttaagcctc 4320 cagaagtagc atctaaacct tcaggtgctc ccatcattgg tcccaaaccc acttctcaga 4380 atcaattcag tgaacatgac aaaactctgt acaggatccc agaacctcaa aaacctcaac 4440 tgaagccacc tgaagatatt gttcggtcca atcattatga ccctgaagaa gatgaagaat 4500 attatcgaaa acagctgtca tactttgacc gaagaagttt tgagaataag cctcctgcac 4560 acattgccgc cagccatctc tccgagcctg caaagccagc gcattctcag aatcaatcaa 4620 atttttctag ttattcttca aagggaaagc ctcctgaagc tgatggtgtg gatagatcat 4680 ttggcgagaa acgctatgaa cccatccagg ccactccccc tcctcctcca ttgccctcgc 4740 agtatgccca gccatctcag cctgtcacca gcgcgtctct ccacatacat tctaagggag 4800 cacatggtga aggtaattca gtgtcattgg attttcagaa ttccttagtg tccaaaccag 4860 acccacctcc atctcagaat aagccagcaa ctttcagacc accaaaccga gaagatactg 4920 ctcaggcagc tttctatccc cagaaaagtt ttccagataa agccccagtt aatggaactg 4980 aacagactca gaaaacagtc actccagcat acaatcgatt cacaccaaaa ccatatacaa 5040 gttctgcccg accatttgaa cgcaagtttg aaagtcctaa attcaatcac aatcttctgc 5100 caagtgaaac tgcacataaa cctgacttgt cttcaaaaac tcccacttct ccaaaaactc 5160 ttgtgaaatc gcacagtttg gcacagcctc ctgagtttga cagtggagtt gaaactttct 5220 ctatccatgc agagaagcct aaatatcaaa taaataatat cagcacagtg cctaaagcta 5280 ttcctgtgag tccttcagct gtggaagagg atgaagatga agatggtcat actgtggtgg 5340 ccacagcccg aggcatattt aacagcaatg ggggcgtgct gagttccata gaaactggtg 5400 ttagtataat tatccctcaa ggagccattc ccgaaggagt tgagcaggaa atctatttca 5460 aggtctgccg ggacaacagc atccttccac ctttagataa agagaaaggt gaaacactgc 5520 tgagtccttt ggtgatgtgt ggtccccatg gcctcaagtt cctgaagcct gtggagctgc 5580 gcttaccaca ctgtgatcct aaaacctggc aaaacaagtg tcttcccgga gatccaaatt 5640 atctcgttgg agcaaactgt gtttctgtcc ttattgacca cttttaactc ttgaaatata 5700 ggaacttaaa taatgtgaaa ctggattaaa cttaatctaa atggaaccac tctatcaagt 5760 attatacctt ttttagagtt gatactacag tttgttagta tgaggcattt gtttgaactg 5820 ataaagatga gtgagcatgc ccctgaacca tggtcggaaa acatgctaca cactgcatgt 5880 ttgtgattga cgggactgtt ggtattggct agaggttcaa agatattttg ctttgtgatt 5940 tttgtaattt ttttatcgtc actgcttaac ttcacatatt gatttccgtt aaaataccag 6000 ccagtaaatg ggggtgcatt tgaggtctgt tctttccaaa gtacactgtt tcaaacttta 6060 ctatggccct ggcctagcat acgtacacat tttattttat tatgcatgaa gtaatatgca 6120 cacatttttt aaatgcacct ggaatatata accagtgttg tggatttaac agaaatgtac 6180 agcaaggaga tttacaactg ggggagggtg aagtgaagac aatgacttac tgtacatgaa 6240 aacacatttt tcttagggaa ggatacaaaa gcatgtgaga ctggttccat ggcctcttca 6300 gatctctaac ttcaccatat taccacagac atactaacca gcagaaatgc cttaccctca 6360 tgttcttaat tcttagctca ttctccttgt gttactaagt ttttatggct tttgtgcatt 6420 atctagatac tgtatcatga caaagactga gtacgttgtg catttggtgg tttcagaaat 6480 gtgttatcac ccagaagaaa atagtggtgt gatttgggga tatttttttc ttttcttttc 6540 ttttcttttt tttttttttt gacaaggggc agtggtggtt ttctgttctt tctggctatg 6600 catttgaaaa ttttgatgtt ttaaggatgc ttgtacataa tgcgtgcata ccacttttgt 6660 tcttggtttg taaattaact tttataaact ttaccttttt tatacataaa caagaccacg 6720 tttctaaagg ctacctttgt attctctcct gtacctcttg agccttgaac tttgacctct 6780 gcagcaataa agcagcgttt ctatgacaca tgcaaggtca ttttttttaa gaaaaaggat 6840 gcacagagtt gttacatttt taagtgctgc atttaaaaga tacagttact cagaattctc 6900 tagtttgatt aaattcttgc aaagtatccc tactgtaatt tgtgatacaa tgctgtgccc 6960 taaagtgtat ttttttacta atagacaatt tattatggca catcagcacg atttctgttt 7020 agataataca ccactacatt ctgttaatca ttaggtgtga ctgaatttct tttgccgtta 7080 ttaaaaatct caaatttcta aatctccaaa ataaaacttt ttaaaataaa gtgctggctt 7140 ggtctgtttg cccactgttt tctagtttca tgcagcttta taatcctgtt ttaaaatcct 7200 gcacacaaat ccctatcacc cagcgtcacc taccacctcg tcgtctggtg ttgcatgcag 7260 aatttctccc cttggccagc atgtacagat gggtgggcag tgctcatctg aagggctcag 7320 actgaagtgg ggcagaagga cctggagaca gagtgggaga aggcagcagg ccgacttccc 7380 cctgtgggta aacacacacc cctgcgtgga gaaacacccc tgcatgggga cacacgtgcg 7440 tttgtgtgtg tgcgtgtaac catttgtata tggttttatt ccccagataa atagcacggg 7500 cattgtttaa tgtcacccac atttggggga agaaaatggg tttagtgagc ataaatattc 7560 cattgtggac atcctactta cttaactgcc acccctgttg acatttggat tattgctata 7620 gtgtttcagt aaacaccttt gtggactgaa tccatctatg tggattttat ttttttcatc 7680 tttgttaagg tataatttac atagagtaag ttactgtttt taaaatgtat agttcaaatt 7740 ttgacaaaca catactgttt atttaccacg gttaatacat acaacagttt ctttatcttc 7800 tctaatcatt tgtacccctt tatactcaac ccttcttcca gcccctggca ggatgatctc 7860 ttctgtttct atagttgcct ttttgacagt gtcatataaa tggaatcata caata 7915 <![CDATA[<210> 119]]> <![CDATA[<211> 7675]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 119]]> gtggccgctg agttgccggc gccggctgag ccagcggacg ccgcgttcct tggcggccgc 60 cggttcccgg gaagttacgt ggcgaagccg gcttccgagg agacgccggg aggccacggg 120 tgctgctgac gggcgggcga ccgggcgagg ccgacgtggc cgggctgcga aagctgcggg 180 aggccgagtg ggtggccgcg ctcggaggga ggtgccggtc gggcgcgccc cgtggagaag 240 acccgggcgg ggcgggcgct tcccggactt ttgtccgagt tgaattccct ccccctgggc 300 cgggcccttc cggccgcccc cgcccgtgcc ccgctcgctc tcgggagatg tttatttggg 360 ctgtggcgtg aggagcgggc gggccagcgc cgcggagttt cgggtccgag gagcctcgcg 420 cggcgctgga gagagacaag atgtccgcca gagctgcggc cgccaagagc acagcaatgg 480 aggaaacagc tatatgggaa caacatacag tgacgcttca cagggctcct ggatttggat 540 ttggaattgc aatatctggt ggacgagata atcctcattt tcagagtggg gaaacgtcaa 600 tagtgatttc agatgtgctg aaaggaggac cagctgaagg acagctacag gaaaatgacc 660 gagttgcaat ggttaacgga gtttcaatgg ataatgttga acatgctttt gctgttcagc 720 aactaaggaa aagtgggaaa aatgcaaaaa ttacaattag aaggaagaag aaagttcaaa 780 taccagtaag tcgtcctgat cctgaaccag tatctgataa tgaagaagat agttatgatg 840 aggaaataca tgatccaaga agtggccgga gtggtgtggt taacagaagg agtgagaaga 900 tttggccgag ggatagaagt gcaagtagag agaggagctt gtccccgcgg tcagacaggc 960 ggtcagtggc ttccagccag cctgctaaac ctactaaagt cacactggtg aaatcccgga 1020 aaaatgaaga atatggtctt cgattggcaa gccatatatt tgttaaggaa atttcacaag 1080 atagtttggc agcaagagat ggcaatattc aagaaggtga tgttgtattg aagataaatg 1140 gtactgtgac agaaaatatg tcattgacag atgcaaagac attgatagaa aggtctaaag 1200 gcaaattaaa aatggtagtt caaagagatg aacgggctac gctattgaat gtccctgatc 1260 tttctgacag catccactct gctaatgcct ctgagagaga cgacatttca gaaattcagt 1320 cactggcatc agatcattct ggtcgatcac acgataggcc tccccgccgc agccggtcac 1380 gatctcctga ccagcggtca gagccttctg atcattccag gcactcgccg cagcagccaa 1440 gcaatggcag tctccggagt agagatgaag agagaatttc taaacctggg gctgtctcaa 1500 ctcctgtaaa gcatgctgat gatcacacac ctaaaacagt ggaagaagtt acagttgaaa 1560 gaaatgagaa acaaacacct tctcttccag aaccaaagcc tgtgtatgcc caagttgggc 1620 aaccagatgt ggatttacct gtcagtccat ctgatggtgt cctacctaat tcaactcatg 1680 aagatgggat tcttcggccc agcatgaaat tggtaaaatt cagaaaagga gatagtgtgg 1740 gtttgcggct ggctggtgga aatgatgttg gaatatttgt agctggcgtt ctagaagata 1800 gccctgcagc caaggaaggc ttagaggaag gtgatcaaat tctcagggta aacaacgtag 1860 attttacaaa tatcataaga gaagaagccg tccttttcct gcttgacctc cctaaaggag 1920 aagaagtgac catattggct cagaagaaga aggatgttta tcgtcgcatt gtagaatcag 1980 atgtaggaga ttctttctat attagaaccc attttgaata tgaaaaggaa tctccctatg 2040 gacttagttt taacaaagga gaggtgttcc gtgttgtgga taccttgtac aatggaaaac 2100 tgggctcttg gcttgctatt cgaattggta aaaatcataa ggaggtagaa cgaggcatca 2160 tccctaataa gaacagagct gagcagctag ccagtgtaca gtatacactt ccaaaaacag 2220 caggcggaga ccgtgctgac ttctggagat tcagaggtct tcgcagctcc aagagaaatc 2280 ttcgaaaaag cagagaggat ttgtccgctc agcctgttca aacaaagttt ccagcttatg 2340 aaagagtggt tcttcgagaa gctggatttc tgaggcctgt aaccattttt ggaccaatag 2400 ctgatgttgc cagagaaaag ctggcaagag aagaaccaga tatttatcaa attgcaaaga 2460 gtgaaccacg agacgctgga actgaccaac gtagctctgg cattattcgc ctgcatacaa 2520 taaagcaaat catagatcaa gacaaacatg ctttattaga tgtaacacca aatgcagttg 2580 atcgtcttaa ctatgcccag tggtatccaa ttgttgtatt tcttaaccct gattctaagc 2640 aaggagtaaa aacaatgaga atgaggttat gtccagaatc tcggaaaagt gccaggaagt 2700 tatacgagcg atctcataaa cttcgtaaaa ataatcacca tctttttaca actacaatta 2760 acttaaattc aatgaatgat ggttggtatg gtgcgctgaa agaagcaatt caacaacagc 2820 aaaaccagct ggtatgggtt tccgagggaa aggcggatgg tgctacaagt gatgaccttg 2880 atttgcatga tgatcgtctg tcctacctgt cagctccagg tagtgaatac tcaatgtata 2940 gcacggacag tagacacact tctgactatg aagacacaga cacagaaggc ggggcctaca 3000 ctgatcaaga actagatgaa actcttaatg atgaggttgg gactccaccg gagtctgcca 3060 ttacacggtc ctctgagcct gtaagagagg actcctctgg aatgcatcat gaaaaccaaa 3120 catatcctcc ttactcacca caagcgcagc cacaaccaat tcatagaata gactcccctg 3180 gatttaagcc agcctctcaa caggtgtata gaaaggatcc atatcccgag gaaatgatga 3240 ggcagaacca tgttttgaaa cagccagccg ttagtcaccc agggcacagg ccagacaaag 3300 agcctaatct gacctatgaa ccccaactcc catacgtaga gaaacaagcc agcagagacc 3360 tcgagcagcc cacatacaga tacgagtcct caagctatac ggaccagttt tctcgaaact 3420 atgaacatcg tctgcgatac gaagatcgcg tccccatgta tgaagaacag tggtcatatt 3480 atgatgacaa acagccctac ccatctcggc caccttttga taatcagcac tctcaagacc 3540 ttgactccag acagcatccc gaagagtcct cagaacgagg gtactttcca cgttttgaag 3600 agccagcccc tctgtcttac gacagcagac cacgttacga acaggcacct agagcatccg 3660 ccctgcggca cgaagagcag ccagctcctg ggtatgacac acatggtaga ctcagaccgg 3720 aagcccagcc ccacccttca gcagggccca agcctgcaga gtccaagcag tattttgagc 3780 aatattcacg cagttacgag caagtaccac cccaaggatt tacctctaga gcaggtcatt 3840 ttgagcctct ccatggtgct gcagctgtcc ctccgctgat accttcatct cagcataagc 3900 cagaagctct gccttcaaac accaaaccac tgcctccacc cccaactcaa accgaagaag 3960 aggaagatcc agcaatgaag ccacagtctg tactcaccag agttaagatg tttgaaaaca 4020 aaagatctgc atccttagag accaagaagg atgtaaatga cactggcagt tttaagcctc 4080 cagaagtagc atctaaacct tcaggtgctc ccatcattgg tcccaaaccc acttctcaga 4140 atcaattcag tgaacatgac aaaactctgt acaggatccc agaacctcaa aaacctcaac 4200 tgaagccacc tgaagatatt gttcggtcca atcattatga ccctgaagaa gatgaagaat 4260 attatcgaaa acagctgtca tactttgacc gaagaagttt tgagaataag cctcctgcac 4320 acattgccgc cagccatctc tccgagcctg caaagccagc gcattctcag aatcaatcaa 4380 atttttctag ttattcttca aagggaaagc ctcctgaagc tgatggtgtg gatagatcat 4440 ttggcgagaa acgctatgaa cccatccagg ccactccccc tcctcctcca ttgccctcgc 4500 agtatgccca gccatctcag cctgtcacca gcgcgtctct ccacatacat tctaagggag 4560 cacatggtga aggtaattca gtgtcattgg attttcagaa ttccttagtg tccaaaccag 4620 acccacctcc atctcagaat aagccagcaa ctttcagacc accaaaccga gaagatactg 4680 ctcaggcagc tttctatccc cagaaaagtt ttccagataa agccccagtt aatggaactg 4740 aacagactca gaaaacagtc actccagcat acaatcgatt cacaccaaaa ccatatacaa 4800 gttctgcccg accatttgaa cgcaagtttg aaagtcctaa attcaatcac aatcttctgc 4860 caagtgaaac tgcacataaa cctgacttgt cttcaaaaac tcccacttct ccaaaaactc 4920 ttgtgaaatc gcacagtttg gcacagcctc ctgagtttga cagtggagtt gaaactttct 4980 ctatccatgc agagaagcct aaatatcaaa taaataatat cagcacagtg cctaaagcta 5040 ttcctgtgag tccttcagct gtggaagagg atgaagatga agatggtcat actgtggtgg 5100 ccacagcccg aggcatattt aacagcaatg ggggcgtgct gagttccata gaaactggtg 5160 ttagtataat tatccctcaa ggagccattc ccgaaggagt tgagcaggaa atctatttca 5220 aggtctgccg ggacaacagc atccttccac ctttagataa agagaaaggt gaaacactgc 5280 tgagtccttt ggtgatgtgt ggtccccatg gcctcaagtt cctgaagcct gtggagctgc 5340 gcttaccaca ctgtgatcct aaaacctggc aaaacaagtg tcttcccgga gatccaaatt 5400 atctcgttgg agcaaactgt gtttctgtcc ttattgacca cttttaactc ttgaaatata 5460 ggaacttaaa taatgtgaaa ctggattaaa cttaatctaa atggaaccac tctatcaagt 5520 attatacctt ttttagagtt gatactacag tttgttagta tgaggcattt gtttgaactg 5580 ataaagatga gtgagcatgc ccctgaacca tggtcggaaa acatgctaca cactgcatgt 5640 ttgtgattga cgggactgtt ggtattggct agaggttcaa agatattttg ctttgtgatt 5700 tttgtaattt ttttatcgtc actgcttaac ttcacatatt gatttccgtt aaaataccag 5760 ccagtaaatg ggggtgcatt tgaggtctgt tctttccaaa gtacactgtt tcaaacttta 5820 ctatggccct ggcctagcat acgtacacat tttattttat tatgcatgaa gtaatatgca 5880 cacatttttt aaatgcacct ggaatatata accagtgttg tggatttaac agaaatgtac 5940 agcaaggaga tttacaactg ggggagggtg aagtgaagac aatgacttac tgtacatgaa 6000 aacacatttt tcttagggaa ggatacaaaa gcatgtgaga ctggttccat ggcctcttca 6060 gatctctaac ttcaccatat taccacagac atactaacca gcagaaatgc cttaccctca 6120 tgttcttaat tcttagctca ttctccttgt gttactaagt ttttatggct tttgtgcatt 6180 atctagatac tgtatcatga caaagactga gtacgttgtg catttggtgg tttcagaaat 6240 gtgttatcac ccagaagaaa atagtggtgt gatttgggga tatttttttc ttttcttttc 6300 ttttcttttt tttttttttt gacaaggggc agtggtggtt ttctgttctt tctggctatg 6360 catttgaaaa ttttgatgtt ttaaggatgc ttgtacataa tgcgtgcata ccacttttgt 6420 tcttggtttg taaattaact tttataaact ttaccttttt tatacataaa caagaccacg 6480 tttctaaagg ctacctttgt attctctcct gtacctcttg agccttgaac tttgacctct 6540 gcagcaataa agcagcgttt ctatgacaca tgcaaggtca ttttttttaa gaaaaaggat 6600 gcacagagtt gttacatttt taagtgctgc atttaaaaga tacagttact cagaattctc 6660 tagtttgatt aaattcttgc aaagtatccc tactgtaatt tgtgatacaa tgctgtgccc 6720 taaagtgtat ttttttacta atagacaatt tattatggca catcagcacg atttctgttt 6780 agataataca ccactacatt ctgttaatca ttaggtgtga ctgaatttct tttgccgtta 6840 ttaaaaatct caaatttcta aatctccaaa ataaaacttt ttaaaataaa gtgctggctt 6900 ggtctgtttg cccactgttt tctagtttca tgcagcttta taatcctgtt ttaaaatcct 6960 gcacacaaat ccctatcacc cagcgtcacc taccacctcg tcgtctggtg ttgcatgcag 7020 aatttctccc cttggccagc atgtacagat gggtgggcag tgctcatctg aagggctcag 7080 actgaagtgg ggcagaagga cctggagaca gagtgggaga aggcagcagg ccgacttccc 7140 cctgtgggta aacacacacc cctgcgtgga gaaacacccc tgcatgggga cacacgtgcg 7200 tttgtgtgtg tgcgtgtaac catttgtata tggttttatt ccccagataa atagcacggg 7260 cattgtttaa tgtcacccac atttggggga agaaaatggg tttagtgagc ataaatattc 7320 cattgtggac atcctactta cttaactgcc acccctgttg acatttggat tattgctata 7380 gtgtttcagt aaacaccttt gtggactgaa tccatctatg tggattttat ttttttcatc 7440 tttgttaagg tataatttac atagagtaag ttactgtttt taaaatgtat agttcaaatt 7500 ttgacaaaca catactgttt atttaccacg gttaatacat acaacagttt ctttatcttc 7560 tctaatcatt tgtacccctt tatactcaac ccttcttcca gcccctggca ggatgatctc 7620 ttctgtttct atagttgcct ttttgacagt gtcatataaa tggaatcata caata 7675 <![CDATA[<210> 120]]> <![CDATA[<211> 5789]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 120]]> actcattctc cgatcagcgc gtgaacgcag ctcggctgcc gctggcagga aacaattctg 60 caaaaataat catactcagc ctggcaattg tctgccccta ggtctgtcgc tcagccgccg 120 tccacactcg ctgcaggggg gggggcacag aatttaccgc ggcaagaaca tccctcccag 180 ccagcagatt acaatgctgc aaactaagga tctcatctgg actttgtttt tcctgggaac 240 tgcagtttct ctgcaggtgg atattgttcc cagccagggg gagatcagcg ttggagagtc 300 caaattcttc ttatgccaag tggcaggaga tgccaaagat aaagacatct cctggttctc 360 ccccaatgga gaaaagctca ccccaaacca gcagcggatc tcagtggtgt ggaatgatga 420 ttcctcctcc accctcacca tctataacgc caacatcgac gacgccggca tttacaagtg 480 tgtggttaca ggcgaggatg gcagtgagtc agaggccacc gtcaacgtga agatctttca 540 gaagctcatg ttcaagaatg cgccaacccc acaggagttc cgggaggggg aagatgccgt 600 gattgtgtgt gatgtggtca gctccctccc accaaccatc atctggaaac acaaaggccg 660 agatgtcatc ctgaaaaaag atgtccgatt catagtcctg tccaacaact acctgcagat 720 ccggggcatc aagaaaacag atgagggcac ttatcgctgt gagggcagaa tcctggcacg 780 gggggagatc aacttcaagg acattcaggt cattgtgaat gtgccaccta ccatccaggc 840 caggcagaat attgtgaatg ccaccgccaa cctcggccag tccgtcaccc tggtgtgcga 900 tgccgaaggc ttcccagagc ccaccatgag ctggacaaag gatggggaac agatagagca 960 agaggaagac gatgagaagt acatcttcag cgacgatagt tcccagctga ccatcaaaaa 1020 ggtggataag aacgacgagg ctgagtacat ctgcattgct gagaacaagg ctggcgagca 1080 ggatgcgacc atccacctca aagtctttgc aaaacccaaa atcacatatg tagagaacca 1140 gactgccatg gaattagagg agcaggtcac tcttacctgt gaagcctccg gagaccccat 1200 tccctccatc acctggagga cttctacccg gaacatcagc agcgaagaaa agactctgga 1260 tgggcacatg gtggtgcgta gccatgcccg tgtgtcgtcg ctgaccctga agagcatcca 1320 gtacactgat gccggagagt acatctgcac cgccagcaac accatcggcc aggactccca 1380 gtccatgtac cttgaagtgc aatatgcccc aaagctacag ggccctgtgg ctgtgtacac 1440 ttgggagggg aaccaggtga acatcacctg cgaggtattt gcctatccca gtgccacgat 1500 ctcatggttt cgggatggcc agctgctgcc aagctccaat tacagcaata tcaagatcta 1560 caacaccccc tctgccagct atctggaggt gaccccagac tctgagaatg attttgggaa 1620 ctacaactgt actgcagtga accgcattgg gcaggagtcc ttggaattca tccttgttca 1680 agcagacacc ccctcttcac catccatcga ccaggtggag ccatactcca gcacagccca 1740 ggtgcagttt gatgaaccag aggccacagg tggggtgccc atcctcaaat acaaagctga 1800 gtggagagca gttggtgaag aagtatggca ttccaagtgg tatgatgcca aggaagccag 1860 catggagggc atcgtcacca tcgtgggcct gaagcccgaa acaacgtacg ccgtaaggct 1920 ggcggcgctc aatggcaaag ggctgggtga gatcagcgcg gcctccgagt tcaagacgca 1980 gccagtccaa ggggaaccca gtgcacctaa gctcgaaggg cagatgggag aggatggaaa 2040 ctctattaaa gtgaacctga tcaagcagga tgacggcggc tcccccatca gacactatct 2100 ggtcaggtac cgagcgctct cctccgagtg gaaaccagag atcaggctcc cgtctggcag 2160 tgaccacgtc atgctgaagt ccctggactg gaatgctgag tatgaggtct acgtggtggc 2220 tgagaaccag caaggaaaat ccaaggcggc tcattttgtg ttcaggacct cggcccagcc 2280 cacagccatc ccagccaacg gcagccccac ctcaggcctg agcaccgggg ccatcgtggg 2340 catcctcatc gtcatcttcg tcctgctcct ggtggttgtg gacatcacct gctacttcct 2400 gaacaagtgt ggcctgttca tgtgcattgc ggtcaacctg tgtggaaaag ccgggcccgg 2460 ggccaagggc aaggacatgg aggagggcaa ggccgccttc tcgaaagatg agtccaagga 2520 gcccatcgtg gaggttcgaa cggaggagga gaggacccca aaccatgatg gagggaaaca 2580 cacagagccc aacgagacca cgccactgac ggagcccgag aagggccccg tagaagcaaa 2640 gccagagtgc caggagacag aaacgaagcc agcgccagcc gaagtcaaga cggtccccaa 2700 tgacgccaca cagacaaagg agaacgagag caaagcatga tgggtgaaga gaaccgagca 2760 aagatcaaaa taaaaagtga cacagcagct tcaccagagc atttccaaca ccacagacac 2820 acacacgcac gcacacacac aaacacacat gcacacacac acatctcatt tctctagtgt 2880 cttttgcctt taaaaaaaac taaacagata aaacatggga atctcctttt tgtaggttta 2940 tagaaagggt ccctttgttg cacactcact tgtaagaaaa tgagacaaaa aggttaaacc 3000 cacagccaaa ctaggacact ccgttccctg aaaccgttaa aaaatcaaac aaaaggaccc 3060 caaattaaga atctaggaag ctcagaaacg aaatctaggt tcaggaagac cacacttggt 3120 gttacccgat tggcacagac cagtttcaga gaaatacttt caggcactaa gactaatcga 3180 atgaacaaag tccacagttt atttttatac tttcagtcaa gtttgaactc tgtaaaacct 3240 cataaataag ttataatttc tgttcacttt gtatttgttc agtatgcaaa gtgtgtcacc 3300 ctttctagct gaattcaatt cccacgtaga ctcttatttt ataggacgaa tgccaaattg 3360 cagcttctgg gggtagatct caatttgcag tattcagact tctttttctt tcttttacat 3420 tcttttttct ttctttcttt ctgccaactt tgttttccag tgtttacaag gtgacaaatg 3480 tttgactttg gttgtgttta aatgtccgtg taaaatagct gccttttatt ttttaaggta 3540 acaaatacca cctagaggta ggtaggatca tcccacgctt gctttagcac aggacaactt 3600 tacaaaacat gattgtttac agctgctctt cccctctttt ctgatctgca gtttttgcct 3660 gggtcccact caggtgaaaa tccatctcat tctggaatgg ttttgctttt gaatttttgg 3720 ttatttttgt gtttctttgg gggttagacc actttctgat tagccgccac ctgcctgcat 3780 ctgtgaaaag ggatctgctc ccaggcgttc tcacccttct tttgaaggac tccttaggct 3840 ttgttgaatg aagcagagaa gattgtatag ttggggctgg tcttggtgaa cacacattat 3900 taccccacac atcccctttg tgtagaaagc caaataaaat ctatacatac catttccttt 3960 tgagcccaga atctagattt gagcggaaga gcatgtgtgc ttcagggaat tagtgtcttt 4020 ttttggaaat ctgttgaagt aaagtaacat cggccttctg ttcacttagg cagcatttat 4080 agaaacaaaa gaagaaagaa acaacctact gtctggagtc ataacacaac tttcctggat 4140 tggaaaccaa gtgggggaaa aaatacagaa actttaaggg ggatgggagg ggggggagaa 4200 gggaaaagcc agccctttgt atagaaattt tgcttttttt tccctcattc tactttagaa 4260 ctgcaagctt gtgcactgtg gatgcgtgaa tattttagtg tgaaacgtgt ttttgtcata 4320 gtattgaaat aaaacttcaa catagtttgg ttgtggaagg tatagcagat agttcagaaa 4380 aaatattcag gaaacaaaaa tcactcaaac ggaatcgaag ccttttaaca aagaaaatga 4440 aatacagatg atgatgatga tgatgaagat gatgctaagt aaacagaaat cagtactccg 4500 catgcgctcc tctcctaagg tacaaagcag caagaggtta gggtggcaag gctgcctctg 4560 ggtccattct gtgggccact ctccccaacg ttctgacact tctgcagtct gatcagtggc 4620 gatgctagat tataatttca aactgtgaag aataatggtc ttgtcatttg ctcaatgtgg 4680 ggttatgttg cattttctca gctcctgggg atggaaatgg aggatcccag aacacacagc 4740 cctggcccct ttgattctag ggcctgcaca gatctctggt tcaaatgcac aggccctcag 4800 aatagaggaa catgaagaga gatcttagag cacacagtag aatgtgagag cctgggtgtc 4860 tgagaccggg agggcccagc agtgaggggc aggctcttct ggtcaccagg ctgttcagtg 4920 gactcagttc ttcatcttgt aatgtcgatg gctttgccac accaggccaa gcccatgcca 4980 taccttgtca agactgtcaa agtggttgtg gttaggtcaa actggttttg gttctgatgg 5040 ttaggaagaa acaggtcagc cctcagatca cctggcccgg gacagctgac cccctagaac 5100 cctggctctg ccattagcta ggacctaaga ctctgcccac attttggtct gttctctccc 5160 attacacata ggtttgtctc agcatgcaag agtttttcct ttaaaaaaaa aaaaaaaaaa 5220 aaaaaaaaag caatgctttc tctaaaatca aagagggagt cattttattc caagatgttt 5280 tatcttttat gttaagagat caaagcttat aattttcttt tttaattttt gaaggaggga 5340 tcaactccag tttccaatgt ctatgtgtct atgtgtgtat gtgccataca tatgtattca 5400 catgaagacc ggcatggcca agttctgctg gaggagcact caagtgtgac gagcagggcc 5460 actggaccct gcagggctgt ggtgtatata gtgcagcttt ggaggtggaa ctctattttc 5520 acacttttct atggagcctt ccgagtccca ggttttcact tgaggctgtc tgtctggatg 5580 gcggttttca gacctccatt aacatcccta cccagcattc tgtacttcgg gggccttctc 5640 tcttgttata aaacttttta ccaagtgaaa catcgatacc acctttgttt ccattctcac 5700 tggtgtaaat actgagtact aactgagaat tttgactttg cattctgtcg gaatacttgt 5760 gttcaataaa aattgaaaga aaaaagcta 5789 <![CDATA[<210> 121]]> <![CDATA[<211> 4751]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 121]]> actcattctc cgatcagcgc gtgaacgcag ctcggctgcc gctggcagga aacaattctg 60 caaaaataat catactcagc ctggcaattg tctgccccta ggtctgtcgc tcagccgccg 120 tccacactcg ctgcaggggg gggggcacag aatttaccgc ggcaagaaca tccctcccag 180 ccagcagatt acaatgctgc aaactaagga tctcatctgg actttgtttt tcctgggaac 240 tgcagtttct ctgcaggtgg atattgttcc cagccagggg gagatcagcg ttggagagtc 300 caaattcttc ttatgccaag tggcaggaga tgccaaagat aaagacatct cctggttctc 360 ccccaatgga gaaaagctca ccccaaacca gcagcggatc tcagtggtgt ggaatgatga 420 ttcctcctcc accctcacca tctataacgc caacatcgac gacgccggca tttacaagtg 480 tgtggttaca ggcgaggatg gcagtgagtc agaggccacc gtcaacgtga agatctttca 540 gaagctcatg ttcaagaatg cgccaacccc acaggagttc cgggaggggg aagatgccgt 600 gattgtgtgt gatgtggtca gctccctccc accaaccatc atctggaaac acaaaggccg 660 agatgtcatc ctgaaaaaag atgtccgatt catagtcctg tccaacaact acctgcagat 720 ccggggcatc aagaaaacag atgagggcac ttatcgctgt gagggcagaa tcctggcacg 780 gggggagatc aacttcaagg acattcaggt cattgtgaat gtgccaccta ccatccaggc 840 caggcagaat attgtgaatg ccaccgccaa cctcggccag tccgtcaccc tggtgtgcga 900 tgccgaaggc ttcccagagc ccaccatgag ctggacaaag gatggggaac agatagagca 960 agaggaagac gatgagaagt acatcttcag cgacgatagt tcccagctga ccatcaaaaa 1020 ggtggataag aacgacgagg ctgagtacat ctgcattgct gagaacaagg ctggcgagca 1080 ggatgcgacc atccacctca aagtctttgc aaaacccaaa atcacatatg tagagaacca 1140 gactgccatg gaattagagg agcaggtcac tcttacctgt gaagcctccg gagaccccat 1200 tccctccatc acctggagga cttctacccg gaacatcagc agcgaagaaa agactctgga 1260 tgggcacatg gtggtgcgta gccatgcccg tgtgtcgtcg ctgaccctga agagcatcca 1320 gtacactgat gccggagagt acatctgcac cgccagcaac accatcggcc aggactccca 1380 gtccatgtac cttgaagtgc aatatgcccc aaagctacag ggccctgtgg ctgtgtacac 1440 ttgggagggg aaccaggtga acatcacctg cgaggtattt gcctatccca gtgccacgat 1500 ctcatggttt cgggatggcc agctgctgcc aagctccaat tacagcaata tcaagatcta 1560 caacaccccc tctgccagct atctggaggt gaccccagac tctgagaatg attttgggaa 1620 ctacaactgt actgcagtga accgcattgg gcaggagtcc ttggaattca tccttgttca 1680 agcagacacc ccctcttcac catccatcga ccaggtggag ccatactcca gcacagccca 1740 ggtgcagttt gatgaaccag aggccacagg tggggtgccc atcctcaaat acaaagctga 1800 gtggagagca gttggtgaag aagtatggca ttccaagtgg tatgatgcca aggaagccag 1860 catggagggc atcgtcacca tcgtgggcct gaagcccgaa acaacgtacg ccgtaaggct 1920 ggcggcgctc aatggcaaag ggctgggtga gatcagcgcg gcctccgagt tcaagacgca 1980 gccagtccat agccctcctc caccggcatc tgctagctcg tctacccctg ttccattgtc 2040 tccaccagat acaacttggc ctcttcctgc ccttgcaacc acagaaccag ctaaagggga 2100 acccagtgca cctaagctcg aagggcagat gggagaggat ggaaactcta ttaaagtgaa 2160 cctgatcaag caggatgacg gcggctcccc catcagacac tatctggtca ggtaccgagc 2220 gctctcctcc gagtggaaac cagagatcag gctcccgtct ggcagtgacc acgtcatgct 2280 gaagtccctg gactggaatg ctgagtatga ggtctacgtg gtggctgaga accagcaagg 2340 aaaatccaag gcggctcatt ttgtgttcag gacctcggcc cagcccacag ccatcccagc 2400 aaccttggga ggcaattctg catcctacac ctttgtctca ttgcttttct ctgcagtgac 2460 tcttcttttg ctctgttagg aacttgaaca caaaaattaa atttgcttaa aagcccagtt 2520 cctatgaaaa agatcagtgc cccctttgga agaacctggc aggaccacca tggccacagc 2580 tgctgagcaa ccattctgtg tggaagagaa ggttttgtga ttggaaaaag ctttacctcc 2640 agacatgtca ccactcacag atacttttgt gccacttcat aaggagtttg cccccttttt 2700 aatggcagta aaaagaattt gagagctctt tctttaaatg ctatttttaa aaaccatcat 2760 gctagattta cagagaagtt tctgcatatc tgctacttgt tgcattttgg gttcaaacct 2820 aaatatgatg tagcagagga agaattctaa gtaccttcta aagcttgtgt cagattgtta 2880 aaatcaccac acattcccct cattctaact ctgtgctcct tgtcctccct tcaataataa 2940 ttggctttgc ttgcaattaa gcatttaagt gcccatgtta aaagagccag accgcactga 3000 ttcacatgag cgttttgctg acatgatggg caactgaagt cacccctgtt gcccatgcac 3060 tggaaaaaaa gttgaatttg ttggatattt tctggggctg atgaacgttc tgggatgtgc 3120 tttcagtcct cgtattacgg ccagcacctt acactgtctc tgtgaacggg gccaagccat 3180 gatgtgccaa caagtgtcag ctttgaaagg tgtttgtctc ccaatcgggg tgactcccct 3240 gctgcctggc agcatgtcgc agatcagcac agagtggggc cgtggttcag cagtgaccca 3300 cagaatggct ttgagcatca gtctacagga caggttggaa gcatccactg tgaaccaggc 3360 attagtcccc tacctggcct gtgtgtgctc agtagagaag gagagggaca ggccactccc 3420 agactgccca gcccaggagg gttaataaat tggggccgag ccaacctgtc agtgcttcct 3480 gaatgcccca gcctctgtat tggtgcgttg gttcagtgac attttctaaa ctctcctgaa 3540 aatccagctg ctcctccctg ctgcttggga gttcacccag gagaggaaat gggtgtgttt 3600 tgttaaggtc ccttgtggag actcagggct gaatcctgct tggtaatatc agtgtgtgtg 3660 cttggggatg gaccttctac tgaataaaaa ctccctccct ccccccattg tggtcacata 3720 tcattctaca tatctcatct ctgagcatct ccatggaagc ttgatttttg ttctttttgg 3780 tttctttatg tatttttttc tgttgttatt attttttaat gttcaaagac tagcctttcc 3840 ctttgggatt ccaaatgatc ccatgctgtg gtctgagggg caaagccacc tatgttggcg 3900 ctcgccatta atccccagcg ctcagtttag aggctcacgt gcagacatca gaggctccat 3960 gctgcacagt agctcaggca gggtagtgcc tctcaaccca gccacaaaac tctccccgct 4020 ggagtcccag atggcgcttc acaccagggc agtggaggca ggcatggttt ttgggcacag 4080 ggcagagcat aaggatccca ggtcagtgtg ggagagctac tggctcttag gatcaccttg 4140 ggcagaagtc acacggcttc atcctaggag ggcccagctt gggagtctgc ctccccctga 4200 tcccaggacc acccacagga gaggggcagt gtccatcttt ctgaagggac cctttggaga 4260 tctcgtccta agtgtggaga ggactgacgt ggccctgtca tctcaacaca tcccagggtc 4320 aggcaggcct cagctgaaac aatgtcaggg tcctcaaggg tcccatttag acagacccac 4380 ggcttgtaac agtgcgctcc tcaggaggca gcactagcgc atacccactc cccacggaca 4440 ctgagttcct ggtgacagct gcagccccag ccccgccagg agtcctggag acagcagccc 4500 tcagagaccc tgcaggagtg agtgcacccc accttgctca gccacacccc actcccctgt 4560 gccctgtagt tgtgctgccc atgctccaca caccatgggg cccctttgct catttttgga 4620 ctatttatac agcaggtttg gatcatgttt ttctactaat aagaatgcta acattgttgt 4680 gtagataatc agtgagggct ttatgaagtt tacacctttg cattattaaa ggaaataaca 4740 gttcatgtga a 4751 <![CDATA[<210> 122]]> <![CDATA[<211> 5897]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 122]]> actcattctc cgatcagcgc gtgaacgcag ctcggctgcc gctggcagga aacaattctg 60 caaaaataat catactcagc ctggcaattg tctgccccta ggtctgtcgc tcagccgccg 120 tccacactcg ctgcaggggg gggggcacag aatttaccgc ggcaagaaca tccctcccag 180 ccagcagatt acaatgctgc aaactaagga tctcatctgg actttgtttt tcctgggaac 240 tgcagtttct ctgcaggtgg atattgttcc cagccagggg gagatcagcg ttggagagtc 300 caaattcttc ttatgccaag tggcaggaga tgccaaagat aaagacatct cctggttctc 360 ccccaatgga gaaaagctca ccccaaacca gcagcggatc tcagtggtgt ggaatgatga 420 ttcctcctcc accctcacca tctataacgc caacatcgac gacgccggca tttacaagtg 480 tgtggttaca ggcgaggatg gcagtgagtc agaggccacc gtcaacgtga agatctttca 540 gaagctcatg ttcaagaatg cgccaacccc acaggagttc cgggaggggg aagatgccgt 600 gattgtgtgt gatgtggtca gctccctccc accaaccatc atctggaaac acaaaggccg 660 agatgtcatc ctgaaaaaag atgtccgatt catagtcctg tccaacaact acctgcagat 720 ccggggcatc aagaaaacag atgagggcac ttatcgctgt gagggcagaa tcctggcacg 780 gggggagatc aacttcaagg acattcaggt cattgtgaat gtgccaccta ccatccaggc 840 caggcagaat attgtgaatg ccaccgccaa cctcggccag tccgtcaccc tggtgtgcga 900 tgccgaaggc ttcccagagc ccaccatgag ctggacaaag gatggggaac agatagagca 960 agaggaagac gatgagaagt acatcttcag cgacgatagt tcccagctga ccatcaaaaa 1020 ggtggataag aacgacgagg ctgagtacat ctgcattgct gagaacaagg ctggcgagca 1080 ggatgcgacc atccacctca aagtctttgc aaaacccaaa atcacatatg tagagaacca 1140 gactgccatg gaattagagg agcaggtcac tcttacctgt gaagcctccg gagaccccat 1200 tccctccatc acctggagga cttctacccg gaacatcagc agcgaagaaa aggcttcgtg 1260 gactcgacca gagaagcaag aggtacatgc accatggaac tggcaagtgg gcagacagaa 1320 aggacaggct ggcagtgcag gtttcccagg atctcatgag actctggatg ggcacatggt 1380 ggtgcgtagc catgcccgtg tgtcgtcgct gaccctgaag agcatccagt acactgatgc 1440 cggagagtac atctgcaccg ccagcaacac catcggccag gactcccagt ccatgtacct 1500 tgaagtgcaa tatgccccaa agctacaggg ccctgtggct gtgtacactt gggaggggaa 1560 ccaggtgaac atcacctgcg aggtatttgc ctatcccagt gccacgatct catggtttcg 1620 ggatggccag ctgctgccaa gctccaatta cagcaatatc aagatctaca acaccccctc 1680 tgccagctat ctggaggtga ccccagactc tgagaatgat tttgggaact acaactgtac 1740 tgcagtgaac cgcattgggc aggagtcctt ggaattcatc cttgttcaag cagacacccc 1800 ctcttcacca tccatcgacc aggtggagcc atactccagc acagcccagg tgcagtttga 1860 tgaaccagag gccacaggtg gggtgcccat cctcaaatac aaagctgagt ggagagcagt 1920 tggtgaagaa gtatggcatt ccaagtggta tgatgccaag gaagccagca tggagggcat 1980 cgtcaccatc gtgggcctga agcccgaaac aacgtacgcc gtaaggctgg cggcgctcaa 2040 tggcaaaggg ctgggtgaga tcagcgcggc ctccgagttc aagacgcagc cagtccaagg 2100 ggaacccagt gcacctaagc tcgaagggca gatgggagag gatggaaact ctattaaagt 2160 gaacctgatc aagcaggatg acggcggctc ccccatcaga cactatctgg tcaggtaccg 2220 agcgctctcc tccgagtgga aaccagagat caggctcccg tctggcagtg accacgtcat 2280 gctgaagtcc ctggactgga atgctgagta tgaggtctac gtggtggctg agaaccagca 2340 aggaaaatcc aaggcggctc attttgtgtt caggacctcg gcccagccca cagccatccc 2400 agccaacggc agccccacct caggcctgag caccggggcc atcgtgggca tcctcatcgt 2460 catcttcgtc ctgctcctgg tggttgtgga catcacctgc tacttcctga acaagtgtgg 2520 cctgttcatg tgcattgcgg tcaacctgtg tggaaaagcc gggcccgggg ccaagggcaa 2580 ggacatggag gagggcaagg ccgccttctc gaaagatgag tccaaggagc ccatcgtgga 2640 ggttcgaacg gaggaggaga ggaccccaaa ccatgatgga gggaaacaca cagagcccaa 2700 cgagaccacg ccactgacgg agcccgagaa gggccccgta gaagcaaagc cagagtgcca 2760 ggagacagaa acgaagccag cgccagccga agtcaagacg gtccccaatg acgccacaca 2820 gacaaaggag aacgagagca aagcatgatg ggtgaagaga accgagcaaa gatcaaaata 2880 aaaagtgaca cagcagcttc accagagcat ttccaacacc acagacacac acacgcacgc 2940 acacacacaa acacacatgc acacacacac atctcatttc tctagtgtct tttgccttta 3000 aaaaaaacta aacagataaa acatgggaat ctcctttttg taggtttata gaaagggtcc 3060 ctttgttgca cactcacttg taagaaaatg agacaaaaag gttaaaccca cagccaaact 3120 aggacactcc gttccctgaa accgttaaaa aatcaaacaa aaggacccca aattaagaat 3180 ctaggaagct cagaaacgaa atctaggttc aggaagacca cacttggtgt tacccgattg 3240 gcacagacca gtttcagaga aatactttca ggcactaaga ctaatcgaat gaacaaagtc 3300 cacagtttat ttttatactt tcagtcaagt ttgaactctg taaaacctca taaataagtt 3360 ataatttctg ttcactttgt atttgttcag tatgcaaagt gtgtcaccct ttctagctga 3420 attcaattcc cacgtagact cttattttat aggacgaatg ccaaattgca gcttctgggg 3480 gtagatctca atttgcagta ttcagacttc tttttctttc ttttacattc ttttttcttt 3540 ctttctttct gccaactttg ttttccagtg tttacaaggt gacaaatgtt tgactttggt 3600 tgtgtttaaa tgtccgtgta aaatagctgc cttttatttt ttaaggtaac aaataccacc 3660 tagaggtagg taggatcatc ccacgcttgc tttagcacag gacaacttta caaaacatga 3720 ttgtttacag ctgctcttcc cctcttttct gatctgcagt ttttgcctgg gtcccactca 3780 ggtgaaaatc catctcattc tggaatggtt ttgcttttga atttttggtt atttttgtgt 3840 ttctttgggg gttagaccac tttctgatta gccgccacct gcctgcatct gtgaaaaggg 3900 atctgctccc aggcgttctc acccttcttt tgaaggactc cttaggcttt gttgaatgaa 3960 gcagagaaga ttgtatagtt ggggctggtc ttggtgaaca cacattatta ccccacacat 4020 cccctttgtg tagaaagcca aataaaatct atacatacca tttccttttg agcccagaat 4080 ctagatttga gcggaagagc atgtgtgctt cagggaatta gtgtcttttt ttggaaatct 4140 gttgaagtaa agtaacatcg gccttctgtt cacttaggca gcatttatag aaacaaaaga 4200 agaaagaaac aacctactgt ctggagtcat aacacaactt tcctggattg gaaaccaagt 4260 gggggaaaaa atacagaaac tttaaggggg atgggagggg ggggagaagg gaaaagccag 4320 ccctttgtat agaaattttg cttttttttc cctcattcta ctttagaact gcaagcttgt 4380 gcactgtgga tgcgtgaata ttttagtgtg aaacgtgttt ttgtcatagt attgaaataa 4440 aacttcaaca tagtttggtt gtggaaggta tagcagatag ttcagaaaaa atattcagga 4500 aacaaaaatc actcaaacgg aatcgaagcc ttttaacaaa gaaaatgaaa tacagatgat 4560 gatgatgatg atgaagatga tgctaagtaa acagaaatca gtactccgca tgcgctcctc 4620 tcctaaggta caaagcagca agaggttagg gtggcaaggc tgcctctggg tccattctgt 4680 gggccactct ccccaacgtt ctgacacttc tgcagtctga tcagtggcga tgctagatta 4740 taatttcaaa ctgtgaagaa taatggtctt gtcatttgct caatgtgggg ttatgttgca 4800 ttttctcagc tcctggggat ggaaatggag gatcccagaa cacacagccc tggccccttt 4860 gattctaggg cctgcacaga tctctggttc aaatgcacag gccctcagaa tagaggaaca 4920 tgaagagaga tcttagagca cacagtagaa tgtgagagcc tgggtgtctg agaccgggag 4980 ggcccagcag tgaggggcag gctcttctgg tcaccaggct gttcagtgga ctcagttctt 5040 catcttgtaa tgtcgatggc tttgccacac caggccaagc ccatgccata ccttgtcaag 5100 actgtcaaag tggttgtggt taggtcaaac tggttttggt tctgatggtt aggaagaaac 5160 aggtcagccc tcagatcacc tggcccggga cagctgaccc cctagaaccc tggctctgcc 5220 attagctagg acctaagact ctgcccacat tttggtctgt tctctcccat tacacatagg 5280 tttgtctcag catgcaagag tttttccttt aaaaaaaaaa aaaaaaaaaa aaaaaaagca 5340 atgctttctc taaaatcaaa gagggagtca ttttattcca agatgtttta tcttttatgt 5400 taagagatca aagcttataa ttttcttttt taatttttga aggagggatc aactccagtt 5460 tccaatgtct atgtgtctat gtgtgtatgt gccatacata tgtattcaca tgaagaccgg 5520 catggccaag ttctgctgga ggagcactca agtgtgacga gcagggccac tggaccctgc 5580 agggctgtgg tgtatatagt gcagctttgg aggtggaact ctattttcac acttttctat 5640 ggagccttcc gagtcccagg ttttcacttg aggctgtctg tctggatggc ggttttcaga 5700 cctccattaa catccctacc cagcattctg tacttcgggg gccttctctc ttgttataaa 5760 actttttacc aagtgaaaca tcgataccac ctttgtttcc attctcactg gtgtaaatac 5820 tgagtactaa ctgagaattt tgactttgca ttctgtcgga atacttgtgt tcaataaaaa 5880 ttgaaagaaa aaagcta 5897 <![CDATA[<210> 123]]> <![CDATA[<211> 4646]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 123]]> actcattctc cgatcagcgc gtgaacgcag ctcggctgcc gctggcagga aacaattctg 60 caaaaataat catactcagc ctggcaattg tctgccccta ggtctgtcgc tcagccgccg 120 tccacactcg ctgcaggggg gggggcacag aatttaccgc ggcaagaaca tccctcccag 180 ccagcagatt acaatgctgc aaactaagga tctcatctgg actttgtttt tcctgggaac 240 tgcagtttct ctgcaggtgg atattgttcc cagccagggg gagatcagcg ttggagagtc 300 caaattcttc ttatgccaag tggcaggaga tgccaaagat aaagacatct cctggttctc 360 ccccaatgga gaaaagctca ccccaaacca gcagcggatc tcagtggtgt ggaatgatga 420 ttcctcctcc accctcacca tctataacgc caacatcgac gacgccggca tttacaagtg 480 tgtggttaca ggcgaggatg gcagtgagtc agaggccacc gtcaacgtga agatctttca 540 gaagctcatg ttcaagaatg cgccaacccc acaggagttc cgggaggggg aagatgccgt 600 gattgtgtgt gatgtggtca gctccctccc accaaccatc atctggaaac acaaaggccg 660 agatgtcatc ctgaaaaaag atgtccgatt catagtcctg tccaacaact acctgcagat 720 ccggggcatc aagaaaacag atgagggcac ttatcgctgt gagggcagaa tcctggcacg 780 gggggagatc aacttcaagg acattcaggt cattgtgaat gtgccaccta ccatccaggc 840 caggcagaat attgtgaatg ccaccgccaa cctcggccag tccgtcaccc tggtgtgcga 900 tgccgaaggc ttcccagagc ccaccatgag ctggacaaag gatggggaac agatagagca 960 agaggaagac gatgagaagt acatcttcag cgacgatagt tcccagctga ccatcaaaaa 1020 ggtggataag aacgacgagg ctgagtacat ctgcattgct gagaacaagg ctggcgagca 1080 ggatgcgacc atccacctca aagtctttgc aaaacccaaa atcacatatg tagagaacca 1140 gactgccatg gaattagagg agcaggtcac tcttacctgt gaagcctccg gagaccccat 1200 tccctccatc acctggagga cttctacccg gaacatcagc agcgaagaaa agactctgga 1260 tgggcacatg gtggtgcgta gccatgcccg tgtgtcgtcg ctgaccctga agagcatcca 1320 gtacactgat gccggagagt acatctgcac cgccagcaac accatcggcc aggactccca 1380 gtccatgtac cttgaagtgc aatatgcccc aaagctacag ggccctgtgg ctgtgtacac 1440 ttgggagggg aaccaggtga acatcacctg cgaggtattt gcctatccca gtgccacgat 1500 ctcatggttt cgggatggcc agctgctgcc aagctccaat tacagcaata tcaagatcta 1560 caacaccccc tctgccagct atctggaggt gaccccagac tctgagaatg attttgggaa 1620 ctacaactgt actgcagtga accgcattgg gcaggagtcc ttggaattca tccttgttca 1680 agcagacacc ccctcttcac catccatcga ccaggtggag ccatactcca gcacagccca 1740 ggtgcagttt gatgaaccag aggccacagg tggggtgccc atcctcaaat acaaagctga 1800 gtggagagca gttggtgaag aagtatggca ttccaagtgg tatgatgcca aggaagccag 1860 catggagggc atcgtcacca tcgtgggcct gaagcccgaa acaacgtacg ccgtaaggct 1920 ggcggcgctc aatggcaaag ggctgggtga gatcagcgcg gcctccgagt tcaagacgca 1980 gccagtccaa ggggaaccca gtgcacctaa gctcgaaggg cagatgggag aggatggaaa 2040 ctctattaaa gtgaacctga tcaagcagga tgacggcggc tcccccatca gacactatct 2100 ggtcaggtac cgagcgctct cctccgagtg gaaaccagag atcaggctcc cgtctggcag 2160 tgaccacgtc atgctgaagt ccctggactg gaatgctgag tatgaggtct acgtggtggc 2220 tgagaaccag caaggaaaat ccaaggcggc tcattttgtg ttcaggacct cggcccagcc 2280 cacagccatc ccagcaacct tgggaggcaa ttctgcatcc tacacctttg tctcattgct 2340 tttctctgca gtgactcttc ttttgctctg ttaggaactt gaacacaaaa attaaatttg 2400 cttaaaagcc cagttcctat gaaaaagatc agtgccccct ttggaagaac ctggcaggac 2460 caccatggcc acagctgctg agcaaccatt ctgtgtggaa gagaaggttt tgtgattgga 2520 aaaagcttta cctccagaca tgtcaccact cacagatact tttgtgccac ttcataagga 2580 gtttgccccc tttttaatgg cagtaaaaag aatttgagag ctctttcttt aaatgctatt 2640 tttaaaaacc atcatgctag atttacagag aagtttctgc atatctgcta cttgttgcat 2700 tttgggttca aacctaaata tgatgtagca gaggaagaat tctaagtacc ttctaaagct 2760 tgtgtcagat tgttaaaatc accacacatt cccctcattc taactctgtg ctccttgtcc 2820 tcccttcaat aataattggc tttgcttgca attaagcatt taagtgccca tgttaaaaga 2880 gccagaccgc actgattcac atgagcgttt tgctgacatg atgggcaact gaagtcaccc 2940 ctgttgccca tgcactggaa aaaaagttga atttgttgga tattttctgg ggctgatgaa 3000 cgttctggga tgtgctttca gtcctcgtat tacggccagc accttacact gtctctgtga 3060 acggggccaa gccatgatgt gccaacaagt gtcagctttg aaaggtgttt gtctcccaat 3120 cggggtgact cccctgctgc ctggcagcat gtcgcagatc agcacagagt ggggccgtgg 3180 ttcagcagtg acccacagaa tggctttgag catcagtcta caggacaggt tggaagcatc 3240 cactgtgaac caggcattag tcccctacct ggcctgtgtg tgctcagtag agaaggagag 3300 ggacaggcca ctcccagact gcccagccca ggagggttaa taaattgggg ccgagccaac 3360 ctgtcagtgc ttcctgaatg ccccagcctc tgtattggtg cgttggttca gtgacatttt 3420 ctaaactctc ctgaaaatcc agctgctcct ccctgctgct tgggagttca cccaggagag 3480 gaaatgggtg tgttttgtta aggtcccttg tggagactca gggctgaatc ctgcttggta 3540 atatcagtgt gtgtgcttgg ggatggacct tctactgaat aaaaactccc tccctccccc 3600 cattgtggtc acatatcatt ctacatatct catctctgag catctccatg gaagcttgat 3660 ttttgttctt tttggtttct ttatgtattt ttttctgttg ttattatttt ttaatgttca 3720 aagactagcc tttccctttg ggattccaaa tgatcccatg ctgtggtctg aggggcaaag 3780 ccacctatgt tggcgctcgc cattaatccc cagcgctcag tttagaggct cacgtgcaga 3840 catcagaggc tccatgctgc acagtagctc aggcagggta gtgcctctca acccagccac 3900 aaaactctcc ccgctggagt cccagatggc gcttcacacc agggcagtgg aggcaggcat 3960 ggtttttggg cacagggcag agcataagga tcccaggtca gtgtgggaga gctactggct 4020 cttaggatca ccttgggcag aagtcacacg gcttcatcct aggagggccc agcttgggag 4080 tctgcctccc cctgatccca ggaccaccca caggagaggg gcagtgtcca tctttctgaa 4140 gggacccttt ggagatctcg tcctaagtgt ggagaggact gacgtggccc tgtcatctca 4200 acacatccca gggtcaggca ggcctcagct gaaacaatgt cagggtcctc aagggtccca 4260 tttagacaga cccacggctt gtaacagtgc gctcctcagg aggcagcact agcgcatacc 4320 cactccccac ggacactgag ttcctggtga cagctgcagc cccagccccg ccaggagtcc 4380 tggagacagc agccctcaga gaccctgcag gagtgagtgc accccacctt gctcagccac 4440 accccactcc cctgtgccct gtagttgtgc tgcccatgct ccacacacca tggggcccct 4500 ttgctcattt ttggactatt tatacagcag gtttggatca tgtttttcta ctaataagaa 4560 tgctaacatt gttgtgtaga taatcagtga gggctttatg aagtttacac ctttgcatta 4620 ttaaaggaaa taacagttca tgtgaa 4646 <![CDATA[<210> 124]]> <![CDATA[<211> 4673]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 124]]> actcattctc cgatcagcgc gtgaacgcag ctcggctgcc gctggcagga aacaattctg 60 caaaaataat catactcagc ctggcaattg tctgccccta ggtctgtcgc tcagccgccg 120 tccacactcg ctgcaggggg gggggcacag aatttaccgc ggcaagaaca tccctcccag 180 ccagcagatt acaatgctgc aaactaagga tctcatctgg actttgtttt tcctgggaac 240 tgcagtttct ctgcaggtgg atattgttcc cagccagggg gagatcagcg ttggagagtc 300 caaattcttc ttatgccaag tggcaggaga tgccaaagat aaagacatct cctggttctc 360 ccccaatgga gaaaagctca ccccaaacca gcagcggatc tcagtggtgt ggaatgatga 420 ttcctcctcc accctcacca tctataacgc caacatcgac gacgccggca tttacaagtg 480 tgtggttaca ggcgaggatg gcagtgagtc agaggccacc gtcaacgtga agatctttca 540 gaagctcatg ttcaagaatg cgccaacccc acaggagttc cgggaggggg aagatgccgt 600 gattgtgtgt gatgtggtca gctccctccc accaaccatc atctggaaac acaaaggccg 660 agatgtcatc ctgaaaaaag atgtccgatt catagtcctg tccaacaact acctgcagat 720 ccggggcatc aagaaaacag atgagggcac ttatcgctgt gagggcagaa tcctggcacg 780 gggggagatc aacttcaagg acattcaggt cattgtgaat gtgccaccta ccatccaggc 840 caggcagaat attgtgaatg ccaccgccaa cctcggccag tccgtcaccc tggtgtgcga 900 tgccgaaggc ttcccagagc ccaccatgag ctggacaaag gatggggaac agatagagca 960 agaggaagac gatgagaagt acatcttcag cgacgatagt tcccagctga ccatcaaaaa 1020 ggtggataag aacgacgagg ctgagtacat ctgcattgct gagaacaagg ctggcgagca 1080 ggatgcgacc atccacctca aagtctttgc aaaacccaaa atcacatatg tagagaacca 1140 gactgccatg gaattagagg agcaggtcac tcttacctgt gaagcctccg gagaccccat 1200 tccctccatc acctggagga cttctacccg gaacatcagc agcgaagaaa aggcttcgtg 1260 gactcgacca gagaagcaag agactctgga tgggcacatg gtggtgcgta gccatgcccg 1320 tgtgtcgtcg ctgaccctga agagcatcca gtacactgat gccggagagt acatctgcac 1380 cgccagcaac accatcggcc aggactccca gtccatgtac cttgaagtgc aatatgcccc 1440 aaagctacag ggccctgtgg ctgtgtacac ttgggagggg aaccaggtga acatcacctg 1500 cgaggtattt gcctatccca gtgccacgat ctcatggttt cgggatggcc agctgctgcc 1560 aagctccaat tacagcaata tcaagatcta caacaccccc tctgccagct atctggaggt 1620 gaccccagac tctgagaatg attttgggaa ctacaactgt actgcagtga accgcattgg 1680 gcaggagtcc ttggaattca tccttgttca agcagacacc ccctcttcac catccatcga 1740 ccaggtggag ccatactcca gcacagccca ggtgcagttt gatgaaccag aggccacagg 1800 tggggtgccc atcctcaaat acaaagctga gtggagagca gttggtgaag aagtatggca 1860 ttccaagtgg tatgatgcca aggaagccag catggagggc atcgtcacca tcgtgggcct 1920 gaagcccgaa acaacgtacg ccgtaaggct ggcggcgctc aatggcaaag ggctgggtga 1980 gatcagcgcg gcctccgagt tcaagacgca gccagtccgg gaacccagtg cacctaagct 2040 cgaagggcag atgggagagg atggaaactc tattaaagtg aacctgatca agcaggatga 2100 cggcggctcc cccatcagac actatctggt caggtaccga gcgctctcct ccgagtggaa 2160 accagagatc aggctcccgt ctggcagtga ccacgtcatg ctgaagtccc tggactggaa 2220 tgctgagtat gaggtctacg tggtggctga gaaccagcaa ggaaaatcca aggcggctca 2280 ttttgtgttc aggacctcgg cccagcccac agccatccca gcaaccttgg gaggcaattc 2340 tgcatcctac acctttgtct cattgctttt ctctgcagtg actcttcttt tgctctgtta 2400 ggaacttgaa cacaaaaatt aaatttgctt aaaagcccag ttcctatgaa aaagatcagt 2460 gccccctttg gaagaacctg gcaggaccac catggccaca gctgctgagc aaccattctg 2520 tgtggaagag aaggttttgt gattggaaaa agctttacct ccagacatgt caccactcac 2580 agatactttt gtgccacttc ataaggagtt tgcccccttt ttaatggcag taaaaagaat 2640 ttgagagctc tttctttaaa tgctattttt aaaaaccatc atgctagatt tacagagaag 2700 tttctgcata tctgctactt gttgcatttt gggttcaaac ctaaatatga tgtagcagag 2760 gaagaattct aagtaccttc taaagcttgt gtcagattgt taaaatcacc acacattccc 2820 ctcattctaa ctctgtgctc cttgtcctcc cttcaataat aattggcttt gcttgcaatt 2880 aagcatttaa gtgcccatgt taaaagagcc agaccgcact gattcacatg agcgttttgc 2940 tgacatgatg ggcaactgaa gtcacccctg ttgcccatgc actggaaaaa aagttgaatt 3000 tgttggatat tttctggggc tgatgaacgt tctgggatgt gctttcagtc ctcgtattac 3060 ggccagcacc ttacactgtc tctgtgaacg gggccaagcc atgatgtgcc aacaagtgtc 3120 agctttgaaa ggtgtttgtc tcccaatcgg ggtgactccc ctgctgcctg gcagcatgtc 3180 gcagatcagc acagagtggg gccgtggttc agcagtgacc cacagaatgg ctttgagcat 3240 cagtctacag gacaggttgg aagcatccac tgtgaaccag gcattagtcc cctacctggc 3300 ctgtgtgtgc tcagtagaga aggagaggga caggccactc ccagactgcc cagcccagga 3360 gggttaataa attggggccg agccaacctg tcagtgcttc ctgaatgccc cagcctctgt 3420 attggtgcgt tggttcagtg acattttcta aactctcctg aaaatccagc tgctcctccc 3480 tgctgcttgg gagttcaccc aggagaggaa atgggtgtgt tttgttaagg tcccttgtgg 3540 agactcaggg ctgaatcctg cttggtaata tcagtgtgtg tgcttgggga tggaccttct 3600 actgaataaa aactccctcc ctccccccat tgtggtcaca tatcattcta catatctcat 3660 ctctgagcat ctccatggaa gcttgatttt tgttcttttt ggtttcttta tgtatttttt 3720 tctgttgtta ttatttttta atgttcaaag actagccttt ccctttggga ttccaaatga 3780 tcccatgctg tggtctgagg ggcaaagcca cctatgttgg cgctcgccat taatccccag 3840 cgctcagttt agaggctcac gtgcagacat cagaggctcc atgctgcaca gtagctcagg 3900 cagggtagtg cctctcaacc cagccacaaa actctccccg ctggagtccc agatggcgct 3960 tcacaccagg gcagtggagg caggcatggt ttttgggcac agggcagagc ataaggatcc 4020 caggtcagtg tgggagagct actggctctt aggatcacct tgggcagaag tcacacggct 4080 tcatcctagg agggcccagc ttgggagtct gcctccccct gatcccagga ccacccacag 4140 gagaggggca gtgtccatct ttctgaaggg accctttgga gatctcgtcc taagtgtgga 4200 gaggactgac gtggccctgt catctcaaca catcccaggg tcaggcaggc ctcagctgaa 4260 acaatgtcag ggtcctcaag ggtcccattt agacagaccc acggcttgta acagtgcgct 4320 cctcaggagg cagcactagc gcatacccac tccccacgga cactgagttc ctggtgacag 4380 ctgcagcccc agccccgcca ggagtcctgg agacagcagc cctcagagac cctgcaggag 4440 tgagtgcacc ccaccttgct cagccacacc ccactcccct gtgccctgta gttgtgctgc 4500 ccatgctcca cacaccatgg ggcccctttg ctcatttttg gactatttat acagcaggtt 4560 tggatcatgt ttttctacta ataagaatgc taacattgtt gtgtagataa tcagtgaggg 4620 ctttatgaag tttacacctt tgcattatta aaggaaataa cagttcatgt gaa 4673 <![CDATA[<210> 125]]> <![CDATA[<211> 5816]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 125]]> actcattctc cgatcagcgc gtgaacgcag ctcggctgcc gctggcagga aacaattctg 60 caaaaataat catactcagc ctggcaattg tctgccccta ggtctgtcgc tcagccgccg 120 tccacactcg ctgcaggggg gggggcacag aatttaccgc ggcaagaaca tccctcccag 180 ccagcagatt acaatgctgc aaactaagga tctcatctgg actttgtttt tcctgggaac 240 tgcagtttct ctgcaggtgg atattgttcc cagccagggg gagatcagcg ttggagagtc 300 caaattcttc ttatgccaag tggcaggaga tgccaaagat aaagacatct cctggttctc 360 ccccaatgga gaaaagctca ccccaaacca gcagcggatc tcagtggtgt ggaatgatga 420 ttcctcctcc accctcacca tctataacgc caacatcgac gacgccggca tttacaagtg 480 tgtggttaca ggcgaggatg gcagtgagtc agaggccacc gtcaacgtga agatctttca 540 gaagctcatg ttcaagaatg cgccaacccc acaggagttc cgggaggggg aagatgccgt 600 gattgtgtgt gatgtggtca gctccctccc accaaccatc atctggaaac acaaaggccg 660 agatgtcatc ctgaaaaaag atgtccgatt catagtcctg tccaacaact acctgcagat 720 ccggggcatc aagaaaacag atgagggcac ttatcgctgt gagggcagaa tcctggcacg 780 gggggagatc aacttcaagg acattcaggt cattgtgaat gtgccaccta ccatccaggc 840 caggcagaat attgtgaatg ccaccgccaa cctcggccag tccgtcaccc tggtgtgcga 900 tgccgaaggc ttcccagagc ccaccatgag ctggacaaag gatggggaac agatagagca 960 agaggaagac gatgagaagt acatcttcag cgacgatagt tcccagctga ccatcaaaaa 1020 ggtggataag aacgacgagg ctgagtacat ctgcattgct gagaacaagg ctggcgagca 1080 ggatgcgacc atccacctca aagtctttgc aaaacccaaa atcacatatg tagagaacca 1140 gactgccatg gaattagagg agcaggtcac tcttacctgt gaagcctccg gagaccccat 1200 tccctccatc acctggagga cttctacccg gaacatcagc agcgaagaaa aggcttcgtg 1260 gactcgacca gagaagcaag agactctgga tgggcacatg gtggtgcgta gccatgcccg 1320 tgtgtcgtcg ctgaccctga agagcatcca gtacactgat gccggagagt acatctgcac 1380 cgccagcaac accatcggcc aggactccca gtccatgtac cttgaagtgc aatatgcccc 1440 aaagctacag ggccctgtgg ctgtgtacac ttgggagggg aaccaggtga acatcacctg 1500 cgaggtattt gcctatccca gtgccacgat ctcatggttt cgggatggcc agctgctgcc 1560 aagctccaat tacagcaata tcaagatcta caacaccccc tctgccagct atctggaggt 1620 gaccccagac tctgagaatg attttgggaa ctacaactgt actgcagtga accgcattgg 1680 gcaggagtcc ttggaattca tccttgttca agcagacacc ccctcttcac catccatcga 1740 ccaggtggag ccatactcca gcacagccca ggtgcagttt gatgaaccag aggccacagg 1800 tggggtgccc atcctcaaat acaaagctga gtggagagca gttggtgaag aagtatggca 1860 ttccaagtgg tatgatgcca aggaagccag catggagggc atcgtcacca tcgtgggcct 1920 gaagcccgaa acaacgtacg ccgtaaggct ggcggcgctc aatggcaaag ggctgggtga 1980 gatcagcgcg gcctccgagt tcaagacgca gccagtccgg gaacccagtg cacctaagct 2040 cgaagggcag atgggagagg atggaaactc tattaaagtg aacctgatca agcaggatga 2100 cggcggctcc cccatcagac actatctggt caggtaccga gcgctctcct ccgagtggaa 2160 accagagatc aggctcccgt ctggcagtga ccacgtcatg ctgaagtccc tggactggaa 2220 tgctgagtat gaggtctacg tggtggctga gaaccagcaa ggaaaatcca aggcggctca 2280 ttttgtgttc aggacctcgg cccagcccac agccatccca gccaacggca gccccacctc 2340 aggcctgagc accggggcca tcgtgggcat cctcatcgtc atcttcgtcc tgctcctggt 2400 ggttgtggac atcacctgct acttcctgaa caagtgtggc ctgttcatgt gcattgcggt 2460 caacctgtgt ggaaaagccg ggcccggggc caagggcaag gacatggagg agggcaaggc 2520 cgccttctcg aaagatgagt ccaaggagcc catcgtggag gttcgaacgg aggaggagag 2580 gaccccaaac catgatggag ggaaacacac agagcccaac gagaccacgc cactgacgga 2640 gcccgagaag ggccccgtag aagcaaagcc agagtgccag gagacagaaa cgaagccagc 2700 gccagccgaa gtcaagacgg tccccaatga cgccacacag acaaaggaga acgagagcaa 2760 agcatgatgg gtgaagagaa ccgagcaaag atcaaaataa aaagtgacac agcagcttca 2820 ccagagcatt tccaacacca cagacacaca cacgcacgca cacacacaaa cacacatgca 2880 cacacacaca tctcatttct ctagtgtctt ttgcctttaa aaaaaactaa acagataaaa 2940 catgggaatc tcctttttgt aggtttatag aaagggtccc tttgttgcac actcacttgt 3000 aagaaaatga gacaaaaagg ttaaacccac agccaaacta ggacactccg ttccctgaaa 3060 ccgttaaaaa atcaaacaaa aggaccccaa attaagaatc taggaagctc agaaacgaaa 3120 tctaggttca ggaagaccac acttggtgtt acccgattgg cacagaccag tttcagagaa 3180 atactttcag gcactaagac taatcgaatg aacaaagtcc acagtttatt tttatacttt 3240 cagtcaagtt tgaactctgt aaaacctcat aaataagtta taatttctgt tcactttgta 3300 tttgttcagt atgcaaagtg tgtcaccctt tctagctgaa ttcaattccc acgtagactc 3360 ttattttata ggacgaatgc caaattgcag cttctggggg tagatctcaa tttgcagtat 3420 tcagacttct ttttctttct tttacattct tttttctttc tttctttctg ccaactttgt 3480 tttccagtgt ttacaaggtg acaaatgttt gactttggtt gtgtttaaat gtccgtgtaa 3540 aatagctgcc ttttattttt taaggtaaca aataccacct agaggtaggt aggatcatcc 3600 cacgcttgct ttagcacagg acaactttac aaaacatgat tgtttacagc tgctcttccc 3660 ctcttttctg atctgcagtt tttgcctggg tcccactcag gtgaaaatcc atctcattct 3720 ggaatggttt tgcttttgaa tttttggtta tttttgtgtt tctttggggg ttagaccact 3780 ttctgattag ccgccacctg cctgcatctg tgaaaaggga tctgctccca ggcgttctca 3840 cccttctttt gaaggactcc ttaggctttg ttgaatgaag cagagaagat tgtatagttg 3900 gggctggtct tggtgaacac acattattac cccacacatc ccctttgtgt agaaagccaa 3960 ataaaatcta tacataccat ttccttttga gcccagaatc tagatttgag cggaagagca 4020 tgtgtgcttc agggaattag tgtctttttt tggaaatctg ttgaagtaaa gtaacatcgg 4080 ccttctgttc acttaggcag catttataga aacaaaagaa gaaagaaaca acctactgtc 4140 tggagtcata acacaacttt cctggattgg aaaccaagtg ggggaaaaaa tacagaaact 4200 ttaaggggga tgggaggggg gggagaaggg aaaagccagc cctttgtata gaaattttgc 4260 ttttttttcc ctcattctac tttagaactg caagcttgtg cactgtggat gcgtgaatat 4320 tttagtgtga aacgtgtttt tgtcatagta ttgaaataaa acttcaacat agtttggttg 4380 tggaaggtat agcagatagt tcagaaaaaa tattcaggaa acaaaaatca ctcaaacgga 4440 atcgaagcct tttaacaaag aaaatgaaat acagatgatg atgatgatga tgaagatgat 4500 gctaagtaaa cagaaatcag tactccgcat gcgctcctct cctaaggtac aaagcagcaa 4560 gaggttaggg tggcaaggct gcctctgggt ccattctgtg ggccactctc cccaacgttc 4620 tgacacttct gcagtctgat cagtggcgat gctagattat aatttcaaac tgtgaagaat 4680 aatggtcttg tcatttgctc aatgtggggt tatgttgcat tttctcagct cctggggatg 4740 gaaatggagg atcccagaac acacagccct ggcccctttg attctagggc ctgcacagat 4800 ctctggttca aatgcacagg ccctcagaat agaggaacat gaagagagat cttagagcac 4860 acagtagaat gtgagagcct gggtgtctga gaccgggagg gcccagcagt gaggggcagg 4920 ctcttctggt caccaggctg ttcagtggac tcagttcttc atcttgtaat gtcgatggct 4980 ttgccacacc aggccaagcc catgccatac cttgtcaaga ctgtcaaagt ggttgtggtt 5040 aggtcaaact ggttttggtt ctgatggtta ggaagaaaca ggtcagccct cagatcacct 5100 ggcccgggac agctgacccc ctagaaccct ggctctgcca ttagctagga cctaagactc 5160 tgcccacatt ttggtctgtt ctctcccatt acacataggt ttgtctcagc atgcaagagt 5220 ttttccttta aaaaaaaaaa aaaaaaaaaa aaaaaagcaa tgctttctct aaaatcaaag 5280 agggagtcat tttattccaa gatgttttat cttttatgtt aagagatcaa agcttataat 5340 tttctttttt aatttttgaa ggagggatca actccagttt ccaatgtcta tgtgtctatg 5400 tgtgtatgtg ccatacatat gtattcacat gaagaccggc atggccaagt tctgctggag 5460 gagcactcaa gtgtgacgag cagggccact ggaccctgca gggctgtggt gtatatagtg 5520 cagctttgga ggtggaactc tattttcaca cttttctatg gagccttccg agtcccaggt 5580 tttcacttga ggctgtctgt ctggatggcg gttttcagac ctccattaac atccctaccc 5640 agcattctgt acttcggggg ccttctctct tgttataaaa ctttttacca agtgaaacat 5700 cgataccacc tttgtttcca ttctcactgg tgtaaatact gagtactaac tgagaatttt 5760 gactttgcat tctgtcggaa tacttgtgtt caataaaaat tgaaagaaaa aagcta 5816 <![CDATA[<210> 126]]> <![CDATA[<211> 4643]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 126]]> actcattctc cgatcagcgc gtgaacgcag ctcggctgcc gctggcagga aacaattctg 60 caaaaataat catactcagc ctggcaattg tctgccccta ggtctgtcgc tcagccgccg 120 tccacactcg ctgcaggggg gggggcacag aatttaccgc ggcaagaaca tccctcccag 180 ccagcagatt acaatgctgc aaactaagga tctcatctgg actttgtttt tcctgggaac 240 tgcagtttct ctgcaggtgg atattgttcc cagccagggg gagatcagcg ttggagagtc 300 caaattcttc ttatgccaag tggcaggaga tgccaaagat aaagacatct cctggttctc 360 ccccaatgga gaaaagctca ccccaaacca gcagcggatc tcagtggtgt ggaatgatga 420 ttcctcctcc accctcacca tctataacgc caacatcgac gacgccggca tttacaagtg 480 tgtggttaca ggcgaggatg gcagtgagtc agaggccacc gtcaacgtga agatctttca 540 gaagctcatg ttcaagaatg cgccaacccc acaggagttc cgggaggggg aagatgccgt 600 gattgtgtgt gatgtggtca gctccctccc accaaccatc atctggaaac acaaaggccg 660 agatgtcatc ctgaaaaaag atgtccgatt catagtcctg tccaacaact acctgcagat 720 ccggggcatc aagaaaacag atgagggcac ttatcgctgt gagggcagaa tcctggcacg 780 gggggagatc aacttcaagg acattcaggt cattgtgaat gtgccaccta ccatccaggc 840 caggcagaat attgtgaatg ccaccgccaa cctcggccag tccgtcaccc tggtgtgcga 900 tgccgaaggc ttcccagagc ccaccatgag ctggacaaag gatggggaac agatagagca 960 agaggaagac gatgagaagt acatcttcag cgacgatagt tcccagctga ccatcaaaaa 1020 ggtggataag aacgacgagg ctgagtacat ctgcattgct gagaacaagg ctggcgagca 1080 ggatgcgacc atccacctca aagtctttgc aaaacccaaa atcacatatg tagagaacca 1140 gactgccatg gaattagagg agcaggtcac tcttacctgt gaagcctccg gagaccccat 1200 tccctccatc acctggagga cttctacccg gaacatcagc agcgaagaaa agactctgga 1260 tgggcacatg gtggtgcgta gccatgcccg tgtgtcgtcg ctgaccctga agagcatcca 1320 gtacactgat gccggagagt acatctgcac cgccagcaac accatcggcc aggactccca 1380 gtccatgtac cttgaagtgc aatatgcccc aaagctacag ggccctgtgg ctgtgtacac 1440 ttgggagggg aaccaggtga acatcacctg cgaggtattt gcctatccca gtgccacgat 1500 ctcatggttt cgggatggcc agctgctgcc aagctccaat tacagcaata tcaagatcta 1560 caacaccccc tctgccagct atctggaggt gaccccagac tctgagaatg attttgggaa 1620 ctacaactgt actgcagtga accgcattgg gcaggagtcc ttggaattca tccttgttca 1680 agcagacacc ccctcttcac catccatcga ccaggtggag ccatactcca gcacagccca 1740 ggtgcagttt gatgaaccag aggccacagg tggggtgccc atcctcaaat acaaagctga 1800 gtggagagca gttggtgaag aagtatggca ttccaagtgg tatgatgcca aggaagccag 1860 catggagggc atcgtcacca tcgtgggcct gaagcccgaa acaacgtacg ccgtaaggct 1920 ggcggcgctc aatggcaaag ggctgggtga gatcagcgcg gcctccgagt tcaagacgca 1980 gccagtccgg gaacccagtg cacctaagct cgaagggcag atgggagagg atggaaactc 2040 tattaaagtg aacctgatca agcaggatga cggcggctcc cccatcagac actatctggt 2100 caggtaccga gcgctctcct ccgagtggaa accagagatc aggctcccgt ctggcagtga 2160 ccacgtcatg ctgaagtccc tggactggaa tgctgagtat gaggtctacg tggtggctga 2220 gaaccagcaa ggaaaatcca aggcggctca ttttgtgttc aggacctcgg cccagcccac 2280 agccatccca gcaaccttgg gaggcaattc tgcatcctac acctttgtct cattgctttt 2340 ctctgcagtg actcttcttt tgctctgtta ggaacttgaa cacaaaaatt aaatttgctt 2400 aaaagcccag ttcctatgaa aaagatcagt gccccctttg gaagaacctg gcaggaccac 2460 catggccaca gctgctgagc aaccattctg tgtggaagag aaggttttgt gattggaaaa 2520 agctttacct ccagacatgt caccactcac agatactttt gtgccacttc ataaggagtt 2580 tgcccccttt ttaatggcag taaaaagaat ttgagagctc tttctttaaa tgctattttt 2640 aaaaaccatc atgctagatt tacagagaag tttctgcata tctgctactt gttgcatttt 2700 gggttcaaac ctaaatatga tgtagcagag gaagaattct aagtaccttc taaagcttgt 2760 gtcagattgt taaaatcacc acacattccc ctcattctaa ctctgtgctc cttgtcctcc 2820 cttcaataat aattggcttt gcttgcaatt aagcatttaa gtgcccatgt taaaagagcc 2880 agaccgcact gattcacatg agcgttttgc tgacatgatg ggcaactgaa gtcacccctg 2940 ttgcccatgc actggaaaaa aagttgaatt tgttggatat tttctggggc tgatgaacgt 3000 tctgggatgt gctttcagtc ctcgtattac ggccagcacc ttacactgtc tctgtgaacg 3060 gggccaagcc atgatgtgcc aacaagtgtc agctttgaaa ggtgtttgtc tcccaatcgg 3120 ggtgactccc ctgctgcctg gcagcatgtc gcagatcagc acagagtggg gccgtggttc 3180 agcagtgacc cacagaatgg ctttgagcat cagtctacag gacaggttgg aagcatccac 3240 tgtgaaccag gcattagtcc cctacctggc ctgtgtgtgc tcagtagaga aggagaggga 3300 caggccactc ccagactgcc cagcccagga gggttaataa attggggccg agccaacctg 3360 tcagtgcttc ctgaatgccc cagcctctgt attggtgcgt tggttcagtg acattttcta 3420 aactctcctg aaaatccagc tgctcctccc tgctgcttgg gagttcaccc aggagaggaa 3480 atgggtgtgt tttgttaagg tcccttgtgg agactcaggg ctgaatcctg cttggtaata 3540 tcagtgtgtg tgcttgggga tggaccttct actgaataaa aactccctcc ctccccccat 3600 tgtggtcaca tatcattcta catatctcat ctctgagcat ctccatggaa gcttgatttt 3660 tgttcttttt ggtttcttta tgtatttttt tctgttgtta ttatttttta atgttcaaag 3720 actagccttt ccctttggga ttccaaatga tcccatgctg tggtctgagg ggcaaagcca 3780 cctatgttgg cgctcgccat taatccccag cgctcagttt agaggctcac gtgcagacat 3840 cagaggctcc atgctgcaca gtagctcagg cagggtagtg cctctcaacc cagccacaaa 3900 actctccccg ctggagtccc agatggcgct tcacaccagg gcagtggagg caggcatggt 3960 ttttgggcac agggcagagc ataaggatcc caggtcagtg tgggagagct actggctctt 4020 aggatcacct tgggcagaag tcacacggct tcatcctagg agggcccagc ttgggagtct 4080 gcctccccct gatcccagga ccacccacag gagaggggca gtgtccatct ttctgaaggg 4140 accctttgga gatctcgtcc taagtgtgga gaggactgac gtggccctgt catctcaaca 4200 catcccaggg tcaggcaggc ctcagctgaa acaatgtcag ggtcctcaag ggtcccattt 4260 agacagaccc acggcttgta acagtgcgct cctcaggagg cagcactagc gcatacccac 4320 tccccacgga cactgagttc ctggtgacag ctgcagcccc agccccgcca ggagtcctgg 4380 agacagcagc cctcagagac cctgcaggag tgagtgcacc ccaccttgct cagccacacc 4440 ccactcccct gtgccctgta gttgtgctgc ccatgctcca cacaccatgg ggcccctttg 4500 ctcatttttg gactatttat acagcaggtt tggatcatgt ttttctacta ataagaatgc 4560 taacattgtt gtgtagataa tcagtgaggg ctttatgaag tttacacctt tgcattatta 4620 aaggaaataa cagttcatgt gaa 4643 <![CDATA[<210> 127]]> <![CDATA[<211> 5786]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 127]]> actcattctc cgatcagcgc gtgaacgcag ctcggctgcc gctggcagga aacaattctg 60 caaaaataat catactcagc ctggcaattg tctgccccta ggtctgtcgc tcagccgccg 120 tccacactcg ctgcaggggg gggggcacag aatttaccgc ggcaagaaca tccctcccag 180 ccagcagatt acaatgctgc aaactaagga tctcatctgg actttgtttt tcctgggaac 240 tgcagtttct ctgcaggtgg atattgttcc cagccagggg gagatcagcg ttggagagtc 300 caaattcttc ttatgccaag tggcaggaga tgccaaagat aaagacatct cctggttctc 360 ccccaatgga gaaaagctca ccccaaacca gcagcggatc tcagtggtgt ggaatgatga 420 ttcctcctcc accctcacca tctataacgc caacatcgac gacgccggca tttacaagtg 480 tgtggttaca ggcgaggatg gcagtgagtc agaggccacc gtcaacgtga agatctttca 540 gaagctcatg ttcaagaatg cgccaacccc acaggagttc cgggaggggg aagatgccgt 600 gattgtgtgt gatgtggtca gctccctccc accaaccatc atctggaaac acaaaggccg 660 agatgtcatc ctgaaaaaag atgtccgatt catagtcctg tccaacaact acctgcagat 720 ccggggcatc aagaaaacag atgagggcac ttatcgctgt gagggcagaa tcctggcacg 780 gggggagatc aacttcaagg acattcaggt cattgtgaat gtgccaccta ccatccaggc 840 caggcagaat attgtgaatg ccaccgccaa cctcggccag tccgtcaccc tggtgtgcga 900 tgccgaaggc ttcccagagc ccaccatgag ctggacaaag gatggggaac agatagagca 960 agaggaagac gatgagaagt acatcttcag cgacgatagt tcccagctga ccatcaaaaa 1020 ggtggataag aacgacgagg ctgagtacat ctgcattgct gagaacaagg ctggcgagca 1080 ggatgcgacc atccacctca aagtctttgc aaaacccaaa atcacatatg tagagaacca 1140 gactgccatg gaattagagg agcaggtcac tcttacctgt gaagcctccg gagaccccat 1200 tccctccatc acctggagga cttctacccg gaacatcagc agcgaagaaa agactctgga 1260 tgggcacatg gtggtgcgta gccatgcccg tgtgtcgtcg ctgaccctga agagcatcca 1320 gtacactgat gccggagagt acatctgcac cgccagcaac accatcggcc aggactccca 1380 gtccatgtac cttgaagtgc aatatgcccc aaagctacag ggccctgtgg ctgtgtacac 1440 ttgggagggg aaccaggtga acatcacctg cgaggtattt gcctatccca gtgccacgat 1500 ctcatggttt cgggatggcc agctgctgcc aagctccaat tacagcaata tcaagatcta 1560 caacaccccc tctgccagct atctggaggt gaccccagac tctgagaatg attttgggaa 1620 ctacaactgt actgcagtga accgcattgg gcaggagtcc ttggaattca tccttgttca 1680 agcagacacc ccctcttcac catccatcga ccaggtggag ccatactcca gcacagccca 1740 ggtgcagttt gatgaaccag aggccacagg tggggtgccc atcctcaaat acaaagctga 1800 gtggagagca gttggtgaag aagtatggca ttccaagtgg tatgatgcca aggaagccag 1860 catggagggc atcgtcacca tcgtgggcct gaagcccgaa acaacgtacg ccgtaaggct 1920 ggcggcgctc aatggcaaag ggctgggtga gatcagcgcg gcctccgagt tcaagacgca 1980 gccagtccgg gaacccagtg cacctaagct cgaagggcag atgggagagg atggaaactc 2040 tattaaagtg aacctgatca agcaggatga cggcggctcc cccatcagac actatctggt 2100 caggtaccga gcgctctcct ccgagtggaa accagagatc aggctcccgt ctggcagtga 2160 ccacgtcatg ctgaagtccc tggactggaa tgctgagtat gaggtctacg tggtggctga 2220 gaaccagcaa ggaaaatcca aggcggctca ttttgtgttc aggacctcgg cccagcccac 2280 agccatccca gccaacggca gccccacctc aggcctgagc accggggcca tcgtgggcat 2340 cctcatcgtc atcttcgtcc tgctcctggt ggttgtggac atcacctgct acttcctgaa 2400 caagtgtggc ctgttcatgt gcattgcggt caacctgtgt ggaaaagccg ggcccggggc 2460 caagggcaag gacatggagg agggcaaggc cgccttctcg aaagatgagt ccaaggagcc 2520 catcgtggag gttcgaacgg aggaggagag gaccccaaac catgatggag ggaaacacac 2580 agagcccaac gagaccacgc cactgacgga gcccgagaag ggccccgtag aagcaaagcc 2640 agagtgccag gagacagaaa cgaagccagc gccagccgaa gtcaagacgg tccccaatga 2700 cgccacacag acaaaggaga acgagagcaa agcatgatgg gtgaagagaa ccgagcaaag 2760 atcaaaataa aaagtgacac agcagcttca ccagagcatt tccaacacca cagacacaca 2820 cacgcacgca cacacacaaa cacacatgca cacacacaca tctcatttct ctagtgtctt 2880 ttgcctttaa aaaaaactaa acagataaaa catgggaatc tcctttttgt aggtttatag 2940 aaagggtccc tttgttgcac actcacttgt aagaaaatga gacaaaaagg ttaaacccac 3000 agccaaacta ggacactccg ttccctgaaa ccgttaaaaa atcaaacaaa aggaccccaa 3060 attaagaatc taggaagctc agaaacgaaa tctaggttca ggaagaccac acttggtgtt 3120 acccgattgg cacagaccag tttcagagaa atactttcag gcactaagac taatcgaatg 3180 aacaaagtcc acagtttatt tttatacttt cagtcaagtt tgaactctgt aaaacctcat 3240 aaataagtta taatttctgt tcactttgta tttgttcagt atgcaaagtg tgtcaccctt 3300 tctagctgaa ttcaattccc acgtagactc ttattttata ggacgaatgc caaattgcag 3360 cttctggggg tagatctcaa tttgcagtat tcagacttct ttttctttct tttacattct 3420 tttttctttc tttctttctg ccaactttgt tttccagtgt ttacaaggtg acaaatgttt 3480 gactttggtt gtgtttaaat gtccgtgtaa aatagctgcc ttttattttt taaggtaaca 3540 aataccacct agaggtaggt aggatcatcc cacgcttgct ttagcacagg acaactttac 3600 aaaacatgat tgtttacagc tgctcttccc ctcttttctg atctgcagtt tttgcctggg 3660 tcccactcag gtgaaaatcc atctcattct ggaatggttt tgcttttgaa tttttggtta 3720 tttttgtgtt tctttggggg ttagaccact ttctgattag ccgccacctg cctgcatctg 3780 tgaaaaggga tctgctccca ggcgttctca cccttctttt gaaggactcc ttaggctttg 3840 ttgaatgaag cagagaagat tgtatagttg gggctggtct tggtgaacac acattattac 3900 cccacacatc ccctttgtgt agaaagccaa ataaaatcta tacataccat ttccttttga 3960 gcccagaatc tagatttgag cggaagagca tgtgtgcttc agggaattag tgtctttttt 4020 tggaaatctg ttgaagtaaa gtaacatcgg ccttctgttc acttaggcag catttataga 4080 aacaaaagaa gaaagaaaca acctactgtc tggagtcata acacaacttt cctggattgg 4140 aaaccaagtg ggggaaaaaa tacagaaact ttaaggggga tgggaggggg gggagaaggg 4200 aaaagccagc cctttgtata gaaattttgc ttttttttcc ctcattctac tttagaactg 4260 caagcttgtg cactgtggat gcgtgaatat tttagtgtga aacgtgtttt tgtcatagta 4320 ttgaaataaa acttcaacat agtttggttg tggaaggtat agcagatagt tcagaaaaaa 4380 tattcaggaa acaaaaatca ctcaaacgga atcgaagcct tttaacaaag aaaatgaaat 4440 acagatgatg atgatgatga tgaagatgat gctaagtaaa cagaaatcag tactccgcat 4500 gcgctcctct cctaaggtac aaagcagcaa gaggttaggg tggcaaggct gcctctgggt 4560 ccattctgtg ggccactctc cccaacgttc tgacacttct gcagtctgat cagtggcgat 4620 gctagattat aatttcaaac tgtgaagaat aatggtcttg tcatttgctc aatgtggggt 4680 tatgttgcat tttctcagct cctggggatg gaaatggagg atcccagaac acacagccct 4740 ggcccctttg attctagggc ctgcacagat ctctggttca aatgcacagg ccctcagaat 4800 agaggaacat gaagagagat cttagagcac acagtagaat gtgagagcct gggtgtctga 4860 gaccgggagg gcccagcagt gaggggcagg ctcttctggt caccaggctg ttcagtggac 4920 tcagttcttc atcttgtaat gtcgatggct ttgccacacc aggccaagcc catgccatac 4980 cttgtcaaga ctgtcaaagt ggttgtggtt aggtcaaact ggttttggtt ctgatggtta 5040 ggaagaaaca ggtcagccct cagatcacct ggcccgggac agctgacccc ctagaaccct 5100 ggctctgcca ttagctagga cctaagactc tgcccacatt ttggtctgtt ctctcccatt 5160 acacataggt ttgtctcagc atgcaagagt ttttccttta aaaaaaaaaa aaaaaaaaaa 5220 aaaaaagcaa tgctttctct aaaatcaaag agggagtcat tttattccaa gatgttttat 5280 cttttatgtt aagagatcaa agcttataat tttctttttt aatttttgaa ggagggatca 5340 actccagttt ccaatgtcta tgtgtctatg tgtgtatgtg ccatacatat gtattcacat 5400 gaagaccggc atggccaagt tctgctggag gagcactcaa gtgtgacgag cagggccact 5460 ggaccctgca gggctgtggt gtatatagtg cagctttgga ggtggaactc tattttcaca 5520 cttttctatg gagccttccg agtcccaggt tttcacttga ggctgtctgt ctggatggcg 5580 gttttcagac ctccattaac atccctaccc agcattctgt acttcggggg ccttctctct 5640 tgttataaaa ctttttacca agtgaaacat cgataccacc tttgtttcca ttctcactgg 5700 tgtaaatact gagtactaac tgagaatttt gactttgcat tctgtcggaa tacttgtgtt 5760 caataaaaat tgaaagaaaa aagcta 5786 <![CDATA[<210> 128]]> <![CDATA[<211> 5819]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 128]]> actcattctc cgatcagcgc gtgaacgcag ctcggctgcc gctggcagga aacaattctg 60 caaaaataat catactcagc ctggcaattg tctgccccta ggtctgtcgc tcagccgccg 120 tccacactcg ctgcaggggg gggggcacag aatttaccgc ggcaagaaca tccctcccag 180 ccagcagatt acaatgctgc aaactaagga tctcatctgg actttgtttt tcctgggaac 240 tgcagtttct ctgcaggtgg atattgttcc cagccagggg gagatcagcg ttggagagtc 300 caaattcttc ttatgccaag tggcaggaga tgccaaagat aaagacatct cctggttctc 360 ccccaatgga gaaaagctca ccccaaacca gcagcggatc tcagtggtgt ggaatgatga 420 ttcctcctcc accctcacca tctataacgc caacatcgac gacgccggca tttacaagtg 480 tgtggttaca ggcgaggatg gcagtgagtc agaggccacc gtcaacgtga agatctttca 540 gaagctcatg ttcaagaatg cgccaacccc acaggagttc cgggaggggg aagatgccgt 600 gattgtgtgt gatgtggtca gctccctccc accaaccatc atctggaaac acaaaggccg 660 agatgtcatc ctgaaaaaag atgtccgatt catagtcctg tccaacaact acctgcagat 720 ccggggcatc aagaaaacag atgagggcac ttatcgctgt gagggcagaa tcctggcacg 780 gggggagatc aacttcaagg acattcaggt cattgtgaat gtgccaccta ccatccaggc 840 caggcagaat attgtgaatg ccaccgccaa cctcggccag tccgtcaccc tggtgtgcga 900 tgccgaaggc ttcccagagc ccaccatgag ctggacaaag gatggggaac agatagagca 960 agaggaagac gatgagaagt acatcttcag cgacgatagt tcccagctga ccatcaaaaa 1020 ggtggataag aacgacgagg ctgagtacat ctgcattgct gagaacaagg ctggcgagca 1080 ggatgcgacc atccacctca aagtctttgc aaaacccaaa atcacatatg tagagaacca 1140 gactgccatg gaattagagg agcaggtcac tcttacctgt gaagcctccg gagaccccat 1200 tccctccatc acctggagga cttctacccg gaacatcagc agcgaagaaa aggcttcgtg 1260 gactcgacca gagaagcaag agactctgga tgggcacatg gtggtgcgta gccatgcccg 1320 tgtgtcgtcg ctgaccctga agagcatcca gtacactgat gccggagagt acatctgcac 1380 cgccagcaac accatcggcc aggactccca gtccatgtac cttgaagtgc aatatgcccc 1440 aaagctacag ggccctgtgg ctgtgtacac ttgggagggg aaccaggtga acatcacctg 1500 cgaggtattt gcctatccca gtgccacgat ctcatggttt cgggatggcc agctgctgcc 1560 aagctccaat tacagcaata tcaagatcta caacaccccc tctgccagct atctggaggt 1620 gaccccagac tctgagaatg attttgggaa ctacaactgt actgcagtga accgcattgg 1680 gcaggagtcc ttggaattca tccttgttca agcagacacc ccctcttcac catccatcga 1740 ccaggtggag ccatactcca gcacagccca ggtgcagttt gatgaaccag aggccacagg 1800 tggggtgccc atcctcaaat acaaagctga gtggagagca gttggtgaag aagtatggca 1860 ttccaagtgg tatgatgcca aggaagccag catggagggc atcgtcacca tcgtgggcct 1920 gaagcccgaa acaacgtacg ccgtaaggct ggcggcgctc aatggcaaag ggctgggtga 1980 gatcagcgcg gcctccgagt tcaagacgca gccagtccaa ggggaaccca gtgcacctaa 2040 gctcgaaggg cagatgggag aggatggaaa ctctattaaa gtgaacctga tcaagcagga 2100 tgacggcggc tcccccatca gacactatct ggtcaggtac cgagcgctct cctccgagtg 2160 gaaaccagag atcaggctcc cgtctggcag tgaccacgtc atgctgaagt ccctggactg 2220 gaatgctgag tatgaggtct acgtggtggc tgagaaccag caaggaaaat ccaaggcggc 2280 tcattttgtg ttcaggacct cggcccagcc cacagccatc ccagccaacg gcagccccac 2340 ctcaggcctg agcaccgggg ccatcgtggg catcctcatc gtcatcttcg tcctgctcct 2400 ggtggttgtg gacatcacct gctacttcct gaacaagtgt ggcctgttca tgtgcattgc 2460 ggtcaacctg tgtggaaaag ccgggcccgg ggccaagggc aaggacatgg aggagggcaa 2520 ggccgccttc tcgaaagatg agtccaagga gcccatcgtg gaggttcgaa cggaggagga 2580 gaggacccca aaccatgatg gagggaaaca cacagagccc aacgagacca cgccactgac 2640 ggagcccgag aagggccccg tagaagcaaa gccagagtgc caggagacag aaacgaagcc 2700 agcgccagcc gaagtcaaga cggtccccaa tgacgccaca cagacaaagg agaacgagag 2760 caaagcatga tgggtgaaga gaaccgagca aagatcaaaa taaaaagtga cacagcagct 2820 tcaccagagc atttccaaca ccacagacac acacacgcac gcacacacac aaacacacat 2880 gcacacacac acatctcatt tctctagtgt cttttgcctt taaaaaaaac taaacagata 2940 aaacatggga atctcctttt tgtaggttta tagaaagggt ccctttgttg cacactcact 3000 tgtaagaaaa tgagacaaaa aggttaaacc cacagccaaa ctaggacact ccgttccctg 3060 aaaccgttaa aaaatcaaac aaaaggaccc caaattaaga atctaggaag ctcagaaacg 3120 aaatctaggt tcaggaagac cacacttggt gttacccgat tggcacagac cagtttcaga 3180 gaaatacttt caggcactaa gactaatcga atgaacaaag tccacagttt atttttatac 3240 tttcagtcaa gtttgaactc tgtaaaacct cataaataag ttataatttc tgttcacttt 3300 gtatttgttc agtatgcaaa gtgtgtcacc ctttctagct gaattcaatt cccacgtaga 3360 ctcttatttt ataggacgaa tgccaaattg cagcttctgg gggtagatct caatttgcag 3420 tattcagact tctttttctt tcttttacat tcttttttct ttctttcttt ctgccaactt 3480 tgttttccag tgtttacaag gtgacaaatg tttgactttg gttgtgttta aatgtccgtg 3540 taaaatagct gccttttatt ttttaaggta acaaatacca cctagaggta ggtaggatca 3600 tcccacgctt gctttagcac aggacaactt tacaaaacat gattgtttac agctgctctt 3660 cccctctttt ctgatctgca gtttttgcct gggtcccact caggtgaaaa tccatctcat 3720 tctggaatgg ttttgctttt gaatttttgg ttatttttgt gtttctttgg gggttagacc 3780 actttctgat tagccgccac ctgcctgcat ctgtgaaaag ggatctgctc ccaggcgttc 3840 tcacccttct tttgaaggac tccttaggct ttgttgaatg aagcagagaa gattgtatag 3900 ttggggctgg tcttggtgaa cacacattat taccccacac atcccctttg tgtagaaagc 3960 caaataaaat ctatacatac catttccttt tgagcccaga atctagattt gagcggaaga 4020 gcatgtgtgc ttcagggaat tagtgtcttt ttttggaaat ctgttgaagt aaagtaacat 4080 cggccttctg ttcacttagg cagcatttat agaaacaaaa gaagaaagaa acaacctact 4140 gtctggagtc ataacacaac tttcctggat tggaaaccaa gtgggggaaa aaatacagaa 4200 actttaaggg ggatgggagg ggggggagaa gggaaaagcc agccctttgt atagaaattt 4260 tgcttttttt tccctcattc tactttagaa ctgcaagctt gtgcactgtg gatgcgtgaa 4320 tattttagtg tgaaacgtgt ttttgtcata gtattgaaat aaaacttcaa catagtttgg 4380 ttgtggaagg tatagcagat agttcagaaa aaatattcag gaaacaaaaa tcactcaaac 4440 ggaatcgaag ccttttaaca aagaaaatga aatacagatg atgatgatga tgatgaagat 4500 gatgctaagt aaacagaaat cagtactccg catgcgctcc tctcctaagg tacaaagcag 4560 caagaggtta gggtggcaag gctgcctctg ggtccattct gtgggccact ctccccaacg 4620 ttctgacact tctgcagtct gatcagtggc gatgctagat tataatttca aactgtgaag 4680 aataatggtc ttgtcatttg ctcaatgtgg ggttatgttg cattttctca gctcctgggg 4740 atggaaatgg aggatcccag aacacacagc cctggcccct ttgattctag ggcctgcaca 4800 gatctctggt tcaaatgcac aggccctcag aatagaggaa catgaagaga gatcttagag 4860 cacacagtag aatgtgagag cctgggtgtc tgagaccggg agggcccagc agtgaggggc 4920 aggctcttct ggtcaccagg ctgttcagtg gactcagttc ttcatcttgt aatgtcgatg 4980 gctttgccac accaggccaa gcccatgcca taccttgtca agactgtcaa agtggttgtg 5040 gttaggtcaa actggttttg gttctgatgg ttaggaagaa acaggtcagc cctcagatca 5100 cctggcccgg gacagctgac cccctagaac cctggctctg ccattagcta ggacctaaga 5160 ctctgcccac attttggtct gttctctccc attacacata ggtttgtctc agcatgcaag 5220 agtttttcct ttaaaaaaaa aaaaaaaaaa aaaaaaaaag caatgctttc tctaaaatca 5280 aagagggagt cattttattc caagatgttt tatcttttat gttaagagat caaagcttat 5340 aattttcttt tttaattttt gaaggaggga tcaactccag tttccaatgt ctatgtgtct 5400 atgtgtgtat gtgccataca tatgtattca catgaagacc ggcatggcca agttctgctg 5460 gaggagcact caagtgtgac gagcagggcc actggaccct gcagggctgt ggtgtatata 5520 gtgcagcttt ggaggtggaa ctctattttc acacttttct atggagcctt ccgagtccca 5580 ggttttcact tgaggctgtc tgtctggatg gcggttttca gacctccatt aacatcccta 5640 cccagcattc tgtacttcgg gggccttctc tcttgttata aaacttttta ccaagtgaaa 5700 catcgatacc acctttgttt ccattctcac tggtgtaaat actgagtact aactgagaat 5760 tttgactttg cattctgtcg gaatacttgt gttcaataaa aattgaaaga aaaaagcta 5819 <![CDATA[<210> 129]]> <![CDATA[<211> 3908]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 129]]> caaaagaact ttatccctgc tttcattctg acatacctat tatgactttg ttcactaagc 60 agaaggaatt atgggaaatg gaaacttgat ggcatgtttt tattaaggcg ttatgtgtgt 120 atcttcactg agaaattaaa gaaccaagca gaattgtatg ttttcctttc agtgaagttt 180 agcaactgca atggaaaaag aaaagtacaa tatgagagca gtgagcctgc agattttaag 240 gtggatgaag atggcatggt gtatgccgtg agaagctttc cactctcttc tgagcatgcc 300 aagttcctga tatatgccca agacaaagag acccaggaaa agtggcaagt ggcagtaaaa 360 ttgagcctga agccaacctt aactgaggag tcagtgaagg agtcagcaga agttgaagaa 420 atagtgttcc caagacaatt cagtaagcac agtggccacc tacaaaggca gaagagagac 480 tgggtcatcc ctccaatcaa cttgccagaa aactccaggg gaccttttcc tcaagagctt 540 gtcaggatca ggtctgatag agataaaaac ctttcactgc ggtacagtgt aactgggcca 600 ggagctgacc agcctccaac tggtatcttc attatcaacc ccatctcggg tcagctgtcg 660 gtgacaaagc ccctggatcg cgagcagata gcccggtttc atttgagggc acatgcagta 720 gatattaatg gaaatcaagt ggagaacccc attgacattg tcatcaatgt tattgacatg 780 aatgacaaca gacctgagtt cttacaccag gtttggaatg ggacagttcc tgagggatca 840 aagcctggaa catatgtgat gaccgtaaca gcaattgatg ctgacgatcc caatgccctc 900 aatgggatgt tgaggtacag aatcgtgtct caggctccaa gcaccccttc acccaacatg 960 tttacaatca acaatgagac tggtgacatc atcacagtgg cagctggact tgatcgagaa 1020 aaagtgcaac agtatacgtt aataattcaa gctacagaca tggaaggcaa tcccacatat 1080 ggcctttcaa acacagccac ggccgtcatc acagtgacag atgtcaatga caatcctcca 1140 gagtttactg ccatgacgtt ttatggtgaa gttcctgaga acagggtaga catcatagta 1200 gctaatctaa ctgtgaccga taaggatcaa ccccatacac cagcctggaa cgcagtgtac 1260 agaatcagtg gcggagatcc tactggacgg ttcgccatcc agaccgaccc aaacagcaac 1320 gacgggttag tcaccgtggt caaaccaatc gactttgaaa caaataggat gtttgtcctt 1380 actgttgctg cagaaaatca agtgccatta gccaagggaa ttcagcaccc ccctcagtca 1440 actgcaaccg tgtctgttac agttattgac gtaaatgaaa acccttattt tgcccccaat 1500 cctaagatca ttcgccaaga agaagggctt catgccggta ccatgttgac aacattcact 1560 gctcaggacc cagatcgata tatgcagcaa aatattagat acactaaatt atctgatcct 1620 gccaattggc taaaaataga tcctgtgaat ggacaaataa ctacaattgc tgttttggac 1680 cgagaatcac caaatgtgaa aaacaatata tataatgcta ctttccttgc ttctgacaat 1740 ggaattcctc ctatgagtgg aacaggaacg ctgcagatct atttacttga tattaatgac 1800 aatgcccctc aagtgttacc tcaagaggca gagacttgcg aaactccaga ccccaattca 1860 attaatatta cagcacttga ttatgacatt gatccaaatg ctggaccatt tgcttttgat 1920 cttcctttat ctccagtgac tattaagaga aattggacca tcactcggct taatggtgat 1980 tttgctcagc ttaatttaaa gataaaattt cttgaagctg gtatctatga agttcccatc 2040 ataatcacag attcgggtaa tcctcccaaa tcaaatattt ccatcctgcg tgtgaaggtt 2100 tgccagtgtg actccaacgg ggactgcaca gatgtggaca ggattgtggg tgcggggctt 2160 ggcaccggtg ccatcattgc catcctgctc tgcatcatca tcctgcttat ccttgtgctg 2220 atgtttgtgg tatggatgaa acgccgggat aaagaacgcc aggccaaaca acttttaatt 2280 gatccagaag atgatgtaag agataatatt ttaaaatatg atgaagaagg tggaggagaa 2340 gaagaccagg actatgactt gagccagctg cagcagcctg acactgtgga gcctgatgcc 2400 atcaagcctg tgggaatccg acgaatggat gaaagaccca tccacgccga gccccagtat 2460 ccggtccgat ctgcagcccc acaccctgga gacattgggg acttcattaa tgagggcctt 2520 aaagcggctg acaatgaccc cacagctcca ccatatgact ccctgttagt gtttgactat 2580 gaaggcagtg gctccactgc tgggtccttg agctccctta attcctcaag tagtggtggt 2640 gagcaggact atgattacct gaacgactgg gggccacggt tcaagaaact tgctgacatg 2700 tatggtggag gtgatgactg aacttcaggg tgaacttggt ttttggacaa gtacaaacaa 2760 tttcaactga tattcccaaa aagcattcag aagctaggct ttaactttgt agtctactag 2820 cacagtgctt gctggaggct ttggcatagg ctgcaaacca atttgggctc agagggaata 2880 tcagtgatcc atactgtttg gaaaaacact gagctcagtt acacttgaat tttacagtac 2940 agaagcactg ggattttatg tgcctttttg tacctttttc agattggaat tagttttctg 3000 tttaaggctt taatggtact gatttctgaa acgataagta aaagacaaaa tattttgtgg 3060 tgggagcagt aagttaaacc atgatatgct tcaacacgct tttgttacat tgcatttgct 3120 tttattaaaa tacaaaatta aacaaacaaa aaaactcatg gagcgatttt attatcttgg 3180 gggatgagac catgagattg gaaaatgtac attacttcta gttttagact ttagtttgtt 3240 tttttttttt tcactaaaat cttaaaactt actcagctgg ttgcaaataa agggagtttt 3300 catatcacca atttgtagca aaattgaatt ttttcataaa ctagaatgtt agacacattt 3360 tggtcttaat ccatgtacac ttttttattt ctgtattttt ccacttcact gtaaaaatag 3420 tatgtgtaca taatgtttta ttggcatagt ctatggagaa gtgcagaaac ttcagaacat 3480 gtgtatgtat tatttggact atggattcag gttttttgca tgtttatatc tttcgttatg 3540 gataaagtat ttacaaaaca gtgacatttg attcaattgt tgagctgtag ttagaatact 3600 caatttttaa tttttttaat ttttttattt tttattttct ttttggtttg gggagggaga 3660 aaagttctta gcacaaatgt tttacataat ttgtaccaaa aaaaaaaaaa aaggaaagga 3720 aagaaagggg tggcctgaca ctggtggcac tactaagtgt gtgttttttt aaaaaaaaaa 3780 tggaaaaaaa aaagctttta aactggagag acttctgaca acagctttgc ctctgtattg 3840 tgtaccagaa tataaatgat acacctctga ccccagcgtt ctgaataaaa tgctaatttt 3900 ggatctgg 3908 <![CDATA[<210> 130]]> <![CDATA[<211> 4016]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 130]]> gccgtttctc cgcgccgctg ttggtgctgc cgctgcctcc tcctcctccg ccgccgccgc 60 cgccgccgcc gcctcctccg gctcttcgct cggcccctct ccgcctccat gtgccggata 120 gcgggagcgc tgcggaccct gctgccgctg ctggcggccc tgcttcaggc gtctgtagag 180 gcttctggtg aaatcgcatt atgcaagact ggatttcctg aagatgttta cagtgcagtc 240 ttatcgaagg atgtgcatga aggacagcct cttctcaatg tgaagtttag caactgcaat 300 ggaaaaagaa aagtacaata tgagagcagt gagcctgcag attttaaggt ggatgaagat 360 ggcatggtgt atgccgtgag aagctttcca ctctcttctg agcatgccaa gttcctgata 420 tatgcccaag acaaagagac ccaggaaaag tggcaagtgg cagtaaaatt gagcctgaag 480 ccaaccttaa ctgaggagtc agtgaaggag tcagcagaag ttgaagaaat agtgttccca 540 agacaattca gtaagcacag tggccaccta caaaggcaga agagagactg ggtcatccct 600 ccaatcaact tgccagaaaa ctccagggga ccttttcctc aagagcttgt caggatcagg 660 tctgatagag ataaaaacct ttcactgcgg tacagtgtaa ctgggccagg agctgaccag 720 cctccaactg gtatcttcat tatcaacccc atctcgggtc agctgtcggt gacaaagccc 780 ctggatcgcg agcagatagc ccggtttcat ttgagggcac atgcagtaga tattaatgga 840 aatcaagtgg agaaccccat tgacattgtc atcaatgtta ttgacatgaa tgacaacaga 900 cctgagttct tacaccaggt ttggaatggg acagttcctg agggatcaaa gcctggaaca 960 tatgtgatga ccgtaacagc aattgatgct gacgatccca atgccctcaa tgggatgttg 1020 aggtacagaa tcgtgtctca ggctccaagc accccttcac ccaacatgtt tacaatcaac 1080 aatgagactg gtgacatcat cacagtggca gctggacttg atcgagaaaa agtgcaacag 1140 tatacgttaa taattcaagc tacagacatg gaaggcaatc ccacatatgg cctttcaaac 1200 acagccacgg ccgtcatcac agtgacagat gtcaatgaca atcctccaga gtttactgcc 1260 atgacgtttt atggtgaagt tcctgagaac agggtagaca tcatagtagc taatctaact 1320 gtgaccgata aggatcaacc ccatacacca gcctggaacg cagtgtacag aatcagtggc 1380 ggagatccta ctggacggtt cgccatccag accgacccaa acagcaacga cgggttagtc 1440 accgtggtca aaccaatcga ctttgaaaca aataggatgt ttgtccttac tgttgctgca 1500 gaaaatcaag tgccattagc caagggaatt cagcaccccc ctcagtcaac tgcaaccgtg 1560 tctgttacag ttattgacgt aaatgaaaac ccttattttg cccccaatcc taagatcatt 1620 cgccaagaag aagggcttca tgccggtacc atgttgacaa cattcactgc tcaggaccca 1680 gatcgatata tgcagcaaaa tattagatac actaaattat ctgatcctgc caattggcta 1740 aaaatagatc ctgtgaatgg acaaataact acaattgctg ttttggaccg agaatcacca 1800 aatgtgaaaa acaatatata taatgctact ttccttgctt ctgacaatgg aattcctcct 1860 atgagtggaa caggaacgct gcagatctat ttacttgata ttaatgacaa tgcccctcaa 1920 gtgttacctc aagaggcaga gacttgcgaa actccagacc ccaattcaat taatattaca 1980 gcacttgatt atgacattga tccaaatgct ggaccatttg cttttgatct tcctttatct 2040 ccagtgacta ttaagagaaa ttggaccatc actcggctta atggtgattt tgctcagctt 2100 aatttaaaga taaaatttct tgaagctggt atctatgaag ttcccatcat aatcacagat 2160 tcgggtaatc ctcccaaatc aaatatttcc atcctgcgtg tgaaggtttg ccagtgtgac 2220 tccaacgggg actgcacaga tgtggacagg attgtgggtg cggggcttgg caccggtgcc 2280 atcattgcca tcctgctctg catcatcatc ctgcttatcc ttgtgctgat gtttgtggta 2340 tggatgaaac gccgggataa agaacgccag gccaaacaac ttttaattga tccagaagat 2400 gatgtaagag ataatatttt aaaatatgat gaagaaggtg gaggagaaga agaccaggac 2460 tatgacttga gccagctgca gcagcctgac actgtggagc ctgatgccat caagcctgtg 2520 ggaatccgac gaatggatga aagacccatc cacgccgagc cccagtatcc ggtccgatct 2580 gcagccccac accctggaga cattggggac ttcattaatg agggccttaa agcggctgac 2640 aatgacccca cagctccacc atatgactcc ctgttagtgt ttgactatga aggcagtggc 2700 tccactgctg ggtccttgag ctcccttaat tcctcaagta gtggtggtga gcaggactat 2760 gattacctga acgactgggg gccacggttc aagaaacttg ctgacatgta tggtggaggt 2820 gatgactgaa cttcagggtg aacttggttt ttggacaagt acaaacaatt tcaactgata 2880 ttcccaaaaa gcattcagaa gctaggcttt aactttgtag tctactagca cagtgcttgc 2940 tggaggcttt ggcataggct gcaaaccaat ttgggctcag agggaatatc agtgatccat 3000 actgtttgga aaaacactga gctcagttac acttgaattt tacagtacag aagcactggg 3060 attttatgtg cctttttgta cctttttcag attggaatta gttttctgtt taaggcttta 3120 atggtactga tttctgaaac gataagtaaa agacaaaata ttttgtggtg ggagcagtaa 3180 gttaaaccat gatatgcttc aacacgcttt tgttacattg catttgcttt tattaaaata 3240 caaaattaaa caaacaaaaa aactcatgga gcgattttat tatcttgggg gatgagacca 3300 tgagattgga aaatgtacat tacttctagt tttagacttt agtttgtttt tttttttttc 3360 actaaaatct taaaacttac tcagctggtt gcaaataaag ggagttttca tatcaccaat 3420 ttgtagcaaa attgaatttt ttcataaact agaatgttag acacattttg gtcttaatcc 3480 atgtacactt ttttatttct gtatttttcc acttcactgt aaaaatagta tgtgtacata 3540 atgttttatt ggcatagtct atggagaagt gcagaaactt cagaacatgt gtatgtatta 3600 tttggactat ggattcaggt tttttgcatg tttatatctt tcgttatgga taaagtattt 3660 acaaaacagt gacatttgat tcaattgttg agctgtagtt agaatactca atttttaatt 3720 tttttaattt ttttattttt tattttcttt ttggtttggg gagggagaaa agttcttagc 3780 acaaatgttt tacataattt gtaccaaaaa aaaaaaaaaa ggaaaggaaa gaaaggggtg 3840 gcctgacact ggtggcacta ctaagtgtgt gtttttttaa aaaaaaaatg gaaaaaaaaa 3900 agcttttaaa ctggagagac ttctgacaac agctttgcct ctgtattgtg taccagaata 3960 taaatgatac acctctgacc ccagcgttct gaataaaatg ctaattttgg atctgg 4016 <![CDATA[<210> 131]]> <![CDATA[<211> 7716]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 131]]> ggcggcgcgc cgggcagcgc ttcggtggcg gcggcggccg cggtggcagc gaaggcggcg 60 gcggcggcgg cagtggcagt ggccgctgca gccccacact ccgccgccaa actggaggag 120 cgacggaagc cagaccccag gaggatggag gatgaagctg tcctggacag aggggcttcc 180 ttcctcaagc atgtgtgtga tgaagaagaa gtagaaggcc accataccat ttacatcgga 240 gtccatgtgc cgaagagtta caggagaagg agacgtcaca agagaaagac agggcacaaa 300 gaaaagaagg aaaaggagag aatctctgag aactactctg acaaatcaga tattgaaaat 360 gctgatgaat ccagcagcag catcctaaaa cctctcatct ctcctgctgc agaacgcatc 420 cgattcatct tgggagagga ggatgacagc ccagctcccc ctcagctctt cacggaactg 480 gatgagctgc tggccgtgga tgggcaggag atggagtgga aggaaacagc caggtggatc 540 aagtttgaag aaaaagtgga acagggtggg gaaagatgga gcaagcccca tgtggccaca 600 ttgtcccttc atagtttatt tgagctgagg acatgtatgg agaaaggatc catcatgctt 660 gatcgggagg cttcttctct cccacagttg gtggagatga ttgttgacca tcagattgag 720 acaggcctat tgaaacctga acttaaggat aaggtgacct atactttgct ccggaagcac 780 cggcatcaaa ccaagaaatc caaccttcgg tccctggctg acattgggaa gacagtctcc 840 agtgcaagta ggatgtttac caaccctgat aatggtagcc cagccatgac ccataggaat 900 ctgacttcct ccagtctgaa tgacatttct gataaaccgg agaaggacca gctgaagaat 960 aagttcatga aaaaattgcc acgtgatgca gaagcttcca acgtgcttgt tggggaggtt 1020 gactttttgg atactccttt cattgccttt gttaggctac agcaggctgt catgctgggt 1080 gccctgactg aagttcctgt gcccacaagg ttcttgttca ttctcttagg tcctaagggg 1140 aaagccaagt cctaccacga gattggcaga gccattgcca ccctgatgtc tgatgaggtg 1200 ttccatgaca ttgcttataa agcaaaagac aggcacgacc tgattgctgg tattgatgag 1260 ttcctagatg aagtcatcgt ccttccacct ggggaatggg atccagcaat taggatagag 1320 cctcctaaga gtcttccatc ctctgacaaa agaaagaata tgtactcagg tggagagaat 1380 gttcagatga atggggatac gccccatgat ggaggtcacg gaggaggagg acatggggat 1440 tgtgaagaat tgcagcgaac tggacggttc tgtggtggac taattaaaga cataaagagg 1500 aaagcgccat tttttgccag tgatttttat gatgctttaa atattcaagc tctttcggca 1560 attctcttca tttatctggc aactgtaact aatgctatca cttttggagg actgcttggg 1620 gatgccactg acaacatgca gggcgtgttg gagagtttcc tgggcactgc tgtctctgga 1680 gccatctttt gcctttttgc tggtcaacca ctcactattc tgagcagcac cggacctgtc 1740 ctagtttttg agaggcttct atttaatttc agcaaggaca ataattttga ctatttggag 1800 tttcgccttt ggattggcct gtggtccgcc ttcctatgtc tcattttggt agccactgat 1860 gccagcttct tggttcaata cttcacacgt ttcacggagg agggcttttc ctctctgatt 1920 agcttcatct ttatctatga tgctttcaag aagatgatca agcttgcaga ttactacccc 1980 atcaactcca acttcaaagt gggctacaac actctctttt cctgtacctg tgtgccacct 2040 gacccagcta atatctcaat atctaatgac accacactgg ccccagagta tttgccaact 2100 atgtcttcta ctgacatgta ccataatact acctttgact gggcattttt gtcgaagaag 2160 gagtgttcaa aatacggagg aaacctcgtc gggaacaact gtaattttgt tcctgatatc 2220 acactcatgt cttttatcct cttcttggga acctacacct cttccatggc tctgaaaaaa 2280 ttcaaaacta gtccttattt tccaaccaca gcaagaaaac tgatcagtga ttttgccatt 2340 atcttgtcca ttctcatctt ttgtgtaata gatgccctag taggcgtgga caccccaaaa 2400 ctaattgtgc caagtgagtt caagccaaca agtccaaacc gaggttggtt cgttccaccg 2460 tttggagaaa acccctggtg ggtgtgcctt gctgctgcta tcccggcttt gttggtcact 2520 atactgattt tcatggacca acaaattaca gctgtgattg taaacaggaa agaacataaa 2580 ctcaagaaag gagcagggta tcacttggat ctcttttggg tggccatcct catggttata 2640 tgctccctca tggctcttcc gtggtatgta gctgctacgg tcatctccat tgctcacatc 2700 gacagtttga agatggagac agagacttct gcacctggag aacaaccaaa gtttctagga 2760 gtgagggaac aaagagtcac tggaaccctt gtgtttattc tgactggtct gtcagtcttt 2820 atggctccca tcttgaagtt tatacccatg cctgtactct atggtgtgtt cctgtatatg 2880 ggagtagcat cccttaatgg tgtgcagttc atggatcgtc tgaagctgct tctgatgcct 2940 ctgaagcatc agcctgactt catctacctg cgtcatgttc ctctgcgcag agtccacctg 3000 ttcactttcc tgcaggtgtt gtgtctggcc ctgctttgga tcctcaagtc aacggtggct 3060 gctatcattt ttccagtaat gatcttggca cttgtagctg tcagaaaagg catggactac 3120 ctcttctccc agcacgacct cagcttcctg gatgatgtca ttccagaaaa ggacaagaaa 3180 aagaaggagg atgagaagaa aaagaaaaag aagaagggaa gtctggacag tgacaatgat 3240 gattctgact gcccatactc agaaaaagtt ccaagtatta aaattccaat ggacatcatg 3300 gaacagcaac ctttcctaag cgatagcaaa ccttctgaca gagaaagatc accaacattc 3360 cttgaacgcc acacatcatg ctgataaaat tcctttcctt cagtcactcg gtatgccaag 3420 tcctcctaga actccagtaa aagttgtgcc tcaaattaga atagaacttg aacctgaaga 3480 caatgattat ttctggagga gcaagggaac agaaactaca ttgtaacctg tttgtctttc 3540 ttaaaactga catttgttgt taatgtcatt tgtttttgtt tggctgtttg tttatttttt 3600 aacttttatt tcgtctcagt ttttggtcac aggccaaata atacagcgct ctctctgctt 3660 ctctcttgca tagacacaat caagacaata gtgcaccgtt ccttaaaaac agcatctgag 3720 gaatccccct tttgttctta aactttcaga tgtgtccttt gataaccaaa ttctgtcact 3780 caagacacag acacgcacag accctgtcct ttgcctctat taagcagagg atggaagtat 3840 taaggatttt gtaacacctt ttatgaaaat gttgaaggaa cttaaaactt tagctttgga 3900 gctgtgctta ctggcttgtc tttgtctggt agaacaaacc ttgacctcca gacagagtcc 3960 cttctcactt atagagctct ccaggactgg aaaaagtgct gctattttaa cttgctcttg 4020 cttgtaaatc ctaatcttag agttatcaaa agaagaaaaa actgaaggta ctttactccc 4080 tatagagaaa ccattgccat cattgtagca agtgctggaa tgtccctttt ttcctatgca 4140 acttttttta accctttaat gaacttatct gttgagtaca ttgaagaata tttttcttcc 4200 tagattttgt tgtttaaatt atggggccta acctgccact tattttttgt caatttttaa 4260 aacttttttt taattactgt aaagaaaatg aattttttcc tgcagcagga aacatagttt 4320 tgagtagttc tacctcttat ttgtagctgc caggctttct gtaaaaattg tattgtatat 4380 aatgtgattt ttacacatac atacacacac aaatacacaa tctctagggt aagccagaag 4440 gcaagatcag attaaaaaca ccatgtttct aagcatccat ttttcccttt ctttaaaaga 4500 aacttaactg ttctatgaag gagattgagg gagaagagac aaactcctat gtcatgagaa 4560 taaccgatgt tctgataata gtagcatcta ggtacagatg ctggttgtat taccacgtca 4620 atgtcctatg cagtattgtt agacattttc tcattttgaa atatttgtgt gtttgtgtat 4680 gtgctctgtg ccatggctgg tgtatatatg tgcaatgtta gaaggcaaaa gagtgatggt 4740 aggcagaggg caaagtcatt gaatctctta tgccagtttt cataaaaccc aaaccacata 4800 tgaaaaaatc cattaagggt ccaagaagtc tgtccatatg aaaatgaggg taaatatagt 4860 ttatttccca ggtatcagtc attataattg atataatagc tctaacatgc aatataaaat 4920 tcataggagt attaatagcc catttacaca tctataaaat gtaatgggat tgcagagctg 4980 cagagtacag tgtaacagta ctctcatgca atttttttca ggatgcaaag gcaattattc 5040 tttgtaagcg ggacatttag aatatatttg tgtacatatt atatgtatgt atatttcaaa 5100 gtaccacact gaaaattaga catttattaa ccaaatttaa cgtggtattt aaaggtaata 5160 tttttaatat gatacattac atattgtgaa tgtatactaa aaaaacattt taaatgttaa 5220 aattataatt tcagattcat ataaccacaa ctgtgatata tcctaactat aaccagttgt 5280 tgaggggtat actagaagca gaatgaaacc acattttttg gtttgataat atgcacttat 5340 tgactcccac tcattgttat gttaattaag ttattattct gtctccttgt aattttgatt 5400 acaaaaattt tattatcctg agttagctgt tacttttaca gtacctgata ctcctaaaac 5460 ttttaactta tacaaattag tcaataatga ccccaatttt ttcattaaaa taatagtggt 5520 gaattatatg ttattgtgtt aaaacctcac ttgccaaatt ctggcttcac atttgtattt 5580 agggctatcc ttaaaatgat gagtctatat tatctagctt tctattaccc taatataaac 5640 tggtataaga agactttcct tttttcttta tgcatggaag catcaataaa ttgtttaaaa 5700 accatgtata gtaaattcag cttaacccgt gatcttctta agttaaaggt acttttgttt 5760 tataaaagct ctagataaaa ctttcttttc tgatcatgaa tcaagtatct gtggtttcat 5820 gcccctctct atacctttca aagaactcct gaagcaactt aactcatcat ttcagcctct 5880 gagtagaggt aaaacctatg tgtacttctg tttatgatcc atattgatat ttatgacatg 5940 aacacagaat agtaccttac atttgctaaa cagacagtta atatcaaatc ctttcaatat 6000 tctgggaacc cagggaagtt tttaaaaatg tcattacttt caaaggaaca gaagtagtta 6060 accaaactaa caagcaaaac ctgaggttta cctagtgaca ccaaattatc ggtattttaa 6120 ctgaatttac ccattgacta agaatgaacc agatttggtg gtggttttgt ttctatgcaa 6180 actggacaca aattacaaca gtaaattttt ttataagtgc ttctcccttc tccatgatgt 6240 gacttccgga gataaaggat tcaaaagata aagacaaagt acgctcagag ttgttaacca 6300 gaaagtcctg gctgtggttg cagaaacact gttggaagaa aagagatgac taagtcaagt 6360 gtctgcctta tcaaaagagc aaaaatgcct ctggttttgt gtttgggaga aaagtatctt 6420 ggacgcactg ttttccttga taaaagtcat cttctctact gtgtgaaatg aatacttgga 6480 attctaattg ttttgtgtgc caggggcagt aatgtccctg cctcttctcc caatcaaggt 6540 tgaggagtgg ggctggggag aggacttaac tgacttaaga agtaggaaaa caaaaacctc 6600 tctcctcagc cttccacctc caagagagga ggaaaaacag ttgtctgctg tctgtaattc 6660 agtttgcgtg tattttatgc tcatgcacca acccatacag agtaaatctt ttatcaactg 6720 tatactggtg tttaatagag aatgattgtc ttccgagttt tttggttcct tttttaactg 6780 tgttaaagta cttgaaatgt attgactgct gactatattt taaaaacaaa atgaaataat 6840 ttgagttgta ttacagaggt tgacattgtt cagggatggg acaaagcctt cttcaatcct 6900 tttcatacta cttaatgatt ttggtgcagg aacctgagat tttctgattt atatttcatg 6960 atatttcaca tttgctcttc acagcatgag catgaagccc agtggcacca aatggctggg 7020 tacaatcaag tgatattttg tagcacctca ctatctgaaa ggccatgagt tttcagatga 7080 tttcattgag cttcattgca gcctgaaatt ttaaaaaagt tgtgtaatac gccaaccagt 7140 caagttgtgt tttggccaga gatttagata tgtccaattt cctggctcat ttcattgtgc 7200 tctatgggta cgtataaaaa gcaagaattc tgtttcctag gcaaacattg caactcaggg 7260 ctaaagtcat ccagtgaaac ttttagagcc agaagtaact ttgtcccagt cctacaatgt 7320 gaaaagagtg aatagttgcc tctttttagc cattttcatg gctggtacat attcgtacgc 7380 attacttttc agaatcaata cgcactttca gatattctta tttttattct cttaagtctt 7440 tattaacttt ggagagagaa atgatgcatc tttttatttt aaatgaagta gatcaacatg 7500 gtggaacaaa atgataaaga acagaaaaca tttcaatata ttactaataa ctttttccaa 7560 tataaatcct aaaattccta taacatagta ttttacagtt ttatgaagct ttctattgtg 7620 acttttatgg aattaagaga tgaagaagat gagatatttt agcatttata tttttcaaaa 7680 ttatatgtat acttaaaaat aaagtaactt tatgca 7716 <![CDATA[<210> 132]]> <![CDATA[<211> 8113]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 132]]> ggcacagcct ccgccgcggc cgccttccgt gagcccccgc accccggctt gctcccgagg 60 ggcgcctggg ctgggctcca ctgctgcagt gttagttact agcaggaaca tcagagatcc 120 ccataaatat gcaggagctg caggaggcaa agtagagtag acgcccgcgc tcttacacac 180 tcgctcgccg cgcaccacac aggctgtgta gacatccccc cgcgccacct ttcccctttc 240 ctcgcgggcc gttcaggttg cagtcctgcc tgctccgaag accctcccgc cccagcgcct 300 ttgccccgct ctcccgcgct cgcctctctc cggagcgcgc acccacccag gcggcaaagt 360 tgtgactact tgggcgcggg tgactggcgc cccgctcgct ccgcgcccgg cgcagacaac 420 ttcccgcggc tcggccccgc cgcgtcccgg gctcgcgcct ccagggattc cgcggccccc 480 cagcctccaa ccccggcggc gcgccgggca gcgcttcggt ggcggcggcg gccgcggtgg 540 cagcgaaggc ggcggcggcg gcggcagtgg cagtggccgc tgcagcccca cactccgccg 600 ccaaactgga ggagcgacgg aagccagacc ccaggaggat ggaggatgaa gctgtcctgg 660 acagaggggc ttccttcctc aagcatgtgt gtgatgaaga agaagtagaa ggccaccata 720 ccatttacat cggagtccat gtgccgaaga gttacaggag aaggagacgt cacaagagaa 780 agacagggca caaagaaaag aaggaaaagg agagaatctc tgagaactac tctgacaaat 840 cagatattga aaatgctgat gaatccagca gcagcatcct aaaacctctc atctctcctg 900 ctgcagaacg catccgattc atcttgggag aggaggatga cagcccagct ccccctcagc 960 tcttcacgga actggatgag ctgctggccg tggatgggca ggagatggag tggaaggaaa 1020 cagccaggtg gatcaagttt gaagaaaaag tggaacaggg tggggaaaga tggagcaagc 1080 cccatgtggc cacattgtcc cttcatagtt tatttgagct gaggacatgt atggagaaag 1140 gatccatcat gcttgatcgg gaggcttctt ctctcccaca gttggtggag atgattgttg 1200 accatcagat tgagacaggc ctattgaaac ctgaacttaa ggataaggtg acctatactt 1260 tgctccggaa gcaccggcat caaaccaaga aatccaacct tcggtccctg gctgacattg 1320 ggaagacagt ctccagtgca agtaggatgt ttaccaaccc tgataatggt agcccagcca 1380 tgacccatag gaatctgact tcctccagtc tgaatgacat ttctgataaa ccggagaagg 1440 accagctgaa gaataagttc atgaaaaaat tgccacgtga tgcagaagct tccaacgtgc 1500 ttgttgggga ggttgacttt ttggatactc ctttcattgc ctttgttagg ctacagcagg 1560 ctgtcatgct gggtgccctg actgaagttc ctgtgcccac aaggttcttg ttcattctct 1620 taggtcctaa ggggaaagcc aagtcctacc acgagattgg cagagccatt gccaccctga 1680 tgtctgatga ggtgttccat gacattgctt ataaagcaaa agacaggcac gacctgattg 1740 ctggtattga tgagttccta gatgaagtca tcgtccttcc acctggggaa tgggatccag 1800 caattaggat agagcctcct aagagtcttc catcctctga caaaagaaag aatatgtact 1860 caggtggaga gaatgttcag atgaatgggg atacgcccca tgatggaggt cacggaggag 1920 gaggacatgg ggattgtgaa gaattgcagc gaactggacg gttctgtggt ggactaatta 1980 aagacataaa gaggaaagcg ccattttttg ccagtgattt ttatgatgct ttaaatattc 2040 aagctctttc ggcaattctc ttcatttatc tggcaactgt aactaatgct atcacttttg 2100 gaggactgct tggggatgcc actgacaaca tgcagggcgt gttggagagt ttcctgggca 2160 ctgctgtctc tggagccatc ttttgccttt ttgctggtca accactcact attctgagca 2220 gcaccggacc tgtcctagtt tttgagaggc ttctatttaa tttcagcaag gacaataatt 2280 ttgactattt ggagtttcgc ctttggattg gcctgtggtc cgccttccta tgtctcattt 2340 tggtagccac tgatgccagc ttcttggttc aatacttcac acgtttcacg gaggagggct 2400 tttcctctct gattagcttc atctttatct atgatgcttt caagaagatg atcaagcttg 2460 cagattacta ccccatcaac tccaacttca aagtgggcta caacactctc ttttcctgta 2520 cctgtgtgcc acctgaccca gctaatatct caatatctaa tgacaccaca ctggccccag 2580 agtatttgcc aactatgtct tctactgaca tgtaccataa tactaccttt gactgggcat 2640 ttttgtcgaa gaaggagtgt tcaaaatacg gaggaaacct cgtcgggaac aactgtaatt 2700 ttgttcctga tatcacactc atgtctttta tcctcttctt gggaacctac acctcttcca 2760 tggctctgaa aaaattcaaa actagtcctt attttccaac cacagcaaga aaactgatca 2820 gtgattttgc cattatcttg tccattctca tcttttgtgt aatagatgcc ctagtaggcg 2880 tggacacccc aaaactaatt gtgccaagtg agttcaagcc aacaagtcca aaccgaggtt 2940 ggttcgttcc accgtttgga gaaaacccct ggtgggtgtg ccttgctgct gctatcccgg 3000 ctttgttggt cactatactg attttcatgg accaacaaat tacagctgtg attgtaaaca 3060 ggaaagaaca taaactcaag aaaggagcag ggtatcactt ggatctcttt tgggtggcca 3120 tcctcatggt tatatgctcc ctcatggctc ttccgtggta tgtagctgct acggtcatct 3180 ccattgctca catcgacagt ttgaagatgg agacagagac ttctgcacct ggagaacaac 3240 caaagtttct aggagtgagg gaacaaagag tcactggaac ccttgtgttt attctgactg 3300 gtctgtcagt ctttatggct cccatcttga agtttatacc catgcctgta ctctatggtg 3360 tgttcctgta tatgggagta gcatccctta atggtgtgca gttcatggat cgtctgaagc 3420 tgcttctgat gcctctgaag catcagcctg acttcatcta cctgcgtcat gttcctctgc 3480 gcagagtcca cctgttcact ttcctgcagg tgttgtgtct ggccctgctt tggatcctca 3540 agtcaacggt ggctgctatc atttttccag taatgatctt ggcacttgta gctgtcagaa 3600 aaggcatgga ctacctcttc tcccagcacg acctcagctt cctggatgat gtcattccag 3660 aaaaggacaa gaaaaagaag gaggatgaga agaaaaagaa aaagaagaag ggaagtctgg 3720 acagtgacaa tgatgatgag aaagatcacc aacattcctt gaacgccaca catcatgctg 3780 ataaaattcc tttccttcag tcactcggta tgccaagtcc tcctagaact ccagtaaaag 3840 ttgtgcctca aattagaata gaacttgaac ctgaagacaa tgattatttc tggaggagca 3900 agggaacaga aactacattg taacctgttt gtctttctta aaactgacat ttgttgttaa 3960 tgtcatttgt ttttgtttgg ctgtttgttt attttttaac ttttatttcg tctcagtttt 4020 tggtcacagg ccaaataata cagcgctctc tctgcttctc tcttgcatag acacaatcaa 4080 gacaatagtg caccgttcct taaaaacagc atctgaggaa tccccctttt gttcttaaac 4140 tttcagatgt gtcctttgat aaccaaattc tgtcactcaa gacacagaca cgcacagacc 4200 ctgtcctttg cctctattaa gcagaggatg gaagtattaa ggattttgta acacctttta 4260 tgaaaatgtt gaaggaactt aaaactttag ctttggagct gtgcttactg gcttgtcttt 4320 gtctggtaga acaaaccttg acctccagac agagtccctt ctcacttata gagctctcca 4380 ggactggaaa aagtgctgct attttaactt gctcttgctt gtaaatccta atcttagagt 4440 tatcaaaaga agaaaaaact gaaggtactt tactccctat agagaaacca ttgccatcat 4500 tgtagcaagt gctggaatgt cccttttttc ctatgcaact ttttttaacc ctttaatgaa 4560 cttatctgtt gagtacattg aagaatattt ttcttcctag attttgttgt ttaaattatg 4620 gggcctaacc tgccacttat tttttgtcaa tttttaaaac ttttttttaa ttactgtaaa 4680 gaaaatgaat tttttcctgc agcaggaaac atagttttga gtagttctac ctcttatttg 4740 tagctgccag gctttctgta aaaattgtat tgtatataat gtgattttta cacatacata 4800 cacacacaaa tacacaatct ctagggtaag ccagaaggca agatcagatt aaaaacacca 4860 tgtttctaag catccatttt tccctttctt taaaagaaac ttaactgttc tatgaaggag 4920 attgagggag aagagacaaa ctcctatgtc atgagaataa ccgatgttct gataatagta 4980 gcatctaggt acagatgctg gttgtattac cacgtcaatg tcctatgcag tattgttaga 5040 cattttctca ttttgaaata tttgtgtgtt tgtgtatgtg ctctgtgcca tggctggtgt 5100 atatatgtgc aatgttagaa ggcaaaagag tgatggtagg cagagggcaa agtcattgaa 5160 tctcttatgc cagttttcat aaaacccaaa ccacatatga aaaaatccat taagggtcca 5220 agaagtctgt ccatatgaaa atgagggtaa atatagttta tttcccaggt atcagtcatt 5280 ataattgata taatagctct aacatgcaat ataaaattca taggagtatt aatagcccat 5340 ttacacatct ataaaatgta atgggattgc agagctgcag agtacagtgt aacagtactc 5400 tcatgcaatt tttttcagga tgcaaaggca attattcttt gtaagcggga catttagaat 5460 atatttgtgt acatattata tgtatgtata tttcaaagta ccacactgaa aattagacat 5520 ttattaacca aatttaacgt ggtatttaaa ggtaatattt ttaatatgat acattacata 5580 ttgtgaatgt atactaaaaa aacattttaa atgttaaaat tataatttca gattcatata 5640 accacaactg tgatatatcc taactataac cagttgttga ggggtatact agaagcagaa 5700 tgaaaccaca ttttttggtt tgataatatg cacttattga ctcccactca ttgttatgtt 5760 aattaagtta ttattctgtc tccttgtaat tttgattaca aaaattttat tatcctgagt 5820 tagctgttac ttttacagta cctgatactc ctaaaacttt taacttatac aaattagtca 5880 ataatgaccc caattttttc attaaaataa tagtggtgaa ttatatgtta ttgtgttaaa 5940 acctcacttg ccaaattctg gcttcacatt tgtatttagg gctatcctta aaatgatgag 6000 tctatattat ctagctttct attaccctaa tataaactgg tataagaaga ctttcctttt 6060 ttctttatgc atggaagcat caataaattg tttaaaaacc atgtatagta aattcagctt 6120 aacccgtgat cttcttaagt taaaggtact tttgttttat aaaagctcta gataaaactt 6180 tcttttctga tcatgaatca agtatctgtg gtttcatgcc cctctctata cctttcaaag 6240 aactcctgaa gcaacttaac tcatcatttc agcctctgag tagaggtaaa acctatgtgt 6300 acttctgttt atgatccata ttgatattta tgacatgaac acagaatagt accttacatt 6360 tgctaaacag acagttaata tcaaatcctt tcaatattct gggaacccag ggaagttttt 6420 aaaaatgtca ttactttcaa aggaacagaa gtagttaacc aaactaacaa gcaaaacctg 6480 aggtttacct agtgacacca aattatcggt attttaactg aatttaccca ttgactaaga 6540 atgaaccaga tttggtggtg gttttgtttc tatgcaaact ggacacaaat tacaacagta 6600 aattttttta taagtgcttc tcccttctcc atgatgtgac ttccggagat aaaggattca 6660 aaagataaag acaaagtacg ctcagagttg ttaaccagaa agtcctggct gtggttgcag 6720 aaacactgtt ggaagaaaag agatgactaa gtcaagtgtc tgccttatca aaagagcaaa 6780 aatgcctctg gttttgtgtt tgggagaaaa gtatcttgga cgcactgttt tccttgataa 6840 aagtcatctt ctctactgtg tgaaatgaat acttggaatt ctaattgttt tgtgtgccag 6900 gggcagtaat gtccctgcct cttctcccaa tcaaggttga ggagtggggc tggggagagg 6960 acttaactga cttaagaagt aggaaaacaa aaacctctct cctcagcctt ccacctccaa 7020 gagaggagga aaaacagttg tctgctgtct gtaattcagt ttgcgtgtat tttatgctca 7080 tgcaccaacc catacagagt aaatctttta tcaactgtat actggtgttt aatagagaat 7140 gattgtcttc cgagtttttt ggttcctttt ttaactgtgt taaagtactt gaaatgtatt 7200 gactgctgac tatattttaa aaacaaaatg aaataatttg agttgtatta cagaggttga 7260 cattgttcag ggatgggaca aagccttctt caatcctttt catactactt aatgattttg 7320 gtgcaggaac ctgagatttt ctgatttata tttcatgata tttcacattt gctcttcaca 7380 gcatgagcat gaagcccagt ggcaccaaat ggctgggtac aatcaagtga tattttgtag 7440 cacctcacta tctgaaaggc catgagtttt cagatgattt cattgagctt cattgcagcc 7500 tgaaatttta aaaaagttgt gtaatacgcc aaccagtcaa gttgtgtttt ggccagagat 7560 ttagatatgt ccaatttcct ggctcatttc attgtgctct atgggtacgt ataaaaagca 7620 agaattctgt ttcctaggca aacattgcaa ctcagggcta aagtcatcca gtgaaacttt 7680 tagagccaga agtaactttg tcccagtcct acaatgtgaa aagagtgaat agttgcctct 7740 ttttagccat tttcatggct ggtacatatt cgtacgcatt acttttcaga atcaatacgc 7800 actttcagat attcttattt ttattctctt aagtctttat taactttgga gagagaaatg 7860 atgcatcttt ttattttaaa tgaagtagat caacatggtg gaacaaaatg ataaagaaca 7920 gaaaacattt caatatatta ctaataactt tttccaatat aaatcctaaa attcctataa 7980 catagtattt tacagtttta tgaagctttc tattgtgact tttatggaat taagagatga 8040 agaagatgag atattttagc atttatattt ttcaaaatta tatgtatact taaaaataaa 8100 gtaactttat gca 8113 <![CDATA[<210> 133]]> <![CDATA[<211> 7669]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 133]]> gtcttataat tttggatgag tcataagtgg agaaggaggg gaagtgagtg gttagacctc 60 agctcatctg agggctaaag gttctttgtg acacatcaca cagaattgga gtgctgtcct 120 tctggagagt ggtggagaac caagatacag ttcagaacca aaggaataga gaagggcttt 180 gatttctttt tggctttaga ttggggattt gggaggctta gcaggaaaga tgtccactga 240 aaatgtggaa gggaagccca gtaaccttgg ggagagagga agagcccgga gctccacttt 300 cctcagggtt gtccagccaa tgtttaacca cagtattttc acttctgcag tctctcctgc 360 tgcagaacgc atccgattca tcttgggaga ggaggatgac agcccagctc cccctcagct 420 cttcacggaa ctggatgagc tgctggccgt ggatgggcag gagatggagt ggaaggaaac 480 agccaggtgg atcaagtttg aagaaaaagt ggaacagggt ggggaaagat ggagcaagcc 540 ccatgtggcc acattgtccc ttcatagttt atttgagctg aggacatgta tggagaaagg 600 atccatcatg cttgatcggg aggcttcttc tctcccacag ttggtggaga tgattgttga 660 ccatcagatt gagacaggcc tattgaaacc tgaacttaag gataaggtga cctatacttt 720 gctccggaag caccggcatc aaaccaagaa atccaacctt cggtccctgg ctgacattgg 780 gaagacagtc tccagtgcaa gtaggatgtt taccaaccct gataatggta gcccagccat 840 gacccatagg aatctgactt cctccagtct gaatgacatt tctgataaac cggagaagga 900 ccagctgaag aataagttca tgaaaaaatt gccacgtgat gcagaagctt ccaacgtgct 960 tgttggggag gttgactttt tggatactcc tttcattgcc tttgttaggc tacagcaggc 1020 tgtcatgctg ggtgccctga ctgaagttcc tgtgcccaca aggttcttgt tcattctctt 1080 aggtcctaag gggaaagcca agtcctacca cgagattggc agagccattg ccaccctgat 1140 gtctgatgag gtgttccatg acattgctta taaagcaaaa gacaggcacg acctgattgc 1200 tggtattgat gagttcctag atgaagtcat cgtccttcca cctggggaat gggatccagc 1260 aattaggata gagcctccta agagtcttcc atcctctgac aaaagaaaga atatgtactc 1320 aggtggagag aatgttcaga tgaatgggga tacgccccat gatggaggtc acggaggagg 1380 aggacatggg gattgtgaag aattgcagcg aactggacgg ttctgtggtg gactaattaa 1440 agacataaag aggaaagcgc cattttttgc cagtgatttt tatgatgctt taaatattca 1500 agctctttcg gcaattctct tcatttatct ggcaactgta actaatgcta tcacttttgg 1560 aggactgctt ggggatgcca ctgacaacat gcagggcgtg ttggagagtt tcctgggcac 1620 tgctgtctct ggagccatct tttgcctttt tgctggtcaa ccactcacta ttctgagcag 1680 caccggacct gtcctagttt ttgagaggct tctatttaat ttcagcaagg acaataattt 1740 tgactatttg gagtttcgcc tttggattgg cctgtggtcc gccttcctat gtctcatttt 1800 ggtagccact gatgccagct tcttggttca atacttcaca cgtttcacgg aggagggctt 1860 ttcctctctg attagcttca tctttatcta tgatgctttc aagaagatga tcaagcttgc 1920 agattactac cccatcaact ccaacttcaa agtgggctac aacactctct tttcctgtac 1980 ctgtgtgcca cctgacccag ctaatatctc aatatctaat gacaccacac tggccccaga 2040 gtatttgcca actatgtctt ctactgacat gtaccataat actacctttg actgggcatt 2100 tttgtcgaag aaggagtgtt caaaatacgg aggaaacctc gtcgggaaca actgtaattt 2160 tgttcctgat atcacactca tgtcttttat cctcttcttg ggaacctaca cctcttccat 2220 ggctctgaaa aaattcaaaa ctagtcctta ttttccaacc acagcaagaa aactgatcag 2280 tgattttgcc attatcttgt ccattctcat cttttgtgta atagatgccc tagtaggcgt 2340 ggacacccca aaactaattg tgccaagtga gttcaagcca acaagtccaa accgaggttg 2400 gttcgttcca ccgtttggag aaaacccctg gtgggtgtgc cttgctgctg ctatcccggc 2460 tttgttggtc actatactga ttttcatgga ccaacaaatt acagctgtga ttgtaaacag 2520 gaaagaacat aaactcaaga aaggagcagg gtatcacttg gatctctttt gggtggccat 2580 cctcatggtt atatgctccc tcatggctct tccgtggtat gtagctgcta cggtcatctc 2640 cattgctcac atcgacagtt tgaagatgga gacagagact tctgcacctg gagaacaacc 2700 aaagtttcta ggagtgaggg aacaaagagt cactggaacc cttgtgttta ttctgactgg 2760 tctgtcagtc tttatggctc ccatcttgaa gtttataccc atgcctgtac tctatggtgt 2820 gttcctgtat atgggagtag catcccttaa tggtgtgcag ttcatggatc gtctgaagct 2880 gcttctgatg cctctgaagc atcagcctga cttcatctac ctgcgtcatg ttcctctgcg 2940 cagagtccac ctgttcactt tcctgcaggt gttgtgtctg gccctgcttt ggatcctcaa 3000 gtcaacggtg gctgctatca tttttccagt aatgatcttg gcacttgtag ctgtcagaaa 3060 aggcatggac tacctcttct cccagcacga cctcagcttc ctggatgatg tcattccaga 3120 aaaggacaag aaaaagaagg aggatgagaa gaaaaagaaa aagaagaagg gaagtctgga 3180 cagtgacaat gatgattctg actgcccata ctcagaaaaa gttccaagta ttaaaattcc 3240 aatggacatc atggaacagc aacctttcct aagcgatagc aaaccttctg acagagaaag 3300 atcaccaaca ttccttgaac gccacacatc atgctgataa aattcctttc cttcagtcac 3360 tcggtatgcc aagtcctcct agaactccag taaaagttgt gcctcaaatt agaatagaac 3420 ttgaacctga agacaatgat tatttctgga ggagcaaggg aacagaaact acattgtaac 3480 ctgtttgtct ttcttaaaac tgacatttgt tgttaatgtc atttgttttt gtttggctgt 3540 ttgtttattt tttaactttt atttcgtctc agtttttggt cacaggccaa ataatacagc 3600 gctctctctg cttctctctt gcatagacac aatcaagaca atagtgcacc gttccttaaa 3660 aacagcatct gaggaatccc ccttttgttc ttaaactttc agatgtgtcc tttgataacc 3720 aaattctgtc actcaagaca cagacacgca cagaccctgt cctttgcctc tattaagcag 3780 aggatggaag tattaaggat tttgtaacac cttttatgaa aatgttgaag gaacttaaaa 3840 ctttagcttt ggagctgtgc ttactggctt gtctttgtct ggtagaacaa accttgacct 3900 ccagacagag tcccttctca cttatagagc tctccaggac tggaaaaagt gctgctattt 3960 taacttgctc ttgcttgtaa atcctaatct tagagttatc aaaagaagaa aaaactgaag 4020 gtactttact ccctatagag aaaccattgc catcattgta gcaagtgctg gaatgtccct 4080 tttttcctat gcaacttttt ttaacccttt aatgaactta tctgttgagt acattgaaga 4140 atatttttct tcctagattt tgttgtttaa attatggggc ctaacctgcc acttattttt 4200 tgtcaatttt taaaactttt ttttaattac tgtaaagaaa atgaattttt tcctgcagca 4260 ggaaacatag ttttgagtag ttctacctct tatttgtagc tgccaggctt tctgtaaaaa 4320 ttgtattgta tataatgtga tttttacaca tacatacaca cacaaataca caatctctag 4380 ggtaagccag aaggcaagat cagattaaaa acaccatgtt tctaagcatc catttttccc 4440 tttctttaaa agaaacttaa ctgttctatg aaggagattg agggagaaga gacaaactcc 4500 tatgtcatga gaataaccga tgttctgata atagtagcat ctaggtacag atgctggttg 4560 tattaccacg tcaatgtcct atgcagtatt gttagacatt ttctcatttt gaaatatttg 4620 tgtgtttgtg tatgtgctct gtgccatggc tggtgtatat atgtgcaatg ttagaaggca 4680 aaagagtgat ggtaggcaga gggcaaagtc attgaatctc ttatgccagt tttcataaaa 4740 cccaaaccac atatgaaaaa atccattaag ggtccaagaa gtctgtccat atgaaaatga 4800 gggtaaatat agtttatttc ccaggtatca gtcattataa ttgatataat agctctaaca 4860 tgcaatataa aattcatagg agtattaata gcccatttac acatctataa aatgtaatgg 4920 gattgcagag ctgcagagta cagtgtaaca gtactctcat gcaatttttt tcaggatgca 4980 aaggcaatta ttctttgtaa gcgggacatt tagaatatat ttgtgtacat attatatgta 5040 tgtatatttc aaagtaccac actgaaaatt agacatttat taaccaaatt taacgtggta 5100 tttaaaggta atatttttaa tatgatacat tacatattgt gaatgtatac taaaaaaaca 5160 ttttaaatgt taaaattata atttcagatt catataacca caactgtgat atatcctaac 5220 tataaccagt tgttgagggg tatactagaa gcagaatgaa accacatttt ttggtttgat 5280 aatatgcact tattgactcc cactcattgt tatgttaatt aagttattat tctgtctcct 5340 tgtaattttg attacaaaaa ttttattatc ctgagttagc tgttactttt acagtacctg 5400 atactcctaa aacttttaac ttatacaaat tagtcaataa tgaccccaat tttttcatta 5460 aaataatagt ggtgaattat atgttattgt gttaaaacct cacttgccaa attctggctt 5520 cacatttgta tttagggcta tccttaaaat gatgagtcta tattatctag ctttctatta 5580 ccctaatata aactggtata agaagacttt ccttttttct ttatgcatgg aagcatcaat 5640 aaattgttta aaaaccatgt atagtaaatt cagcttaacc cgtgatcttc ttaagttaaa 5700 ggtacttttg ttttataaaa gctctagata aaactttctt ttctgatcat gaatcaagta 5760 tctgtggttt catgcccctc tctatacctt tcaaagaact cctgaagcaa cttaactcat 5820 catttcagcc tctgagtaga ggtaaaacct atgtgtactt ctgtttatga tccatattga 5880 tatttatgac atgaacacag aatagtacct tacatttgct aaacagacag ttaatatcaa 5940 atcctttcaa tattctggga acccagggaa gtttttaaaa atgtcattac tttcaaagga 6000 acagaagtag ttaaccaaac taacaagcaa aacctgaggt ttacctagtg acaccaaatt 6060 atcggtattt taactgaatt tacccattga ctaagaatga accagatttg gtggtggttt 6120 tgtttctatg caaactggac acaaattaca acagtaaatt tttttataag tgcttctccc 6180 ttctccatga tgtgacttcc ggagataaag gattcaaaag ataaagacaa agtacgctca 6240 gagttgttaa ccagaaagtc ctggctgtgg ttgcagaaac actgttggaa gaaaagagat 6300 gactaagtca agtgtctgcc ttatcaaaag agcaaaaatg cctctggttt tgtgtttggg 6360 agaaaagtat cttggacgca ctgttttcct tgataaaagt catcttctct actgtgtgaa 6420 atgaatactt ggaattctaa ttgttttgtg tgccaggggc agtaatgtcc ctgcctcttc 6480 tcccaatcaa ggttgaggag tggggctggg gagaggactt aactgactta agaagtagga 6540 aaacaaaaac ctctctcctc agccttccac ctccaagaga ggaggaaaaa cagttgtctg 6600 ctgtctgtaa ttcagtttgc gtgtatttta tgctcatgca ccaacccata cagagtaaat 6660 cttttatcaa ctgtatactg gtgtttaata gagaatgatt gtcttccgag ttttttggtt 6720 ccttttttaa ctgtgttaaa gtacttgaaa tgtattgact gctgactata ttttaaaaac 6780 aaaatgaaat aatttgagtt gtattacaga ggttgacatt gttcagggat gggacaaagc 6840 cttcttcaat ccttttcata ctacttaatg attttggtgc aggaacctga gattttctga 6900 tttatatttc atgatatttc acatttgctc ttcacagcat gagcatgaag cccagtggca 6960 ccaaatggct gggtacaatc aagtgatatt ttgtagcacc tcactatctg aaaggccatg 7020 agttttcaga tgatttcatt gagcttcatt gcagcctgaa attttaaaaa agttgtgtaa 7080 tacgccaacc agtcaagttg tgttttggcc agagatttag atatgtccaa tttcctggct 7140 catttcattg tgctctatgg gtacgtataa aaagcaagaa ttctgtttcc taggcaaaca 7200 ttgcaactca gggctaaagt catccagtga aacttttaga gccagaagta actttgtccc 7260 agtcctacaa tgtgaaaaga gtgaatagtt gcctcttttt agccattttc atggctggta 7320 catattcgta cgcattactt ttcagaatca atacgcactt tcagatattc ttatttttat 7380 tctcttaagt ctttattaac tttggagaga gaaatgatgc atctttttat tttaaatgaa 7440 gtagatcaac atggtggaac aaaatgataa agaacagaaa acatttcaat atattactaa 7500 taactttttc caatataaat cctaaaattc ctataacata gtattttaca gttttatgaa 7560 gctttctatt gtgactttta tggaattaag agatgaagaa gatgagatat tttagcattt 7620 atatttttca aaattatatg tatacttaaa aataaagtaa ctttatgca 7669 <![CDATA[<210> 134]]> <![CDATA[<211> 4662]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 134]]> agagcagccc ggagaccgct gccgccgctg ccgctgctac caccgctgcc acctgaggag 60 acccgccgcc cccccgtcgc cgcctcctgc gagtccttct tagcacctgg cgtttcatgc 120 acattgccac tgccattatt attatcattc caatacaagg aaaataaaag aagataccag 180 cgaaaagaac cgcttacacc tttccgaatt actcaagtgt ctcctggaaa cagagggtcg 240 ttgtccccgg aggagcagcc gaagggcccg tgggctggtg ttgaccggga gggaggagga 300 gttgggggca ttgcgtggtg gaaagttgcg tgcggcagag aaccgaaggt gcagcgccac 360 agcccagggg acggtgtgtc tgggagaaga cgctgcccct gcgtcgggac ccgccagcgc 420 gcgggcaccg cggggcccgg gacgacgccc cctcctgcgg cgtggactcc gtcagtggcc 480 caccaagaag gaggaggaat atggaatcca agggggccag ttcctgccgt ctgctcttct 540 gcctcttgat ctccgccacc gtcttcaggc caggccttgg atggtatact gtaaattcag 600 catatggaga taccattatc ataccttgcc gacttgacgt acctcagaat ctcatgtttg 660 gcaaatggaa atatgaaaag cccgatggct ccccagtatt tattgccttc agatcctcta 720 caaagaaaag tgtgcagtac gacgatgtac cagaatacaa agacagattg aacctctcag 780 aaaactacac tttgtctatc agtaatgcaa ggatcagtga tgaaaagaga tttgtgtgca 840 tgctagtaac tgaggacaac gtgtttgagg cacctacaat agtcaaggtg ttcaagcaac 900 catctaaacc tgaaattgta agcaaagcac tgtttctcga aacagagcag ctaaaaaagt 960 tgggtgactg catttcagaa gacagttatc cagatggcaa tatcacatgg tacaggaatg 1020 gaaaagtgct acatcccctt gaaggagcgg tggtcataat ttttaaaaag gaaatggacc 1080 cagtgactca gctctatacc atgacttcca ccctggagta caagacaacc aaggctgaca 1140 tacaaatgcc attcacctgc tcggtgacat attatggacc atctggccag aaaacaattc 1200 attctgaaca ggcagtattt gatatttact atcctacaga gcaggtgaca atacaagtgc 1260 tgccaccaaa aaatgccatc aaagaagggg ataacatcac tcttaaatgc ttagggaatg 1320 gcaaccctcc cccagaggaa tttttgtttt acttaccagg acagcccgaa ggaataagaa 1380 gctcaaatac ttacacactg acggatgtga ggcgcaatgc aacaggagac tacaagtgtt 1440 ccctgataga caaaaaaagc atgattgctt caacagctat cacagttcac tatttggatt 1500 tgtccttaaa cccaagtgga gaagtgacta gacagattgg tgatgcccta cccgtgtcat 1560 gcacaatatc tgctagcagg aatgcaactg tggtatggat gaaagataac atcaggcttc 1620 gatctagccc gtcattttct agtcttcatt atcaggatgc tggaaactat gtctgcgaaa 1680 ctgctctgca ggaggttgaa ggactaaaga aaagagagtc attgactctc attgtagaag 1740 gcaaacctca aataaaaatg acaaagaaaa ctgatcccag tggactatct aaaacaataa 1800 tctgccatgt ggaaggtttt ccaaagccag ccattcaatg gacaattact ggcagtggaa 1860 gcgtcataaa ccaaacagag gaatctcctt atattaatgg caggtattat agtaaaatta 1920 tcatttcccc tgaagagaat gttacattaa cttgcacagc agaaaaccaa ctggagagaa 1980 cagtaaactc cttgaatgtc tctgctaatg aaaacagaga aaaggtgaat gaccaggcaa 2040 aactaattgt gggaatcgtt gttggtctcc tccttgctgc ccttgttgct ggtgtcgtct 2100 actggctgta catgaagaag tcaaagactg catcaaaaca tgtaaacaag gacctcggta 2160 atatggaaga aaacaaaaag ttagaagaaa acaatcacaa aactgaagcc taagagagaa 2220 actgtcctag ttgtccagag ataaaaatca tatagaccaa ttgaagcatg aacgtggatt 2280 gtatttaaga cataaacaaa gacattgaca gcaattcatg gttcaagtat taagcagttc 2340 attctaccaa gctgtcacag gttttcagag aattatctca agtaaaacaa atgaaattta 2400 attacaaaca ataagaacaa gttttggcag ccatgataat aggtcatatg ttgtgtttgg 2460 ttcaattttt tttccgtaaa tgtctgcact gaggatttct ttttggtttg ccttttatgt 2520 aaatttttta cgtagctatt tttatacact gtaagctttg ttctgggagt tgctgttaat 2580 ctgatgtata atgtaatgtt tttatttcaa ttgtttatat ggataatctg agcaggtaca 2640 tttctgattc tgattgctat cagcaatgcc ccaaactttc tcataagcac ctaaaaccca 2700 aaggtggcag cttgtgaaga ttggggacac tcatattgcc ctaattaaaa actgtgattt 2760 ttatcacaag ggaggggagg ccgagagtca gactgataga caccatagga gccgactctt 2820 tgatatgcca ccagcgaact ctcagaaata aatcacagat gcatatagac acacatacat 2880 aatggtactc ccaaactgac aattttacct attctgaaaa agacataaaa cagaatttgg 2940 tagcacttac ctctacagac acctgctaat aaattatttt ctgtcaaaag aaaaaacaca 3000 agcatgtgtg agagacagtt tggaaaaatc atggtcaaca ttcccatttt catagatcac 3060 aatgtaaatc actataatta caaattggtg ttaaatcctt tgggttatcc actgccttaa 3120 aattatacct atttcatgtt taaaaagata tcaatcagaa ttggagtttt taacagtggt 3180 cattatcaaa gctgtgttat tttccacaga atatagaata tatatttttt tcgtgtgtgt 3240 ttttgttaac taccctacag atattgaatg caccttgaga taatttagtg tttttaactg 3300 atacataatt tatcaagcag tacatgaaag tgtaataata aaatgtctat gtatctttag 3360 ttacattcaa atttgtaact ttataaacat gttttatgct tgaggaaatt tttaaggtgg 3420 tagtataaat ggaaactttt tgaagtagac cagatatggg ctacttgtga ctagactttt 3480 aaactttgct ctttcaagca gaagcctggt ttctgggaga acactgcaca gcgatttctt 3540 tcccaggatt tacacaactt taaagggaag ataaatgaac atcagatttc taggtataga 3600 actatgttat tgaaaggaaa aggaaaactg gtgtttgttt cttagactca tgaaataaaa 3660 aattatgaag gcaatgaaaa ataaattgaa aattaaagtc agatgagaat aggaataata 3720 ctttgccact tctgcattat ttagaaacat acgttattgt acatttgtaa accatttact 3780 gtctgggcaa tagtgactcc gtttaataaa agcttccgta gtgcattggt atggattaaa 3840 tgcataaaat attcttagac tcgatgctgt ataaaatatt atgggaaaaa aagaaaatac 3900 gttattttgc ctctaaactt ttattgaagt tttatttggc aggaaaaaaa attgaatctt 3960 ggtcaacatt taaaccaaag taaaagggga aaaaccaaag ttatttgttt tgcatggcta 4020 agccattctg ttatctctgt aaatactgtg atttcttttt tattttctct ttagaatttt 4080 gttaaagaaa ttctaaaatt tttaaacacc tgctctccac aataaatcac aaacactaaa 4140 ataaaattac ttccatataa atattatttt ctcttttggt gtgggagatc aaaggtttaa 4200 agtctaactt ctaagatata tttgcagaaa gaagcaacat gacaatagag agagttatgc 4260 tacaattatt tcttggtttc cacttgcaat ggttaattaa gtccaaaaac agctgtcaga 4320 acctcgagag cagaacatga gaaactcaga gctctggacc gaaagcagaa agtttgccgg 4380 gaaaaaaaaa gacaacatta ttaccatcga ttcagtgcct ggataaagag gaaagcttac 4440 ttgtttaatg gcagccacat gcacgaagat gctaagaaga aaaagaattc caaatcctca 4500 acttttgagg tttcggctct ccaatttaac tctttggcaa caggaaacag gttttgcaag 4560 ttcaaggttc actccctata tgtgattata ggaattgttt gtggaaatgg attaacatac 4620 ccgtctatgc ctaaaagata ataaaactga aatatgtctt ca 4662 <![CDATA[<210> 135]]> <![CDATA[<211> 2750]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 135]]> agagcagccc ggagaccgct gccgccgctg ccgctgctac caccgctgcc acctgaggag 60 acccgccgcc cccccgtcgc cgcctcctgc gagtccttct tagcacctgg cgtttcatgc 120 acattgccac tgccattatt attatcattc caatacaagg aaaataaaag aagataccag 180 cgaaaagaac cgcttacacc tttccgaatt actcaagtgt ctcctggaaa cagagggtcg 240 ttgtccccgg aggagcagcc gaagggcccg tgggctggtg ttgaccggga gggaggagga 300 gttgggggca ttgcgtggtg gaaagttgcg tgcggcagag aaccgaaggt gcagcgccac 360 agcccagggg acggtgtgtc tgggagaaga cgctgcccct gcgtcgggac ccgccagcgc 420 gcgggcaccg cggggcccgg gacgacgccc cctcctgcgg cgtggactcc gtcagtggcc 480 caccaagaag gaggaggaat atggaatcca agggggccag ttcctgccgt ctgctcttct 540 gcctcttgat ctccgccacc gtcttcaggc caggccttgg atggtatact gtaaattcag 600 catatggaga taccattatc ataccttgcc gacttgacgt acctcagaat ctcatgtttg 660 gcaaatggaa atatgaaaag cccgatggct ccccagtatt tattgccttc agatcctcta 720 caaagaaaag tgtgcagtac gacgatgtac cagaatacaa agacagattg aacctctcag 780 aaaactacac tttgtctatc agtaatgcaa ggatcagtga tgaaaagaga tttgtgtgca 840 tgctagtaac tgaggacaac gtgtttgagg cacctacaat agtcaaggtg ttcaagcaac 900 catctaaacc tgaaattgta agcaaagcac tgtttctcga aacagagcag ctaaaaaagt 960 tgggtgactg catttcagaa gacagttatc cagatggcaa tatcacatgg tacaggaatg 1020 gaaaagtgct acatcccctt gaaggagcgg tggtcataat ttttaaaaag gaaatggacc 1080 cagtgactca gctctatacc atgacttcca ccctggagta caagacaacc aaggctgaca 1140 tacaaatgcc attcacctgc tcggtgacat attatggacc atctggccag aaaacaattc 1200 attctgaaca ggcagtattt gatatttact atcctacaga gcaggtgaca atacaagtgc 1260 tgccaccaaa aaatgccatc aaagaagggg ataacatcac tcttaaatgc ttagggaatg 1320 gcaaccctcc cccagaggaa tttttgtttt acttaccagg acagcccgaa ggaataagaa 1380 gctcaaatac ttacacactg acggatgtga ggcgcaatgc aacaggagac tacaagtgtt 1440 ccctgataga caaaaaaagc atgattgctt caacagctat cacagttcac tatttggatt 1500 tgtccttaaa cccaagtgga gaagtgacta gacagattgg tgatgcccta cccgtgtcat 1560 gcacaatatc tgctagcagg aatgcaactg tggtatggat gaaagataac atcaggcttc 1620 gatctagccc gtcattttct agtcttcatt atcaggatgc tggaaactat gtctgcgaaa 1680 ctgctctgca ggaggttgaa ggactaaaga aaagagagtc attgactctc attgtagaag 1740 gcaaacctca aataaaaatg acaaagaaaa ctgatcccag tggactatct aaaacaataa 1800 tctgccatgt ggaaggtttt ccaaagccag ccattcaatg gacaattact ggcagtggaa 1860 gcgtcataaa ccaaacagag gaatctcctt atattaatgg caggtattat agtaaaatta 1920 tcatttcccc tgaagagaat gttacattaa cttgcacagc agaaaaccaa ctggagagaa 1980 cagtaaactc cttgaatgtc tctgctataa gtattccaga acacgatgag gcagacgaga 2040 taagtgatga aaacagagaa aaggtgaatg accaggcaaa actaattgtg ggaatcgttg 2100 ttggtctcct ccttgctgcc cttgttgctg gtgtcgtcta ctggctgtac atgaagaagt 2160 caaagtgagt tgtggaaaaa agatcttcat cgttcattga ctttcactgg gagaaaatac 2220 aatgtgctaa ttttgctcac tccagtcgtg catataattt atacaataag gaagatgtat 2280 ccccaaatca ggttgattat atattttgtt tcaactaatt ttgactacac tgcctttgtc 2340 agggacatgg cttgggatac tgtttcacat gtgtccgttt atttgtctca atcaatagcc 2400 tgaattcaat tatttgattt tttcagtgct tgagtgaatt ttttaaagcg tatacttcct 2460 aaaggtcaac aaccatagac tttttggttg aagttggaga agattcatta aaagtaccta 2520 gtacatcttg tagggactgc caggtgtctt tgcagtgaca catctggcca gcaatgaaac 2580 tgctgctgag gtaggaatat cttattgtta ttactcccat attctagtta gttgactttg 2640 atccatataa gagtctatat cagagaaaat catgtcatta tgtcaacttg agtttttaaa 2700 aatggattaa agtaccaaca ctacattaaa aatgctttag agatgttaaa 2750 <![CDATA[<210> 136]]> <![CDATA[<211> 1773]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 136]]> agagcagccc ggagaccgct gccgccgctg ccgctgctac caccgctgcc acctgaggag 60 acccgccgcc cccccgtcgc cgcctcctgc gagtccttct tagcacctgg cgtttcatgc 120 acattgccac tgccattatt attatcattc caatacaagg aaaataaaag aagataccag 180 cgaaaagaac cgcttacacc tttccgaatt actcaagtgt ctcctggaaa cagagggtcg 240 ttgtccccgg aggagcagcc gaagggcccg tgggctggtg ttgaccggga gggaggagga 300 gttgggggca ttgcgtggtg gaaagttgcg tgcggcagag aaccgaaggt gcagcgccac 360 agcccagggg acggtgtgtc tgggagaaga cgctgcccct gcgtcgggac ccgccagcgc 420 gcgggcaccg cggggcccgg gacgacgccc cctcctgcgg cgtggactcc gtcagtggcc 480 caccaagaag gaggaggaat atggaatcca agggggccag ttcctgccgt ctgctcttct 540 gcctcttgat ctccgccacc gtcttcaggc caggccttgg atggtatact gtaaattcag 600 catatggaga taccattatc ataccttgcc gacttgacgt acctcagaat ctcatgtttg 660 gcaaatggaa atatgaaaag cccgatggct ccccagtatt tattgccttc agatcctcta 720 caaagaaaag tgtgcagtac gacgatgtac cagaatacaa agacagattg aacctctcag 780 aaaactacac tttgtctatc agtaatgcaa ggatcagtga tgaaaagaga tttgtgtgca 840 tgctagtaac tgaggacaac gtgtttgagg cacctacaat agtcaaggtg ttcagtaagt 900 agtctgcagc agtgtcactg ctaagtggga ttgatggcca gtaccagacc atgttcttta 960 gaaagaagac tgaactctct gtagtgtctc tatagcaggt atctatataa ggggacttaa 1020 agagatcttc attctgctca tatatactat cagcaaagaa aacaaagagt atgaaattca 1080 aataggagat ttgcagtgag gaactaaaat aatattctct gttactttgt catgtaaaaa 1140 tgtcgtgagc tatgaagtac tactactgat aactagcagg tgatcttaat ttttactgac 1200 atgtacaaat aagtgttgtg tgatacatac atagatatat gatatatatg taatcatgta 1260 tatcacgcat acatatacat gtatttggct gaaccaaatg aaattgccat tttgctgcat 1320 aataaaaaaa tataagcaaa ttcaaactat attttaacag aggtataaat tttccattta 1380 tatatatcca catatataaa tatcccatat atatccacat acaaatattt tatatattat 1440 atatattaga gatatagata catttccatc ctgaccttta ttgactggtt attgatttag 1500 atttcaaaaa gtattcactt gctttagaaa attgtcctaa aattaaaaaa actcactata 1560 ccctgaatgc ttatgtggga tacaccaagg ggagaaagta gagtagtgat ggaagaagag 1620 aaaattgtag aagaaacttg gaataattat agtcactatg acaaaattac tttgcctaat 1680 gatagcatat agttaatgtt actgtgcaaa taactgtgca aatgaatgac ttgagaagtt 1740 ataattaaag tatttcatct tttaaaactc aaa 1773 <![CDATA[<210> 137]]> <![CDATA[<211> 4701]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 137]]> agagcagccc ggagaccgct gccgccgctg ccgctgctac caccgctgcc acctgaggag 60 acccgccgcc cccccgtcgc cgcctcctgc gagtccttct tagcacctgg cgtttcatgc 120 acattgccac tgccattatt attatcattc caatacaagg aaaataaaag aagataccag 180 cgaaaagaac cgcttacacc tttccgaatt actcaagtgt ctcctggaaa cagagggtcg 240 ttgtccccgg aggagcagcc gaagggcccg tgggctggtg ttgaccggga gggaggagga 300 gttgggggca ttgcgtggtg gaaagttgcg tgcggcagag aaccgaaggt gcagcgccac 360 agcccagggg acggtgtgtc tgggagaaga cgctgcccct gcgtcgggac ccgccagcgc 420 gcgggcaccg cggggcccgg gacgacgccc cctcctgcgg cgtggactcc gtcagtggcc 480 caccaagaag gaggaggaat atggaatcca agggggccag ttcctgccgt ctgctcttct 540 gcctcttgat ctccgccacc gtcttcaggc caggccttgg atggtatact gtaaattcag 600 catatggaga taccattatc ataccttgcc gacttgacgt acctcagaat ctcatgtttg 660 gcaaatggaa atatgaaaag cccgatggct ccccagtatt tattgccttc agatcctcta 720 caaagaaaag tgtgcagtac gacgatgtac cagaatacaa agacagattg aacctctcag 780 aaaactacac tttgtctatc agtaatgcaa ggatcagtga tgaaaagaga tttgtgtgca 840 tgctagtaac tgaggacaac gtgtttgagg cacctacaat agtcaaggtg ttcaagcaac 900 catctaaacc tgaaattgta agcaaagcac tgtttctcga aacagagcag ctaaaaaagt 960 tgggtgactg catttcagaa gacagttatc cagatggcaa tatcacatgg tacaggaatg 1020 gaaaagtgct acatcccctt gaaggagcgg tggtcataat ttttaaaaag gaaatggacc 1080 cagtgactca gctctatacc atgacttcca ccctggagta caagacaacc aaggctgaca 1140 tacaaatgcc attcacctgc tcggtgacat attatggacc atctggccag aaaacaattc 1200 attctgaaca ggcagtattt gatatttact atcctacaga gcaggtgaca atacaagtgc 1260 tgccaccaaa aaatgccatc aaagaagggg ataacatcac tcttaaatgc ttagggaatg 1320 gcaaccctcc cccagaggaa tttttgtttt acttaccagg acagcccgaa ggaataagaa 1380 gctcaaatac ttacacactg acggatgtga ggcgcaatgc aacaggagac tacaagtgtt 1440 ccctgataga caaaaaaagc atgattgctt caacagctat cacagttcac tatttggatt 1500 tgtccttaaa cccaagtgga gaagtgacta gacagattgg tgatgcccta cccgtgtcat 1560 gcacaatatc tgctagcagg aatgcaactg tggtatggat gaaagataac atcaggcttc 1620 gatctagccc gtcattttct agtcttcatt atcaggatgc tggaaactat gtctgcgaaa 1680 ctgctctgca ggaggttgaa ggactaaaga aaagagagtc attgactctc attgtagaag 1740 gcaaacctca aataaaaatg acaaagaaaa ctgatcccag tggactatct aaaacaataa 1800 tctgccatgt ggaaggtttt ccaaagccag ccattcaatg gacaattact ggcagtggaa 1860 gcgtcataaa ccaaacagag gaatctcctt atattaatgg caggtattat agtaaaatta 1920 tcatttcccc tgaagagaat gttacattaa cttgcacagc agaaaaccaa ctggagagaa 1980 cagtaaactc cttgaatgtc tctgctataa gtattccaga acacgatgag gcagacgaga 2040 taagtgatga aaacagagaa aaggtgaatg accaggcaaa actaattgtg ggaatcgttg 2100 ttggtctcct ccttgctgcc cttgttgctg gtgtcgtcta ctggctgtac atgaagaagt 2160 caaagactgc atcaaaacat gtaaacaagg acctcggtaa tatggaagaa aacaaaaagt 2220 tagaagaaaa caatcacaaa actgaagcct aagagagaaa ctgtcctagt tgtccagaga 2280 taaaaatcat atagaccaat tgaagcatga acgtggattg tatttaagac ataaacaaag 2340 acattgacag caattcatgg ttcaagtatt aagcagttca ttctaccaag ctgtcacagg 2400 ttttcagaga attatctcaa gtaaaacaaa tgaaatttaa ttacaaacaa taagaacaag 2460 ttttggcagc catgataata ggtcatatgt tgtgtttggt tcaatttttt ttccgtaaat 2520 gtctgcactg aggatttctt tttggtttgc cttttatgta aattttttac gtagctattt 2580 ttatacactg taagctttgt tctgggagtt gctgttaatc tgatgtataa tgtaatgttt 2640 ttatttcaat tgtttatatg gataatctga gcaggtacat ttctgattct gattgctatc 2700 agcaatgccc caaactttct cataagcacc taaaacccaa aggtggcagc ttgtgaagat 2760 tggggacact catattgccc taattaaaaa ctgtgatttt tatcacaagg gaggggaggc 2820 cgagagtcag actgatagac accataggag ccgactcttt gatatgccac cagcgaactc 2880 tcagaaataa atcacagatg catatagaca cacatacata atggtactcc caaactgaca 2940 attttaccta ttctgaaaaa gacataaaac agaatttggt agcacttacc tctacagaca 3000 cctgctaata aattattttc tgtcaaaaga aaaaacacaa gcatgtgtga gagacagttt 3060 ggaaaaatca tggtcaacat tcccattttc atagatcaca atgtaaatca ctataattac 3120 aaattggtgt taaatccttt gggttatcca ctgccttaaa attataccta tttcatgttt 3180 aaaaagatat caatcagaat tggagttttt aacagtggtc attatcaaag ctgtgttatt 3240 ttccacagaa tatagaatat atattttttt cgtgtgtgtt tttgttaact accctacaga 3300 tattgaatgc accttgagat aatttagtgt ttttaactga tacataattt atcaagcagt 3360 acatgaaagt gtaataataa aatgtctatg tatctttagt tacattcaaa tttgtaactt 3420 tataaacatg ttttatgctt gaggaaattt ttaaggtggt agtataaatg gaaacttttt 3480 gaagtagacc agatatgggc tacttgtgac tagactttta aactttgctc tttcaagcag 3540 aagcctggtt tctgggagaa cactgcacag cgatttcttt cccaggattt acacaacttt 3600 aaagggaaga taaatgaaca tcagatttct aggtatagaa ctatgttatt gaaaggaaaa 3660 ggaaaactgg tgtttgtttc ttagactcat gaaataaaaa attatgaagg caatgaaaaa 3720 taaattgaaa attaaagtca gatgagaata ggaataatac tttgccactt ctgcattatt 3780 tagaaacata cgttattgta catttgtaaa ccatttactg tctgggcaat agtgactccg 3840 tttaataaaa gcttccgtag tgcattggta tggattaaat gcataaaata ttcttagact 3900 cgatgctgta taaaatatta tgggaaaaaa agaaaatacg ttattttgcc tctaaacttt 3960 tattgaagtt ttatttggca ggaaaaaaaa ttgaatcttg gtcaacattt aaaccaaagt 4020 aaaaggggaa aaaccaaagt tatttgtttt gcatggctaa gccattctgt tatctctgta 4080 aatactgtga tttctttttt attttctctt tagaattttg ttaaagaaat tctaaaattt 4140 ttaaacacct gctctccaca ataaatcaca aacactaaaa taaaattact tccatataaa 4200 tattattttc tcttttggtg tgggagatca aaggtttaaa gtctaacttc taagatatat 4260 ttgcagaaag aagcaacatg acaatagaga gagttatgct acaattattt cttggtttcc 4320 acttgcaatg gttaattaag tccaaaaaca gctgtcagaa cctcgagagc agaacatgag 4380 aaactcagag ctctggaccg aaagcagaaa gtttgccggg aaaaaaaaag acaacattat 4440 taccatcgat tcagtgcctg gataaagagg aaagcttact tgtttaatgg cagccacatg 4500 cacgaagatg ctaagaagaa aaagaattcc aaatcctcaa cttttgaggt ttcggctctc 4560 caatttaact ctttggcaac aggaaacagg ttttgcaagt tcaaggttca ctccctatat 4620 gtgattatag gaattgtttg tggaaatgga ttaacatacc cgtctatgcc taaaagataa 4680 taaaactgaa atatgtcttc a 4701 <![CDATA[<210> 138]]> <![CDATA[<211> 2551]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 138]]> agtccggggg catcgcgatg ctgctgcgcc tgttgctggc ctgggcggcc gcagggccca 60 cactgggcca ggacccctgg gctgctgagc cccgtgccgc ctgcggcccc agcagctgct 120 acgctctctt cccacggcgc cgcaccttcc tggaggcctg gcgggcctgc cgcgagctgg 180 ggggcgacct ggccactcct cggacccccg aggaggccca gcgtgtggac agcctggtgg 240 gtgcgggccc agccagccgg ctgctgtgga tcgggctgca gcggcaggcc cggcaatgcc 300 agctgcagcg cccactgcgc ggcttcacgt ggaccacagg ggaccaggac acggctttca 360 ccaactgggc ccagccagcc tctggaggcc cctgcccggc ccagcgctgt gtggccctgg 420 aggcaagtgg cgagcaccgc tggctggagg gctcgtgcac gctggctgtc gacggctacc 480 tgtgccagtt tggcttcgag ggcgcctgcc cggcgctgca agatgaggcg ggccaggccg 540 gcccagccgt gtataccacg cccttccacc tggtctccac agagtttgag tggctgccct 600 tcggctctgt ggccgctgtg cagtgccagg ctggcagggg agcctctctg ctctgcgtga 660 agcagcctga gggaggtgtg ggctggtcac gggctgggcc cctgtgcctg gggactggct 720 gcagccctga caacgggggc tgcgaacacg aatgtgtgga ggaggtggat ggtcacgtgt 780 cctgccgctg cactgagggc ttccggctgg cagcagacgg gcgcagttgc gaggacccct 840 gtgcccaggc tccgtgcgag cagcagtgtg agcccggtgg gccacaaggc tacagctgcc 900 actgtcgcct gggtttccgg ccagcggagg atgatccgca ccgctgtgtg gacacagatg 960 agtgccagat tgccggtgtg tgccagcaga tgtgtgtcaa ctacgttggt ggcttcgagt 1020 gttattgtag cgagggacat gagctggagg ctgatggcat cagctgcagc cctgcagggg 1080 ccatgggtgc ccaggcttcc caggacctcg gagatgagtt gctggatgac ggggaggatg 1140 aggaagatga agacgaggcc tggaaggcct tcaacggtgg ctggacggag atgcctggga 1200 tcctgtggat ggagcctacg cagccgcctg actttgccct ggcctataga ccgagcttcc 1260 cagaggacag agagccacag ataccctacc cggagcccac ctggccaccc ccgctcagtg 1320 cccccagggt cccctaccac tcctcagtgc tctccgtcac ccggcctgtg gtggtctctg 1380 ccacgcatcc cacactgcct tctgcccacc agcctcctgt gatccctgcc acacacccag 1440 ctttgtcccg tgaccaccag atccccgtga tcgcagccaa ctatccagat ctgccttctg 1500 cctaccaacc cggtattctc tctgtctctc attcagcaca gcctcctgcc caccagcccc 1560 ctatgatctc aaccaaatat ccggagctct tccctgccca ccagtccccc atgtttccag 1620 acacccgggt cgctggcacc cagaccacca ctcatttgcc tggaatccca cctaaccatg 1680 cccctctggt caccaccctc ggtgcccagc taccccctca agccccagat gcccttgtcc 1740 tcagaaccca ggccacccag cttcccatta tcccaactgc ccagccctct ctgaccacca 1800 cctccaggtc ccctgtgtct cctgcccatc aaatctctgt gcctgctgcc acccagcccg 1860 cagccctccc caccctcctg ccctctcaga gccccactaa ccagacctca cccatcagcc 1920 ctacacatcc ccattccaaa gccccccaaa tcccaaggga agatggcccc agtcccaagt 1980 tggccctgtg gctgccctca ccagctccca cagcagcccc aacagccctg ggggaggctg 2040 gtcttgccga gcacagccag agggatgacc ggtggctgct ggtggcactc ctggtgccaa 2100 cgtgtgtctt tttggtggtc ctgcttgcac tgggcatcgt gtactgcacc cgctgtggcc 2160 cccatgcacc caacaagcgc atcactgact gctatcgctg ggtcatccat gctgggagca 2220 agagcccaac agaacccatg ccccccaggg gcagcctcac aggggtgcag acctgcagaa 2280 ccagcgtgtg atggggtgca gacccccctc atggagtatg gggcgctgga cacatggccg 2340 gggctgcacc agggacccat gggggctgcc cagctggaca gatggcttcc tgctccccag 2400 gcccagccag ggtcctctct caaccactag acttggctct caggaactct gcttcctggc 2460 ccagcgctcg tgaccaagga tacaccaaag cccttaagac ctcagggggc gggtgctggg 2520 gtcttctcca ataaatgggg tgtcaacctt a 2551 <![CDATA[<210> 139]]> <![CDATA[<211> 1480]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 139]]> agcatcttcg taagcctgga ttgctcacca gctttcattt cagctcctgt aggcatctcc 60 tgaattaagc aacacagaaa agtcctctga agtcactgaa tcccataaag gctctctacc 120 tttagcacaa gggaggtctt caccactgga caaagaagga acgataaggg gtcatcagac 180 tggggtttct gagcatggat tcaaccatcc cagtcttggg tacagaactg acaccaatca 240 acggacgtga ggagactcct tgctacaagc agaccctgag cttcacgggg ctgacgtgca 300 tcgtttccct tgtcgcgctg acaggaaacg cggttgtgct ctggctcctg ggctgccgca 360 tgcgcaggaa cgctgtctcc atctacatcc tcaacctggt cgcggccgac ttcctcttcc 420 ttagcggcca cattatatgt tcgccgttac gcctcatcaa tatccgccat cccatctcca 480 aaatcctcag tcctgtgatg acctttccct actttatagg cctaagcatg ctgagcgcca 540 tcagcaccga gcgctgcctg tccatcctgt ggcccatctg gtaccactgc cgccgcccca 600 gatacctgtc atcagtcatg tgtgtcctgc tctgggccct gtccctgctg cggagtatcc 660 tggagtggat gttctgtgac ttcctgttta gtggtgctaa ttctgtttgg tgtgaaacgt 720 cagatttcat tacaatcgcg tggctggttt ttttatgtgt ggttctctgt gggtccagcc 780 tggtcctgct ggtcaggatt ctctgtggat cccggaagat gccgctgacc aggctgtacg 840 tgaccatcct cctcacagtg ctggtcttcc tcctctgtgg cctgcccttt ggcattcagt 900 gggccctgtt ttccaggatc cacctggatt ggaaagtctt attttgtcat gtgcatctag 960 tttccatttt cctgtccgct cttaacagca gtgccaaccc catcatttac ttcttcgtgg 1020 gctcctttag gcagcgtcaa aataggcaga acctgaagct ggttctccag agggctctgc 1080 aggacacgcc tgaggtggat gaaggtggag ggtggcttcc tcaggaaacc ctggagctgt 1140 cgggaagcag attggagcag tgaggaagaa cctctgccct gtcagacagg actttgagag 1200 caatgctgcc ctgccaccct tgacaattat atgcattttt cttagccttc tgcctcagaa 1260 atgtctcagt ggtccctcaa ggtcttcgaa tagatgttta tctaacctga cagttgcagt 1320 tttcacccat ggaaagcatt agtctgacag tacaatgttt ggattctcct tgatattacc 1380 aatacatttt ccctgttatc ttgcactgaa tctttcctac tgaacacttt ttctgcactt 1440 ttcattgtaa taaaaggagt tgctgtccac aaccctaaaa 1480 <![CDATA[<210> 140]]> <![CDATA[<211> 1647]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 140]]> gcccagtctg gaaagtgagg agcgtctttg cccggccgcc atcccatcta ggaagtgagg 60 agcgcctctt cccggccgcc atcccatcta ggaagtgagg agcgtctctg cccggccgcc 120 catcgtctga gatgtgggga gtgcctttgc cccgccgccc cgtctgggat gtgaggagcg 180 cctctgcccg gtcgcgaccc cgtctgggag ctcctgtagg catctcctga attaagcaac 240 acagaaaagt cctctgaagt cactgaatcc cataaaggct ctctaccttt agcacaaggg 300 aggtcttcac cactggacaa agaaggaacg ataaggggtc atcagactgg ggtttctgag 360 catggattca accatcccag tcttgggtac agaactgaca ccaatcaacg gacgtgagga 420 gactccttgc tacaagcaga ccctgagctt cacggggctg acgtgcatcg tttcccttgt 480 cgcgctgaca ggaaacgcgg ttgtgctctg gctcctgggc tgccgcatgc gcaggaacgc 540 tgtctccatc tacatcctca acctggtcgc ggccgacttc ctcttcctta gcggccacat 600 tatatgttcg ccgttacgcc tcatcaatat ccgccatccc atctccaaaa tcctcagtcc 660 tgtgatgacc tttccctact ttataggcct aagcatgctg agcgccatca gcaccgagcg 720 ctgcctgtcc atcctgtggc ccatctggta ccactgccgc cgccccagat acctgtcatc 780 agtcatgtgt gtcctgctct gggccctgtc cctgctgcgg agtatcctgg agtggatgtt 840 ctgtgacttc ctgtttagtg gtgctaattc tgtttggtgt gaaacgtcag atttcattac 900 aatcgcgtgg ctggtttttt tatgtgtggt tctctgtggg tccagcctgg tcctgctggt 960 caggattctc tgtggatccc ggaagatgcc gctgaccagg ctgtacgtga ccatcctcct 1020 cacagtgctg gtcttcctcc tctgtggcct gccctttggc attcagtggg ccctgttttc 1080 caggatccac ctggattgga aagtcttatt ttgtcatgtg catctagttt ccattttcct 1140 gtccgctctt aacagcagtg ccaaccccat catttacttc ttcgtgggct cctttaggca 1200 gcgtcaaaat aggcagaacc tgaagctggt tctccagagg gctctgcagg acacgcctga 1260 ggtggatgaa ggtggagggt ggcttcctca ggaaaccctg gagctgtcgg gaagcagatt 1320 ggagcagtga ggaagaacct ctgccctgtc agacaggact ttgagagcaa tgctgccctg 1380 ccacccttga caattatatg catttttctt agccttctgc ctcagaaatg tctcagtggt 1440 ccctcaaggt cttcgaatag atgtttatct aacctgacag ttgcagtttt cacccatgga 1500 aagcattagt ctgacagtac aatgtttgga ttctccttga tattaccaat acattttccc 1560 tgttatcttg cactgaatct ttcctactga acactttttc tgcacttttc attgtaataa 1620 aaggagttgc tgtccacaac cctaaaa 1647 <![CDATA[<210> 141]]> <![CDATA[<211> 875]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 141]]> Met Ala Ala Ala Thr Arg Arg Val Phe His Leu Gln Pro Cys Glu Asn 1 5 10 15 Ser Pro Thr Met Ser Gln Asn Gly Tyr Phe Glu Asp Ser Ser Tyr Tyr 20 25 30 Lys Cys Asp Thr Asp Asp Thr Phe Glu Ala Arg Glu Glu Ile Leu Gly 35 40 45 Asp Glu Ala Phe Asp Thr Ala Asn Ser Ser Ile Val Ser Gly Glu Ser 50 55 60 Ile Arg Phe Phe Val Asn Val Asn Leu Glu Met Gln Ala Thr Asn Thr 65 70 75 80 Glu Asn Glu Ala Thr Ser Gly Gly Cys Val Leu Leu His Thr Ser Arg 85 90 95 Lys Tyr Leu Lys Leu Lys Asn Phe Lys Glu Glu Ile Arg Ala His Arg 100 105 110 Asp Leu Asp Gly Phe Leu Ala Gln Ala Ser Ile Val Leu Asn Glu Thr 115 120 125 Ala Thr Ser Leu Asp Asn Val Leu Arg Thr Met Leu Arg Arg Phe Ala 130 135 140 Arg Asp Pro Asp Asn Asn Glu Pro Asn Cys Asn Leu Asp Leu Leu Met 145 150 155 160 Ala Met Leu Phe Thr Asp Ala Gly Ala Pro Met Arg Gly Lys Val His 165 170 175 Leu Leu Ser Asp Thr Ile Gln Gly Val Thr Ala Thr Val Thr Gly Val 180 185 190 Arg Tyr Gln Gln Ser Trp Leu Cys Ile Ile Cys Thr Met Lys Ala Leu 195 200 205 Gln Lys Arg His Val Cys Ile Ser Arg Leu Val Arg Pro Gln Asn Trp 210 215 220 Gly Glu Asn Ser Cys Glu Val Arg Phe Val Ile Leu Val Leu Ala Pro 225 230 235 240 Pro Lys Met Lys Ser Thr Lys Thr Ala Met Glu Val Ala Arg Thr Phe 245 250 255 Ala Thr Met Phe Ser Asp Ile Ala Phe Arg Gln Lys Leu Leu Glu Thr 260 265 270 Arg Thr Glu Glu Glu Phe Lys Glu Ala Leu Val His Gln Arg Gln Leu 275 280 285 Leu Thr Met Val Ser His Gly Pro Val Ala Pro Arg Thr Lys Glu Arg 290 295 300 Ser Thr Val Ser Leu Pro Ala His Arg His Pro Glu Pro Pro Lys Cys 305 310 315 320 Lys Asp Phe Val Pro Phe Gly Lys Gly Ile Arg Glu Asp Ile Ala Arg 325 330 335 Arg Phe Pro Leu Tyr Pro Leu Asp Phe Thr Asp Gly Ile Ile Gly Lys 340 345 350 Asn Lys Ala Val Gly Lys Tyr Ile Thr Thr Thr Leu Phe Leu Tyr Phe 355 360 365 Ala Cys Leu Leu Pro Thr Ile Ala Phe Gly Ser Leu Asn Asp Glu Asn 370 375 380 Thr Asp Gly Ala Ile Asp Val Gln Lys Thr Ile Ala Gly Gln Ser Ile 385 390 395 400 Gly Gly Leu Leu Tyr Ala Leu Phe Ser Gly Gln Pro Leu Val Ile Leu 405 410 415 Leu Thr Thr Ala Pro Leu Ala Leu Tyr Ile Gln Val Ile Arg Val Ile 420 425 430 Cys Asp Asp Tyr Asp Leu Asp Phe Asn Ser Phe Tyr Ala Trp Thr Gly 435 440 445 Leu Trp Asn Ser Phe Phe Leu Ala Leu Tyr Ala Phe Phe Asn Leu Ser 450 455 460 Leu Val Met Ser Leu Phe Lys Arg Ser Thr Glu Glu Ile Ile Ala Leu 465 470 475 480 Phe Ile Ser Ile Thr Phe Val Leu Asp Ala Val Lys Gly Thr Val Lys 485 490 495 Ile Phe Trp Lys Tyr Tyr Tyr Gly His Tyr Leu Asp Asp Tyr His Thr 500 505 510 Lys Arg Thr Ser Ser Leu Val Ser Leu Ser Gly Leu Gly Ala Ser Leu 515 520 525 Asn Ala Ser Leu His Thr Ala Leu Asn Ala Ser Phe Leu Ala Ser Pro 530 535 540 Thr Glu Leu Pro Ser Ala Thr His Ser Gly Gln Ala Thr Ala Val Leu 545 550 555 560 Ser Leu Leu Ile Met Leu Gly Thr Leu Trp Leu Gly Tyr Thr Leu Tyr 565 570 575 Gln Phe Lys Lys Ser Pro Tyr Leu His Pro Cys Val Arg Glu Ile Leu 580 585 590 Ser Asp Cys Ala Leu Pro Ile Ala Val Leu Ala Phe Ser Leu Ile Ser 595 600 605 Ser His Gly Phe Arg Glu Ile Glu Met Ser Lys Phe Arg Tyr Asn Pro 610 615 620 Ser Glu Ser Pro Phe Ala Met Ala Gln Ile Gln Ser Leu Ser Leu Arg 625 630 635 640 Ala Val Ser Gly Ala Met Gly Leu Gly Phe Leu Leu Ser Met Leu Phe 645 650 655 Phe Ile Glu Gln Asn Leu Val Ala Ala Leu Val Asn Ala Pro Glu Asn 660 665 670 Arg Leu Val Lys Gly Thr Ala Tyr His Trp Asp Leu Leu Leu Leu Ala 675 680 685 Ile Ile Asn Thr Gly Leu Ser Leu Phe Gly Leu Pro Trp Ile His Ala 690 695 700 Ala Tyr Pro His Ser Pro Leu His Val Arg Ala Leu Ala Leu Val Glu 705 710 715 720 Glu Arg Val Glu Asn Gly His Ile Tyr Asp Thr Ile Val Asn Val Lys 725 730 735 Glu Thr Arg Leu Thr Ser Leu Gly Ala Ser Val Leu Val Gly Leu Ser 740 745 750 Leu Leu Leu Leu Pro Val Pro Leu Gln Trp Ile Pro Lys Pro Val Leu 755 760 765 Tyr Gly Leu Phe Leu Tyr Ile Ala Leu Thr Ser Leu Asp Gly Asn Gln 770 775 780 Leu Val Gln Arg Val Ala Leu Leu Leu Lys Glu Gln Thr Ala Tyr Pro 785 790 795 800 Pro Thr His Tyr Ile Arg Arg Val Pro Gln Arg Lys Ile His Tyr Phe 805 810 815 Thr Gly Leu Gln Val Leu Gln Leu Leu Leu Leu Cys Ala Phe Gly Met 820 825 830 Ser Ser Leu Pro Tyr Met Lys Met Ile Phe Pro Leu Ile Met Ile Ala 835 840 845 Met Ile Pro Ile Arg Tyr Ile Leu Leu Pro Arg Ile Ile Glu Ala Lys 850 855 860 Tyr Leu Asp Val Met Asp Ala Glu His Arg Pro 865 870 875 <![CDATA[<210> 142]]> <![CDATA[<211> 891]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 142]]> Met Ser Gln Val Gly Gly Arg Gly Asp Arg Cys Thr Gln Glu Val Gln 1 5 10 15 Gly Leu Val His Gly Ala Gly Asp Leu Ser Ala Ser Leu Ala Glu Asn 20 25 30 Ser Pro Thr Met Ser Gln Asn Gly Tyr Phe Glu Asp Ser Ser Tyr Tyr 35 40 45 Lys Cys Asp Thr Asp Asp Thr Phe Glu Ala Arg Glu Glu Ile Leu Gly 50 55 60 Asp Glu Ala Phe Asp Thr Ala Asn Ser Ser Ile Val Ser Gly Glu Ser 65 70 75 80 Ile Arg Phe Phe Val Asn Val Asn Leu Glu Met Gln Ala Thr Asn Thr 85 90 95 Glu Asn Glu Ala Thr Ser Gly Gly Cys Val Leu Leu His Thr Ser Arg 100 105 110 Lys Tyr Leu Lys Leu Lys Asn Phe Lys Glu Glu Ile Arg Ala His Arg 115 120 125 Asp Leu Asp Gly Phe Leu Ala Gln Ala Ser Ile Val Leu Asn Glu Thr 130 135 140 Ala Thr Ser Leu Asp Asn Val Leu Arg Thr Met Leu Arg Arg Phe Ala 145 150 155 160 Arg Asp Pro Asp Asn Asn Glu Pro Asn Cys Asn Leu Asp Leu Leu Met 165 170 175 Ala Met Leu Phe Thr Asp Ala Gly Ala Pro Met Arg Gly Lys Val His 180 185 190 Leu Leu Ser Asp Thr Ile Gln Gly Val Thr Ala Thr Val Thr Gly Val 195 200 205 Arg Tyr Gln Gln Ser Trp Leu Cys Ile Ile Cys Thr Met Lys Ala Leu 210 215 220 Gln Lys Arg His Val Cys Ile Ser Arg Leu Val Arg Pro Gln Asn Trp 225 230 235 240 Gly Glu Asn Ser Cys Glu Val Arg Phe Val Ile Leu Val Leu Ala Pro 245 250 255 Pro Lys Met Lys Ser Thr Lys Thr Ala Met Glu Val Ala Arg Thr Phe 260 265 270 Ala Thr Met Phe Ser Asp Ile Ala Phe Arg Gln Lys Leu Leu Glu Thr 275 280 285 Arg Thr Glu Glu Glu Phe Lys Glu Ala Leu Val His Gln Arg Gln Leu 290 295 300 Leu Thr Met Val Ser His Gly Pro Val Ala Pro Arg Thr Lys Glu Arg 305 310 315 320 Ser Thr Val Ser Leu Pro Ala His Arg His Pro Glu Pro Pro Lys Cys 325 330 335 Lys Asp Phe Val Pro Phe Gly Lys Gly Ile Arg Glu Asp Ile Ala Arg 340 345 350 Arg Phe Pro Leu Tyr Pro Leu Asp Phe Thr Asp Gly Ile Ile Gly Lys 355 360 365 Asn Lys Ala Val Gly Lys Tyr Ile Thr Thr Thr Leu Phe Leu Tyr Phe 370 375 380 Ala Cys Leu Leu Pro Thr Ile Ala Phe Gly Ser Leu Asn Asp Glu Asn 385 390 395 400 Thr Asp Gly Ala Ile Asp Val Gln Lys Thr Ile Ala Gly Gln Ser Ile 405 410 415 Gly Gly Leu Leu Tyr Ala Leu Phe Ser Gly Gln Pro Leu Val Ile Leu 420 425 430 Leu Thr Thr Ala Pro Leu Ala Leu Tyr Ile Gln Val Ile Arg Val Ile 435 440 445 Cys Asp Asp Tyr Asp Leu Asp Phe Asn Ser Phe Tyr Ala Trp Thr Gly 450 455 460 Leu Trp Asn Ser Phe Phe Leu Ala Leu Tyr Ala Phe Phe Asn Leu Ser 465 470 475 480 Leu Val Met Ser Leu Phe Lys Arg Ser Thr Glu Glu Ile Ile Ala Leu 485 490 495 Phe Ile Ser Ile Thr Phe Val Leu Asp Ala Val Lys Gly Thr Val Lys 500 505 510 Ile Phe Trp Lys Tyr Tyr Tyr Gly His Tyr Leu Asp Asp Tyr His Thr 515 520 525 Lys Arg Thr Ser Ser Leu Val Ser Leu Ser Gly Leu Gly Ala Ser Leu 530 535 540 Asn Ala Ser Leu His Thr Ala Leu Asn Ala Ser Phe Leu Ala Ser Pro 545 550 555 560 Thr Glu Leu Pro Ser Ala Thr His Ser Gly Gln Ala Thr Ala Val Leu 565 570 575 Ser Leu Leu Ile Met Leu Gly Thr Leu Trp Leu Gly Tyr Thr Leu Tyr 580 585 590 Gln Phe Lys Lys Ser Pro Tyr Leu His Pro Cys Val Arg Glu Ile Leu 595 600 605 Ser Asp Cys Ala Leu Pro Ile Ala Val Leu Ala Phe Ser Leu Ile Ser 610 615 620 Ser His Gly Phe Arg Glu Ile Glu Met Ser Lys Phe Arg Tyr Asn Pro 625 630 635 640 Ser Glu Ser Pro Phe Ala Met Ala Gln Ile Gln Ser Leu Ser Leu Arg 645 650 655 Ala Val Ser Gly Ala Met Gly Leu Gly Phe Leu Leu Ser Met Leu Phe 660 665 670 Phe Ile Glu Gln Asn Leu Val Ala Ala Leu Val Asn Ala Pro Glu Asn 675 680 685 Arg Leu Val Lys Gly Thr Ala Tyr His Trp Asp Leu Leu Leu Leu Ala 690 695 700 Ile Ile Asn Thr Gly Leu Ser Leu Phe Gly Leu Pro Trp Ile His Ala 705 710 715 720 Ala Tyr Pro His Ser Pro Leu His Val Arg Ala Leu Ala Leu Val Glu 725 730 735 Glu Arg Val Glu Asn Gly His Ile Tyr Asp Thr Ile Val Asn Val Lys 740 745 750 Glu Thr Arg Leu Thr Ser Leu Gly Ala Ser Val Leu Val Gly Leu Ser 755 760 765 Leu Leu Leu Leu Pro Val Pro Leu Gln Trp Ile Pro Lys Pro Val Leu 770 775 780 Tyr Gly Leu Phe Leu Tyr Ile Ala Leu Thr Ser Leu Asp Gly Asn Gln 785 790 795 800 Leu Val Gln Arg Val Ala Leu Leu Leu Lys Glu Gln Thr Ala Tyr Pro 805 810 815 Pro Thr His Tyr Ile Arg Arg Val Pro Gln Arg Lys Ile His Tyr Phe 820 825 830 Thr Gly Leu Gln Val Leu Gln Leu Leu Leu Leu Cys Ala Phe Gly Met 835 840 845 Ser Ser Leu Pro Tyr Met Lys Met Ile Phe Pro Leu Ile Met Ile Ala 850 855 860 Met Ile Pro Ile Arg Tyr Ile Leu Leu Pro Arg Ile Ile Glu Ala Lys 865 870 875 880 Tyr Leu Asp Val Met Asp Ala Glu His Arg Pro 885 890 <![CDATA[<210> 143]]> <![CDATA[<211> 918]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 143]]> Met Gly Val Tyr Gly Pro Gln Asp Arg Ser Glu Ser Glu Lys Arg Asp 1 5 10 15 Val Gln Arg Asp Pro Pro Pro Trp His Pro Arg Arg Glu Gly Glu Arg 20 25 30 Pro Ala Arg Ala Arg Ser Leu Pro Leu Ala Ala Ala Gly Gln Gly Phe 35 40 45 Leu Arg Lys Thr Trp Ile Ser Glu His Glu Asn Ser Pro Thr Met Ser 50 55 60 Gln Asn Gly Tyr Phe Glu Asp Ser Ser Tyr Tyr Lys Cys Asp Thr Asp 65 70 75 80 Asp Thr Phe Glu Ala Arg Glu Glu Ile Leu Gly Asp Glu Ala Phe Asp 85 90 95 Thr Ala Asn Ser Ser Ile Val Ser Gly Glu Ser Ile Arg Phe Phe Val 100 105 110 Asn Val Asn Leu Glu Met Gln Ala Thr Asn Thr Glu Asn Glu Ala Thr 115 120 125 Ser Gly Gly Cys Val Leu Leu His Thr Ser Arg Lys Tyr Leu Lys Leu 130 135 140 Lys Asn Phe Lys Glu Glu Ile Arg Ala His Arg Asp Leu Asp Gly Phe 145 150 155 160 Leu Ala Gln Ala Ser Ile Val Leu Asn Glu Thr Ala Thr Ser Leu Asp 165 170 175 Asn Val Leu Arg Thr Met Leu Arg Arg Phe Ala Arg Asp Pro Asp Asn 180 185 190 Asn Glu Pro Asn Cys Asn Leu Asp Leu Leu Met Ala Met Leu Phe Thr 195 200 205 Asp Ala Gly Ala Pro Met Arg Gly Lys Val His Leu Leu Ser Asp Thr 210 215 220 Ile Gln Gly Val Thr Ala Thr Val Thr Gly Val Arg Tyr Gln Gln Ser 225 230 235 240 Trp Leu Cys Ile Ile Cys Thr Met Lys Ala Leu Gln Lys Arg His Val 245 250 255 Cys Ile Ser Arg Leu Val Arg Pro Gln Asn Trp Gly Glu Asn Ser Cys 260 265 270 Glu Val Arg Phe Val Ile Leu Val Leu Ala Pro Pro Lys Met Lys Ser 275 280 285 Thr Lys Thr Ala Met Glu Val Ala Arg Thr Phe Ala Thr Met Phe Ser 290 295 300 Asp Ile Ala Phe Arg Gln Lys Leu Leu Glu Thr Arg Thr Glu Glu Glu 305 310 315 320 Phe Lys Glu Ala Leu Val His Gln Arg Gln Leu Leu Thr Met Val Ser 325 330 335 His Gly Pro Val Ala Pro Arg Thr Lys Glu Arg Ser Thr Val Ser Leu 340 345 350 Pro Ala His Arg His Pro Glu Pro Pro Lys Cys Lys Asp Phe Val Pro 355 360 365 Phe Gly Lys Gly Ile Arg Glu Asp Ile Ala Arg Arg Phe Pro Leu Tyr 370 375 380 Pro Leu Asp Phe Thr Asp Gly Ile Ile Gly Lys Asn Lys Ala Val Gly 385 390 395 400 Lys Tyr Ile Thr Thr Thr Leu Phe Leu Tyr Phe Ala Cys Leu Leu Pro 405 410 415 Thr Ile Ala Phe Gly Ser Leu Asn Asp Glu Asn Thr Asp Gly Ala Ile 420 425 430 Asp Val Gln Lys Thr Ile Ala Gly Gln Ser Ile Gly Gly Leu Leu Tyr 435 440 445 Ala Leu Phe Ser Gly Gln Pro Leu Val Ile Leu Leu Thr Thr Ala Pro 450 455 460 Leu Ala Leu Tyr Ile Gln Val Ile Arg Val Ile Cys Asp Asp Tyr Asp 465 470 475 480 Leu Asp Phe Asn Ser Phe Tyr Ala Trp Thr Gly Leu Trp Asn Ser Phe 485 490 495 Phe Leu Ala Leu Tyr Ala Phe Phe Asn Leu Ser Leu Val Met Ser Leu 500 505 510 Phe Lys Arg Ser Thr Glu Glu Ile Ile Ala Leu Phe Ile Ser Ile Thr 515 520 525 Phe Val Leu Asp Ala Val Lys Gly Thr Val Lys Ile Phe Trp Lys Tyr 530 535 540 Tyr Tyr Gly His Tyr Leu Asp Asp Tyr His Thr Lys Arg Thr Ser Ser 545 550 555 560 Leu Val Ser Leu Ser Gly Leu Gly Ala Ser Leu Asn Ala Ser Leu His 565 570 575 Thr Ala Leu Asn Ala Ser Phe Leu Ala Ser Pro Thr Glu Leu Pro Ser 580 585 590 Ala Thr His Ser Gly Gln Ala Thr Ala Val Leu Ser Leu Leu Ile Met 595 600 605 Leu Gly Thr Leu Trp Leu Gly Tyr Thr Leu Tyr Gln Phe Lys Lys Ser 610 615 620 Pro Tyr Leu His Pro Cys Val Arg Glu Ile Leu Ser Asp Cys Ala Leu 625 630 635 640 Pro Ile Ala Val Leu Ala Phe Ser Leu Ile Ser Ser His Gly Phe Arg 645 650 655 Glu Ile Glu Met Ser Lys Phe Arg Tyr Asn Pro Ser Glu Ser Pro Phe 660 665 670 Ala Met Ala Gln Ile Gln Ser Leu Ser Leu Arg Ala Val Ser Gly Ala 675 680 685 Met Gly Leu Gly Phe Leu Leu Ser Met Leu Phe Phe Ile Glu Gln Asn 690 695 700 Leu Val Ala Ala Leu Val Asn Ala Pro Glu Asn Arg Leu Val Lys Gly 705 710 715 720 Thr Ala Tyr His Trp Asp Leu Leu Leu Leu Ala Ile Ile Asn Thr Gly 725 730 735 Leu Ser Leu Phe Gly Leu Pro Trp Ile His Ala Ala Tyr Pro His Ser 740 745 750 Pro Leu His Val Arg Ala Leu Ala Leu Val Glu Glu Arg Val Glu Asn 755 760 765 Gly His Ile Tyr Asp Thr Ile Val Asn Val Lys Glu Thr Arg Leu Thr 770 775 780 Ser Leu Gly Ala Ser Val Leu Val Gly Leu Ser Leu Leu Leu Leu Pro 785 790 795 800 Val Pro Leu Gln Trp Ile Pro Lys Pro Val Leu Tyr Gly Leu Phe Leu 805 810 815 Tyr Ile Ala Leu Thr Ser Leu Asp Gly Asn Gln Leu Val Gln Arg Val 820 825 830 Ala Leu Leu Leu Lys Glu Gln Thr Ala Tyr Pro Pro Thr His Tyr Ile 835 840 845 Arg Arg Val Pro Gln Arg Lys Ile His Tyr Phe Thr Gly Leu Gln Val 850 855 860 Leu Gln Leu Leu Leu Leu Cys Ala Phe Gly Met Ser Ser Leu Pro Tyr 865 870 875 880 Met Lys Met Ile Phe Pro Leu Ile Met Ile Ala Met Ile Pro Ile Arg 885 890 895 Tyr Ile Leu Leu Pro Arg Ile Ile Glu Ala Lys Tyr Leu Asp Val Met 900 905 910 Asp Ala Glu His Arg Pro 915 <![CDATA[<210> 144]]> <![CDATA[<211> 837]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 144]]> Met Ala Ala Ala Thr Arg Arg Val Phe His Leu Gln Pro Cys Glu Asn 1 5 10 15 Ser Pro Thr Met Ser Gln Asn Gly Tyr Phe Glu Asp Ser Ser Tyr Tyr 20 25 30 Lys Cys Asp Thr Asp Asp Thr Phe Glu Ala Arg Glu Glu Ile Leu Gly 35 40 45 Asp Glu Ala Phe Asp Thr Ala Asn Ser Ser Ile Val Ser Gly Glu Ser 50 55 60 Ile Arg Phe Phe Val Asn Val Asn Leu Glu Met Gln Ala Thr Asn Thr 65 70 75 80 Glu Asn Glu Ala Thr Ser Gly Gly Cys Val Leu Leu His Thr Ser Arg 85 90 95 Lys Tyr Leu Lys Leu Lys Asn Phe Lys Glu Glu Ile Arg Ala His Arg 100 105 110 Asp Leu Asp Gly Phe Leu Ala Gln Ala Ser Ile Val Leu Asn Glu Thr 115 120 125 Ala Thr Ser Leu Asp Asn Val Leu Arg Thr Met Leu Arg Arg Phe Ala 130 135 140 Arg Asp Pro Asp Asn Asn Glu Pro Asn Cys Asn Leu Asp Leu Leu Met 145 150 155 160 Ala Met Leu Phe Thr Asp Ala Gly Ala Pro Met Arg Gly Lys Val His 165 170 175 Leu Leu Ser Asp Thr Ile Gln Gly Val Thr Ala Thr Val Thr Gly Val 180 185 190 Arg Tyr Gln Gln Ser Trp Leu Cys Ile Ile Cys Thr Met Lys Ala Leu 195 200 205 Gln Lys Arg His Val Cys Ile Ser Arg Leu Val Arg Pro Gln Asn Trp 210 215 220 Gly Glu Asn Ser Cys Glu Val Arg Phe Val Ile Leu Val Leu Ala Pro 225 230 235 240 Pro Lys Met Lys Ser Thr Lys Thr Ala Met Glu Val Ala Arg Thr Phe 245 250 255 Ala Thr Met Phe Ser Asp Ile Ala Phe Arg Gln Lys Leu Leu Glu Thr 260 265 270 Arg Thr Glu Glu Glu Phe Lys Glu Ala Leu Val His Gln Arg Gln Leu 275 280 285 Leu Thr Met Val Ser His Gly Pro Val Ala Pro Arg Thr Lys Glu Arg 290 295 300 Ser Thr Val Ser Leu Pro Ala His Arg His Pro Glu Pro Pro Lys Cys 305 310 315 320 Lys Asp Phe Val Pro Phe Gly Lys Gly Ile Arg Glu Asp Ile Ala Arg 325 330 335 Arg Phe Pro Leu Tyr Pro Leu Asp Phe Thr Asp Gly Ile Ile Gly Lys 340 345 350 Asn Lys Ala Val Gly Lys Tyr Ile Thr Thr Thr Leu Phe Leu Tyr Phe 355 360 365 Ala Cys Leu Leu Pro Thr Ile Ala Phe Gly Ser Leu Asn Asp Glu Asn 370 375 380 Thr Asp Gly Ala Ile Val Ile Arg Val Ile Cys Asp Asp Tyr Asp Leu 385 390 395 400 Asp Phe Asn Ser Phe Tyr Ala Trp Thr Gly Leu Trp Asn Ser Phe Phe 405 410 415 Leu Ala Leu Tyr Ala Phe Phe Asn Leu Ser Leu Val Met Ser Leu Phe 420 425 430 Lys Arg Ser Thr Glu Glu Ile Ile Ala Leu Phe Ile Ser Ile Thr Phe 435 440 445 Val Leu Asp Ala Val Lys Gly Thr Val Lys Ile Phe Trp Lys Tyr Tyr 450 455 460 Tyr Gly His Tyr Leu Asp Asp Tyr His Thr Lys Arg Thr Ser Ser Leu 465 470 475 480 Val Ser Leu Ser Gly Leu Gly Ala Ser Leu Asn Ala Ser Leu His Thr 485 490 495 Ala Leu Asn Ala Ser Phe Leu Ala Ser Pro Thr Glu Leu Pro Ser Ala 500 505 510 Thr His Ser Gly Gln Ala Thr Ala Val Leu Ser Leu Leu Ile Met Leu 515 520 525 Gly Thr Leu Trp Leu Gly Tyr Thr Leu Tyr Gln Phe Lys Lys Ser Pro 530 535 540 Tyr Leu His Pro Cys Val Arg Glu Ile Leu Ser Asp Cys Ala Leu Pro 545 550 555 560 Ile Ala Val Leu Ala Phe Ser Leu Ile Ser Ser His Gly Phe Arg Glu 565 570 575 Ile Glu Met Ser Lys Phe Arg Tyr Asn Pro Ser Glu Ser Pro Phe Ala 580 585 590 Met Ala Gln Ile Gln Ser Leu Ser Leu Arg Ala Val Ser Gly Ala Met 595 600 605 Gly Leu Gly Phe Leu Leu Ser Met Leu Phe Phe Ile Glu Gln Asn Leu 610 615 620 Val Ala Ala Leu Val Asn Ala Pro Glu Asn Arg Leu Val Lys Gly Thr 625 630 635 640 Ala Tyr His Trp Asp Leu Leu Leu Leu Ala Ile Ile Asn Thr Gly Leu 645 650 655 Ser Leu Phe Gly Leu Pro Trp Ile His Ala Ala Tyr Pro His Ser Pro 660 665 670 Leu His Val Arg Ala Leu Ala Leu Val Glu Glu Arg Val Glu Asn Gly 675 680 685 His Ile Tyr Asp Thr Ile Val Asn Val Lys Glu Thr Arg Leu Thr Ser 690 695 700 Leu Gly Ala Ser Val Leu Val Gly Leu Ser Leu Leu Leu Leu Pro Val 705 710 715 720 Pro Leu Gln Trp Ile Pro Lys Pro Val Leu Tyr Gly Leu Phe Leu Tyr 725 730 735 Ile Ala Leu Thr Ser Leu Asp Gly Asn Gln Leu Val Gln Arg Val Ala 740 745 750 Leu Leu Leu Lys Glu Gln Thr Ala Tyr Pro Pro Thr His Tyr Ile Arg 755 760 765 Arg Val Pro Gln Arg Lys Ile His Tyr Phe Thr Gly Leu Gln Val Leu 770 775 780 Gln Leu Leu Leu Leu Cys Ala Phe Gly Met Ser Ser Leu Pro Tyr Met 785 790 795 800 Lys Met Ile Phe Pro Leu Ile Met Ile Ala Met Ile Pro Ile Arg Tyr 805 810 815 Ile Leu Leu Pro Arg Ile Ile Glu Ala Lys Tyr Leu Asp Val Met Asp 820 825 830 Ala Glu His Arg Pro 835 <![CDATA[<210> 145]]> <![CDATA[<211> 744]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 145]]> Met Ala Val Leu Pro Gly Pro Leu Gln Leu Leu Gly Val Leu Leu Thr 1 5 10 15 Ile Ser Leu Ser Ser Ile Arg Leu Ile Gln Ala Gly Ala Tyr Tyr Gly 20 25 30 Ile Lys Pro Leu Pro Pro Gln Ile Pro Pro Gln Met Pro Pro Gln Ile 35 40 45 Pro Gln Tyr Gln Pro Leu Gly Gln Gln Val Pro His Met Pro Leu Ala 50 55 60 Lys Asp Gly Leu Ala Met Gly Lys Glu Met Pro His Leu Gln Tyr Gly 65 70 75 80 Lys Glu Tyr Pro His Leu Pro Gln Tyr Met Lys Glu Ile Gln Pro Ala 85 90 95 Pro Arg Met Gly Lys Glu Ala Val Pro Lys Lys Gly Lys Glu Ile Pro 100 105 110 Leu Ala Ser Leu Arg Gly Glu Gln Gly Pro Arg Gly Glu Pro Gly Pro 115 120 125 Arg Gly Pro Pro Gly Pro Pro Gly Leu Pro Gly His Gly Ile Pro Gly 130 135 140 Ile Lys Gly Lys Pro Gly Pro Gln Gly Tyr Pro Gly Val Gly Lys Pro 145 150 155 160 Gly Met Pro Gly Met Pro Gly Lys Pro Gly Ala Met Gly Met Pro Gly 165 170 175 Ala Lys Gly Glu Ile Gly Gln Lys Gly Glu Ile Gly Pro Met Gly Ile 180 185 190 Pro Gly Pro Gln Gly Pro Pro Gly Pro His Gly Leu Pro Gly Ile Gly 195 200 205 Lys Pro Gly Gly Pro Gly Leu Pro Gly Gln Pro Gly Pro Lys Gly Asp 210 215 220 Arg Gly Pro Lys Gly Leu Pro Gly Pro Gln Gly Leu Arg Gly Pro Lys 225 230 235 240 Gly Asp Lys Gly Phe Gly Met Pro Gly Ala Pro Gly Val Lys Gly Pro 245 250 255 Pro Gly Met His Gly Pro Pro Gly Pro Val Gly Leu Pro Gly Val Gly 260 265 270 Lys Pro Gly Val Thr Gly Phe Pro Gly Pro Gln Gly Pro Leu Gly Lys 275 280 285 Pro Gly Ala Pro Gly Glu Pro Gly Pro Gln Gly Pro Ile Gly Val Pro 290 295 300 Gly Val Gln Gly Pro Pro Gly Ile Pro Gly Ile Gly Lys Pro Gly Gln 305 310 315 320 Asp Gly Ile Pro Gly Gln Pro Gly Phe Pro Gly Gly Lys Gly Glu Gln 325 330 335 Gly Leu Pro Gly Leu Pro Gly Pro Pro Gly Leu Pro Gly Ile Gly Lys 340 345 350 Pro Gly Phe Pro Gly Pro Lys Gly Asp Arg Gly Met Gly Gly Val Pro 355 360 365 Gly Ala Leu Gly Pro Arg Gly Glu Lys Gly Pro Ile Gly Ala Pro Gly 370 375 380 Ile Gly Gly Pro Pro Gly Glu Pro Gly Leu Pro Gly Ile Pro Gly Pro 385 390 395 400 Met Gly Pro Pro Gly Ala Ile Gly Phe Pro Gly Pro Lys Gly Glu Gly 405 410 415 Gly Ile Val Gly Pro Gln Gly Pro Pro Gly Pro Lys Gly Glu Pro Gly 420 425 430 Leu Gln Gly Phe Pro Gly Lys Pro Gly Phe Leu Gly Glu Val Gly Pro 435 440 445 Pro Gly Met Arg Gly Leu Pro Gly Pro Ile Gly Pro Lys Gly Glu Ala 450 455 460 Gly Gln Lys Gly Val Pro Gly Leu Pro Gly Val Pro Gly Leu Leu Gly 465 470 475 480 Pro Lys Gly Glu Pro Gly Ile Pro Gly Asp Gln Gly Leu Gln Gly Pro 485 490 495 Pro Gly Ile Pro Gly Ile Gly Gly Pro Ser Gly Pro Ile Gly Pro Pro 500 505 510 Gly Ile Pro Gly Pro Lys Gly Glu Pro Gly Leu Pro Gly Pro Pro Gly 515 520 525 Phe Pro Gly Ile Gly Lys Pro Gly Val Ala Gly Leu His Gly Pro Pro 530 535 540 Gly Lys Pro Gly Ala Leu Gly Pro Gln Gly Gln Pro Gly Leu Pro Gly 545 550 555 560 Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Ala Val Met Pro Pro 565 570 575 Thr Pro Pro Pro Gln Gly Glu Tyr Leu Pro Asp Met Gly Leu Gly Ile 580 585 590 Asp Gly Val Lys Pro Pro His Ala Tyr Gly Ala Lys Lys Gly Lys Asn 595 600 605 Gly Gly Pro Ala Tyr Glu Met Pro Ala Phe Thr Ala Glu Leu Thr Ala 610 615 620 Pro Phe Pro Pro Val Gly Ala Pro Val Lys Phe Asn Lys Leu Leu Tyr 625 630 635 640 Asn Gly Arg Gln Asn Tyr Asn Pro Gln Thr Gly Ile Phe Thr Cys Glu 645 650 655 Val Pro Gly Val Tyr Tyr Phe Ala Tyr His Val His Cys Lys Gly Gly 660 665 670 Asn Val Trp Val Ala Leu Phe Lys Asn Asn Glu Pro Val Met Tyr Thr 675 680 685 Tyr Asp Glu Tyr Lys Lys Gly Phe Leu Asp Gln Ala Ser Gly Ser Ala 690 695 700 Val Leu Leu Leu Arg Pro Gly Asp Arg Val Phe Leu Gln Met Pro Ser 705 710 715 720 Glu Gln Ala Ala Gly Leu Tyr Ala Gly Gln Tyr Val His Ser Ser Phe 725 730 735 Ser Gly Tyr Leu Leu Tyr Pro Met 740 <![CDATA[<210> 146]]> <![CDATA[<211> 322]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 146]]> Met Asp Ser Thr Ile Pro Val Leu Gly Thr Glu Leu Thr Pro Ile Asn 1 5 10 15 Gly Arg Glu Glu Thr Pro Cys Tyr Lys Gln Thr Leu Ser Phe Thr Gly 20 25 30 Leu Thr Cys Ile Val Ser Leu Val Ala Leu Thr Gly Asn Ala Val Val 35 40 45 Leu Trp Leu Leu Gly Cys Arg Met Arg Arg Asn Ala Val Ser Ile Tyr 50 55 60 Ile Leu Asn Leu Val Ala Ala Asp Phe Leu Phe Leu Ser Gly His Ile 65 70 75 80 Ile Cys Ser Pro Leu Arg Leu Ile Asn Ile Arg His Pro Ile Ser Lys 85 90 95 Ile Leu Ser Pro Val Met Thr Phe Pro Tyr Phe Ile Gly Leu Ser Met 100 105 110 Leu Ser Ala Ile Ser Thr Glu Arg Cys Leu Ser Ile Leu Trp Pro Ile 115 120 125 Trp Tyr His Cys Arg Arg Pro Arg Tyr Leu Ser Ser Val Met Cys Val 130 135 140 Leu Leu Trp Ala Leu Ser Leu Leu Arg Ser Ile Leu Glu Trp Met Phe 145 150 155 160 Cys Asp Phe Leu Phe Ser Gly Ala Asn Ser Val Trp Cys Glu Thr Ser 165 170 175 Asp Phe Ile Thr Ile Ala Trp Leu Val Phe Leu Cys Val Val Leu Cys 180 185 190 Gly Ser Ser Leu Val Leu Leu Val Arg Ile Leu Cys Gly Ser Arg Lys 195 200 205 Met Pro Leu Thr Arg Leu Tyr Val Thr Ile Leu Leu Thr Val Leu Val 210 215 220 Phe Leu Leu Cys Gly Leu Pro Phe Gly Ile Gln Trp Ala Leu Phe Ser 225 230 235 240 Arg Ile His Leu Asp Trp Lys Val Leu Phe Cys His Val His Leu Val 245 250 255 Ser Ile Phe Leu Ser Ala Leu Asn Ser Ser Ala Asn Pro Ile Ile Tyr 260 265 270 Phe Phe Val Gly Ser Phe Arg Gln Arg Gln Asn Arg Gln Asn Leu Lys 275 280 285 Leu Val Leu Gln Arg Ala Leu Gln Asp Thr Pro Glu Val Asp Glu Gly 290 295 300 Gly Gly Trp Leu Pro Gln Glu Thr Leu Glu Leu Ser Gly Ser Arg Leu 305 310 315 320 Glu Gln <![CDATA[<210> 147]]> <![CDATA[<211> 638]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 147]]> Met Pro Leu Pro Leu Leu Pro Met Asp Leu Lys Gly Glu Pro Gly Pro 1 5 10 15 Pro Gly Lys Pro Gly Pro Arg Gly Pro Pro Gly Pro Pro Gly Phe Pro 20 25 30 Gly Lys Pro Gly Met Gly Lys Pro Gly Leu His Gly Gln Pro Gly Pro 35 40 45 Ala Gly Pro Pro Gly Phe Ser Arg Met Gly Lys Ala Gly Pro Pro Gly 50 55 60 Leu Pro Gly Lys Val Gly Pro Pro Gly Gln Pro Gly Leu Arg Gly Glu 65 70 75 80 Pro Gly Ile Arg Gly Asp Gln Gly Leu Arg Gly Pro Pro Gly Pro Pro 85 90 95 Gly Leu Pro Gly Pro Ser Gly Ile Thr Ile Pro Gly Lys Pro Gly Ala 100 105 110 Gln Gly Val Pro Gly Pro Pro Gly Phe Gln Gly Glu Pro Gly Pro Gln 115 120 125 Gly Glu Pro Gly Pro Pro Gly Asp Arg Gly Leu Lys Gly Asp Asn Gly 130 135 140 Val Gly Gln Pro Gly Leu Pro Gly Ala Pro Gly Gln Gly Gly Ala Pro 145 150 155 160 Gly Pro Pro Gly Leu Pro Gly Pro Ala Gly Leu Gly Lys Pro Gly Leu 165 170 175 Asp Gly Leu Pro Gly Ala Pro Gly Asp Lys Gly Glu Ser Gly Pro Pro 180 185 190 Gly Val Pro Gly Pro Arg Gly Glu Pro Gly Ala Val Gly Pro Lys Gly 195 200 205 Pro Pro Gly Val Asp Gly Val Gly Val Pro Gly Ala Ala Gly Leu Pro 210 215 220 Gly Pro Gln Gly Pro Ser Gly Ala Lys Gly Glu Pro Gly Thr Arg Gly 225 230 235 240 Pro Pro Gly Leu Ile Gly Pro Thr Gly Tyr Gly Met Pro Gly Leu Pro 245 250 255 Gly Pro Lys Gly Asp Arg Gly Pro Ala Gly Val Pro Gly Leu Leu Gly 260 265 270 Asp Arg Gly Glu Pro Gly Glu Asp Gly Glu Pro Gly Glu Gln Gly Pro 275 280 285 Gln Gly Leu Gly Gly Pro Pro Gly Leu Pro Gly Ser Ala Gly Leu Pro 290 295 300 Gly Arg Arg Gly Pro Pro Gly Pro Lys Gly Glu Ala Gly Pro Gly Gly 305 310 315 320 Pro Pro Gly Val Pro Gly Ile Arg Gly Asp Gln Gly Pro Ser Gly Leu 325 330 335 Ala Gly Lys Pro Gly Val Pro Gly Glu Arg Gly Leu Pro Gly Ala His 340 345 350 Gly Pro Pro Gly Pro Thr Gly Pro Lys Gly Glu Pro Gly Phe Thr Gly 355 360 365 Arg Pro Gly Gly Pro Gly Val Ala Gly Ala Leu Gly Gln Lys Gly Asp 370 375 380 Leu Gly Leu Pro Gly Gln Pro Gly Leu Arg Gly Pro Ser Gly Ile Pro 385 390 395 400 Gly Leu Gln Gly Pro Ala Gly Pro Ile Gly Pro Gln Gly Leu Pro Gly 405 410 415 Leu Lys Gly Glu Pro Gly Leu Pro Gly Pro Pro Gly Glu Gly Arg Ala 420 425 430 Gly Glu Pro Gly Thr Ala Gly Pro Thr Gly Pro Pro Gly Val Pro Gly 435 440 445 Ser Pro Gly Ile Thr Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro 450 455 460 Pro Gly Ala Pro Gly Ala Phe Asp Glu Thr Gly Ile Ala Gly Leu His 465 470 475 480 Leu Pro Asn Gly Gly Val Glu Gly Ala Val Leu Gly Lys Gly Gly Lys 485 490 495 Pro Gln Phe Gly Leu Gly Glu Leu Ser Ala His Ala Thr Pro Ala Phe 500 505 510 Thr Ala Val Leu Thr Ser Pro Phe Pro Ala Ser Gly Met Pro Val Lys 515 520 525 Phe Asp Arg Thr Leu Tyr Asn Gly His Ser Gly Tyr Asn Pro Ala Thr 530 535 540 Gly Ile Phe Thr Cys Pro Val Gly Gly Val Tyr Tyr Phe Ala Tyr His 545 550 555 560 Val His Val Lys Gly Thr Asn Val Trp Val Ala Leu Tyr Lys Asn Asn 565 570 575 Val Pro Ala Thr Tyr Thr Tyr Asp Glu Tyr Lys Lys Gly Tyr Leu Asp 580 585 590 Gln Ala Ser Gly Gly Ala Val Leu Gln Leu Arg Pro Asn Asp Gln Val 595 600 605 Trp Val Gln Met Pro Ser Asp Gln Ala Asn Gly Leu Tyr Ser Thr Glu 610 615 620 Tyr Ile His Ser Ser Phe Ser Gly Phe Leu Leu Cys Pro Thr 625 630 635 <![CDATA[<210> 148]]> <![CDATA[<211> 703]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 148]]> Met Leu Gly Thr Leu Thr Pro Leu Ser Ser Leu Leu Leu Leu Leu Leu 1 5 10 15 Val Leu Val Leu Gly Cys Gly Pro Arg Ala Ser Ser Gly Gly Gly Ala 20 25 30 Gly Gly Ala Ala Gly Tyr Ala Pro Val Lys Tyr Ile Gln Pro Met Gln 35 40 45 Lys Gly Pro Val Gly Pro Pro Phe Arg Glu Gly Lys Gly Gln Tyr Leu 50 55 60 Glu Met Pro Leu Pro Leu Leu Pro Met Asp Leu Lys Gly Glu Pro Gly 65 70 75 80 Pro Pro Gly Lys Pro Gly Pro Arg Gly Pro Pro Gly Pro Pro Gly Phe 85 90 95 Pro Gly Lys Pro Gly Met Gly Lys Pro Gly Leu His Gly Gln Pro Gly 100 105 110 Pro Ala Gly Pro Pro Gly Phe Ser Arg Met Gly Lys Ala Gly Pro Pro 115 120 125 Gly Leu Pro Gly Lys Val Gly Pro Pro Gly Gln Pro Gly Leu Arg Gly 130 135 140 Glu Pro Gly Ile Arg Gly Asp Gln Gly Leu Arg Gly Pro Pro Gly Pro 145 150 155 160 Pro Gly Leu Pro Gly Pro Ser Gly Ile Thr Ile Pro Gly Lys Pro Gly 165 170 175 Ala Gln Gly Val Pro Gly Pro Pro Gly Phe Gln Gly Glu Pro Gly Pro 180 185 190 Gln Gly Glu Pro Gly Pro Pro Gly Asp Arg Gly Leu Lys Gly Asp Asn 195 200 205 Gly Val Gly Gln Pro Gly Leu Pro Gly Ala Pro Gly Gln Gly Gly Ala 210 215 220 Pro Gly Pro Pro Gly Leu Pro Gly Pro Ala Gly Leu Gly Lys Pro Gly 225 230 235 240 Leu Asp Gly Leu Pro Gly Ala Pro Gly Asp Lys Gly Glu Ser Gly Pro 245 250 255 Pro Gly Val Pro Gly Pro Arg Gly Glu Pro Gly Ala Val Gly Pro Lys 260 265 270 Gly Pro Pro Gly Val Asp Gly Val Gly Val Pro Gly Ala Ala Gly Leu 275 280 285 Pro Gly Pro Gln Gly Pro Ser Gly Ala Lys Gly Glu Pro Gly Thr Arg 290 295 300 Gly Pro Pro Gly Leu Ile Gly Pro Thr Gly Tyr Gly Met Pro Gly Leu 305 310 315 320 Pro Gly Pro Lys Gly Asp Arg Gly Pro Ala Gly Val Pro Gly Leu Leu 325 330 335 Gly Asp Arg Gly Glu Pro Gly Glu Asp Gly Glu Pro Gly Glu Gln Gly 340 345 350 Pro Gln Gly Leu Gly Gly Pro Pro Gly Leu Pro Gly Ser Ala Gly Leu 355 360 365 Pro Gly Arg Arg Gly Pro Pro Gly Pro Lys Gly Glu Ala Gly Pro Gly 370 375 380 Gly Pro Pro Gly Val Pro Gly Ile Arg Gly Asp Gln Gly Pro Ser Gly 385 390 395 400 Leu Ala Gly Lys Pro Gly Val Pro Gly Glu Arg Gly Leu Pro Gly Ala 405 410 415 His Gly Pro Pro Gly Pro Thr Gly Pro Lys Gly Glu Pro Gly Phe Thr 420 425 430 Gly Arg Pro Gly Gly Pro Gly Val Ala Gly Ala Leu Gly Gln Lys Gly 435 440 445 Asp Leu Gly Leu Pro Gly Gln Pro Gly Leu Arg Gly Pro Ser Gly Ile 450 455 460 Pro Gly Leu Gln Gly Pro Ala Gly Pro Ile Gly Pro Gln Gly Leu Pro 465 470 475 480 Gly Leu Lys Gly Glu Pro Gly Leu Pro Gly Pro Pro Gly Glu Gly Arg 485 490 495 Ala Gly Glu Pro Gly Thr Ala Gly Pro Thr Gly Pro Pro Gly Val Pro 500 505 510 Gly Ser Pro Gly Ile Thr Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 515 520 525 Pro Pro Gly Ala Pro Gly Ala Phe Asp Glu Thr Gly Ile Ala Gly Leu 530 535 540 His Leu Pro Asn Gly Gly Val Glu Gly Ala Val Leu Gly Lys Gly Gly 545 550 555 560 Lys Pro Gln Phe Gly Leu Gly Glu Leu Ser Ala His Ala Thr Pro Ala 565 570 575 Phe Thr Ala Val Leu Thr Ser Pro Phe Pro Ala Ser Gly Met Pro Val 580 585 590 Lys Phe Asp Arg Thr Leu Tyr Asn Gly His Ser Gly Tyr Asn Pro Ala 595 600 605 Thr Gly Ile Phe Thr Cys Pro Val Gly Gly Val Tyr Tyr Phe Ala Tyr 610 615 620 His Val His Val Lys Gly Thr Asn Val Trp Val Ala Leu Tyr Lys Asn 625 630 635 640 Asn Val Pro Ala Thr Tyr Thr Tyr Asp Glu Tyr Lys Lys Gly Tyr Leu 645 650 655 Asp Gln Ala Ser Gly Gly Ala Val Leu Gln Leu Arg Pro Asn Asp Gln 660 665 670 Val Trp Val Gln Met Pro Ser Asp Gln Ala Asn Gly Leu Tyr Ser Thr 675 680 685 Glu Tyr Ile His Ser Ser Phe Ser Gly Phe Leu Leu Cys Pro Thr 690 695 700 <![CDATA[<210> 149]]> <![CDATA[<211> 323]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 149]]> Met Ala Ser Glu Phe Lys Lys Lys Leu Phe Trp Arg Ala Val Val Ala 1 5 10 15 Glu Phe Leu Ala Thr Thr Leu Phe Val Phe Ile Ser Ile Gly Ser Ala 20 25 30 Leu Gly Phe Lys Tyr Pro Val Gly Asn Asn Gln Thr Ala Val Gln Asp 35 40 45 Asn Val Lys Val Ser Leu Ala Phe Gly Leu Ser Ile Ala Thr Leu Ala 50 55 60 Gln Ser Val Gly His Ile Ser Gly Ala His Leu Asn Pro Ala Val Thr 65 70 75 80 Leu Gly Leu Leu Leu Ser Cys Gln Ile Ser Ile Phe Arg Ala Leu Met 85 90 95 Tyr Ile Ile Ala Gln Cys Val Gly Ala Ile Val Ala Thr Ala Ile Leu 100 105 110 Ser Gly Ile Thr Ser Ser Leu Thr Gly Asn Ser Leu Gly Arg Asn Asp 115 120 125 Leu Ala Asp Gly Val Asn Ser Gly Gln Gly Leu Gly Ile Glu Ile Ile 130 135 140 Gly Thr Leu Gln Leu Val Leu Cys Val Leu Ala Thr Thr Asp Arg Arg 145 150 155 160 Arg Arg Asp Leu Gly Gly Ser Ala Pro Leu Ala Ile Gly Leu Ser Val 165 170 175 Ala Leu Gly His Leu Leu Ala Ile Asp Tyr Thr Gly Cys Gly Ile Asn 180 185 190 Pro Ala Arg Ser Phe Gly Ser Ala Val Ile Thr His Asn Phe Ser Asn 195 200 205 His Trp Ile Phe Trp Val Gly Pro Phe Ile Gly Gly Ala Leu Ala Val 210 215 220 Leu Ile Tyr Asp Phe Ile Leu Ala Pro Arg Ser Ser Asp Leu Thr Asp 225 230 235 240 Arg Val Lys Val Trp Thr Ser Gly Gln Val Glu Glu Tyr Asp Leu Asp 245 250 255 Ala Asp Asp Ile Asn Ser Arg Ser Phe Leu Gly Thr Lys Ile Tyr Gln 260 265 270 Phe Thr His Ser Leu Glu Val Val Glu Glu Val Lys Glu Arg Asp Pro 275 280 285 Pro Ala Ser Arg Pro Ser Glu His Asp Gly Arg Cys Ala Arg Lys Ser 290 295 300 Pro Leu Ala Pro Lys Leu Leu Thr Asp Ser Pro Ala Gln Val Pro Gly 305 310 315 320 Ile Leu Pro <![CDATA[<210> 150]]> <![CDATA[<211> 269]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 150]]> Met Ala Ser Glu Phe Lys Lys Lys Leu Phe Trp Arg Ala Val Val Ala 1 5 10 15 Glu Phe Leu Ala Thr Thr Leu Phe Val Phe Ile Ser Ile Gly Ser Ala 20 25 30 Leu Gly Phe Lys Tyr Pro Val Gly Asn Asn Gln Thr Ala Val Gln Asp 35 40 45 Asn Val Lys Val Ser Leu Ala Phe Gly Leu Ser Ile Ala Thr Leu Ala 50 55 60 Gln Ser Val Gly His Ile Ser Gly Ala His Leu Asn Pro Ala Val Thr 65 70 75 80 Leu Gly Leu Leu Leu Ser Cys Gln Ile Ser Ile Phe Arg Ala Leu Met 85 90 95 Tyr Ile Ile Ala Gln Cys Val Gly Ala Ile Val Ala Thr Ala Ile Leu 100 105 110 Ser Gly Ile Thr Ser Ser Leu Thr Gly Asn Ser Leu Gly Arg Asn Asp 115 120 125 Leu Ala Asp Gly Val Asn Ser Gly Gln Gly Leu Gly Ile Glu Ile Ile 130 135 140 Gly Thr Leu Gln Leu Val Leu Cys Val Leu Ala Thr Thr Asp Arg Arg 145 150 155 160 Arg Arg Asp Leu Gly Gly Ser Ala Pro Leu Ala Ile Gly Leu Ser Val 165 170 175 Ala Leu Gly His Leu Leu Ala Ile Asp Tyr Thr Gly Cys Gly Ile Asn 180 185 190 Pro Ala Arg Ser Phe Gly Ser Ala Val Ile Thr His Asn Phe Ser Asn 195 200 205 His Trp Ile Phe Trp Val Gly Pro Phe Ile Gly Gly Ala Leu Ala Val 210 215 220 Leu Ile Tyr Asp Phe Ile Leu Ala Pro Arg Ser Ser Asp Leu Thr Asp 225 230 235 240 Arg Val Lys Val Trp Thr Ser Gly Gln Val Glu Glu Tyr Asp Leu Asp 245 250 255 Ala Asp Asp Ile Asn Ser Arg Val Glu Met Lys Pro Lys 260 265 <![CDATA[<210> 151]]> <![CDATA[<211> 1023]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 151]]> Met Gly Lys Gly Val Gly Arg Asp Lys Tyr Glu Pro Ala Ala Val Ser 1 5 10 15 Glu Gln Gly Asp Lys Lys Gly Lys Lys Gly Lys Lys Asp Arg Asp Met 20 25 30 Asp Glu Leu Lys Lys Glu Val Ser Met Asp Asp His Lys Leu Ser Leu 35 40 45 Asp Glu Leu His Arg Lys Tyr Gly Thr Asp Leu Ser Arg Gly Leu Thr 50 55 60 Ser Ala Arg Ala Ala Glu Ile Leu Ala Arg Asp Gly Pro Asn Ala Leu 65 70 75 80 Thr Pro Pro Pro Thr Thr Pro Glu Trp Ile Lys Phe Cys Arg Gln Leu 85 90 95 Phe Gly Gly Phe Ser Met Leu Leu Trp Ile Gly Ala Ile Leu Cys Phe 100 105 110 Leu Ala Tyr Ser Ile Gln Ala Ala Thr Glu Glu Glu Pro Gln Asn Asp 115 120 125 Asn Leu Tyr Leu Gly Val Val Leu Ser Ala Val Val Ile Ile Thr Gly 130 135 140 Cys Phe Ser Tyr Tyr Gln Glu Ala Lys Ser Ser Lys Ile Met Glu Ser 145 150 155 160 Phe Lys Asn Met Val Pro Gln Gln Ala Leu Val Ile Arg Asn Gly Glu 165 170 175 Lys Met Ser Ile Asn Ala Glu Glu Val Val Val Gly Asp Leu Val Glu 180 185 190 Val Lys Gly Gly Asp Arg Ile Pro Ala Asp Leu Arg Ile Ile Ser Ala 195 200 205 Asn Gly Cys Lys Val Asp Asn Ser Ser Leu Thr Gly Glu Ser Glu Pro 210 215 220 Gln Thr Arg Ser Pro Asp Phe Thr Asn Glu Asn Pro Leu Glu Thr Arg 225 230 235 240 Asn Ile Ala Phe Phe Ser Thr Asn Cys Val Glu Gly Thr Ala Arg Gly 245 250 255 Ile Val Val Tyr Thr Gly Asp Arg Thr Val Met Gly Arg Ile Ala Thr 260 265 270 Leu Ala Ser Gly Leu Glu Gly Gly Gln Thr Pro Ile Ala Ala Glu Ile 275 280 285 Glu His Phe Ile His Ile Ile Thr Gly Val Ala Val Phe Leu Gly Val 290 295 300 Ser Phe Phe Ile Leu Ser Leu Ile Leu Glu Tyr Thr Trp Leu Glu Ala 305 310 315 320 Val Ile Phe Leu Ile Gly Ile Ile Val Ala Asn Val Pro Glu Gly Leu 325 330 335 Leu Ala Thr Val Thr Val Cys Leu Thr Leu Thr Ala Lys Arg Met Ala 340 345 350 Arg Lys Asn Cys Leu Val Lys Asn Leu Glu Ala Val Glu Thr Leu Gly 355 360 365 Ser Thr Ser Thr Ile Cys Ser Asp Lys Thr Gly Thr Leu Thr Gln Asn 370 375 380 Arg Met Thr Val Ala His Met Trp Phe Asp Asn Gln Ile His Glu Ala 385 390 395 400 Asp Thr Thr Glu Asn Gln Ser Gly Val Ser Phe Asp Lys Thr Ser Ala 405 410 415 Thr Trp Leu Ala Leu Ser Arg Ile Ala Gly Leu Cys Asn Arg Ala Val 420 425 430 Phe Gln Ala Asn Gln Glu Asn Leu Pro Ile Leu Lys Arg Ala Val Ala 435 440 445 Gly Asp Ala Ser Glu Ser Ala Leu Leu Lys Cys Ile Glu Leu Cys Cys 450 455 460 Gly Ser Val Lys Glu Met Arg Glu Arg Tyr Ala Lys Ile Val Glu Ile 465 470 475 480 Pro Phe Asn Ser Thr Asn Lys Tyr Gln Leu Ser Ile His Lys Asn Pro 485 490 495 Asn Thr Ser Glu Pro Gln His Leu Leu Val Met Lys Gly Ala Pro Glu 500 505 510 Arg Ile Leu Asp Arg Cys Ser Ser Ile Leu Leu His Gly Lys Glu Gln 515 520 525 Pro Leu Asp Glu Glu Leu Lys Asp Ala Phe Gln Asn Ala Tyr Leu Glu 530 535 540 Leu Gly Gly Leu Gly Glu Arg Val Leu Gly Phe Cys His Leu Phe Leu 545 550 555 560 Pro Asp Glu Gln Phe Pro Glu Gly Phe Gln Phe Asp Thr Asp Asp Val 565 570 575 Asn Phe Pro Ile Asp Asn Leu Cys Phe Val Gly Leu Ile Ser Met Ile 580 585 590 Asp Pro Pro Arg Ala Ala Val Pro Asp Ala Val Gly Lys Cys Arg Ser 595 600 605 Ala Gly Ile Lys Val Ile Met Val Thr Gly Asp His Pro Ile Thr Ala 610 615 620 Lys Ala Ile Ala Lys Gly Val Gly Ile Ile Ser Glu Gly Asn Glu Thr 625 630 635 640 Val Glu Asp Ile Ala Ala Arg Leu Asn Ile Pro Val Ser Gln Val Asn 645 650 655 Pro Arg Asp Ala Lys Ala Cys Val Val His Gly Ser Asp Leu Lys Asp 660 665 670 Met Thr Ser Glu Gln Leu Asp Asp Ile Leu Lys Tyr His Thr Glu Ile 675 680 685 Val Phe Ala Arg Thr Ser Pro Gln Gln Lys Leu Ile Ile Val Glu Gly 690 695 700 Cys Gln Arg Gln Gly Ala Ile Val Ala Val Thr Gly Asp Gly Val Asn 705 710 715 720 Asp Ser Pro Ala Leu Lys Lys Ala Asp Ile Gly Val Ala Met Gly Ile 725 730 735 Ala Gly Ser Asp Val Ser Lys Gln Ala Ala Asp Met Ile Leu Leu Asp 740 745 750 Asp Asn Phe Ala Ser Ile Val Thr Gly Val Glu Glu Gly Arg Leu Ile 755 760 765 Phe Asp Asn Leu Lys Lys Ser Ile Ala Tyr Thr Leu Thr Ser Asn Ile 770 775 780 Pro Glu Ile Thr Pro Phe Leu Ile Phe Ile Ile Ala Asn Ile Pro Leu 785 790 795 800 Pro Leu Gly Thr Val Thr Ile Leu Cys Ile Asp Leu Gly Thr Asp Met 805 810 815 Val Pro Ala Ile Ser Leu Ala Tyr Glu Gln Ala Glu Ser Asp Ile Met 820 825 830 Lys Arg Gln Pro Arg Asn Pro Lys Thr Asp Lys Leu Val Asn Glu Arg 835 840 845 Leu Ile Ser Met Ala Tyr Gly Gln Ile Gly Met Ile Gln Ala Leu Gly 850 855 860 Gly Phe Phe Thr Tyr Phe Val Ile Leu Ala Glu Asn Gly Phe Leu Pro 865 870 875 880 Ile His Leu Leu Gly Leu Arg Val Asp Trp Asp Asp Arg Trp Ile Asn 885 890 895 Asp Val Glu Asp Ser Tyr Gly Gln Gln Trp Thr Tyr Glu Gln Arg Lys 900 905 910 Ile Val Glu Phe Thr Cys His Thr Ala Phe Phe Val Ser Ile Val Val 915 920 925 Val Gln Trp Ala Asp Leu Val Ile Cys Lys Thr Arg Arg Asn Ser Val 930 935 940 Phe Gln Gln Gly Met Lys Asn Lys Ile Leu Ile Phe Gly Leu Phe Glu 945 950 955 960 Glu Thr Ala Leu Ala Ala Phe Leu Ser Tyr Cys Pro Gly Met Gly Val 965 970 975 Ala Leu Arg Met Tyr Pro Leu Lys Pro Thr Trp Trp Phe Cys Ala Phe 980 985 990 Pro Tyr Ser Leu Leu Ile Phe Val Tyr Asp Glu Val Arg Lys Leu Ile 995 1000 1005 Ile Arg Arg Arg Pro Gly Gly Trp Val Glu Lys Glu Thr Tyr Tyr 1010 1015 1020 <![CDATA[<210> 152]]> <![CDATA[<211> 1023]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 152]]> Met Ala Phe Lys Val Gly Arg Asp Lys Tyr Glu Pro Ala Ala Val Ser 1 5 10 15 Glu Gln Gly Asp Lys Lys Gly Lys Lys Gly Lys Lys Asp Arg Asp Met 20 25 30 Asp Glu Leu Lys Lys Glu Val Ser Met Asp Asp His Lys Leu Ser Leu 35 40 45 Asp Glu Leu His Arg Lys Tyr Gly Thr Asp Leu Ser Arg Gly Leu Thr 50 55 60 Ser Ala Arg Ala Ala Glu Ile Leu Ala Arg Asp Gly Pro Asn Ala Leu 65 70 75 80 Thr Pro Pro Pro Thr Thr Pro Glu Trp Ile Lys Phe Cys Arg Gln Leu 85 90 95 Phe Gly Gly Phe Ser Met Leu Leu Trp Ile Gly Ala Ile Leu Cys Phe 100 105 110 Leu Ala Tyr Ser Ile Gln Ala Ala Thr Glu Glu Glu Pro Gln Asn Asp 115 120 125 Asn Leu Tyr Leu Gly Val Val Leu Ser Ala Val Val Ile Ile Thr Gly 130 135 140 Cys Phe Ser Tyr Tyr Gln Glu Ala Lys Ser Ser Lys Ile Met Glu Ser 145 150 155 160 Phe Lys Asn Met Val Pro Gln Gln Ala Leu Val Ile Arg Asn Gly Glu 165 170 175 Lys Met Ser Ile Asn Ala Glu Glu Val Val Val Gly Asp Leu Val Glu 180 185 190 Val Lys Gly Gly Asp Arg Ile Pro Ala Asp Leu Arg Ile Ile Ser Ala 195 200 205 Asn Gly Cys Lys Val Asp Asn Ser Ser Leu Thr Gly Glu Ser Glu Pro 210 215 220 Gln Thr Arg Ser Pro Asp Phe Thr Asn Glu Asn Pro Leu Glu Thr Arg 225 230 235 240 Asn Ile Ala Phe Phe Ser Thr Asn Cys Val Glu Gly Thr Ala Arg Gly 245 250 255 Ile Val Val Tyr Thr Gly Asp Arg Thr Val Met Gly Arg Ile Ala Thr 260 265 270 Leu Ala Ser Gly Leu Glu Gly Gly Gln Thr Pro Ile Ala Ala Glu Ile 275 280 285 Glu His Phe Ile His Ile Ile Thr Gly Val Ala Val Phe Leu Gly Val 290 295 300 Ser Phe Phe Ile Leu Ser Leu Ile Leu Glu Tyr Thr Trp Leu Glu Ala 305 310 315 320 Val Ile Phe Leu Ile Gly Ile Ile Val Ala Asn Val Pro Glu Gly Leu 325 330 335 Leu Ala Thr Val Thr Val Cys Leu Thr Leu Thr Ala Lys Arg Met Ala 340 345 350 Arg Lys Asn Cys Leu Val Lys Asn Leu Glu Ala Val Glu Thr Leu Gly 355 360 365 Ser Thr Ser Thr Ile Cys Ser Asp Lys Thr Gly Thr Leu Thr Gln Asn 370 375 380 Arg Met Thr Val Ala His Met Trp Phe Asp Asn Gln Ile His Glu Ala 385 390 395 400 Asp Thr Thr Glu Asn Gln Ser Gly Val Ser Phe Asp Lys Thr Ser Ala 405 410 415 Thr Trp Leu Ala Leu Ser Arg Ile Ala Gly Leu Cys Asn Arg Ala Val 420 425 430 Phe Gln Ala Asn Gln Glu Asn Leu Pro Ile Leu Lys Arg Ala Val Ala 435 440 445 Gly Asp Ala Ser Glu Ser Ala Leu Leu Lys Cys Ile Glu Leu Cys Cys 450 455 460 Gly Ser Val Lys Glu Met Arg Glu Arg Tyr Ala Lys Ile Val Glu Ile 465 470 475 480 Pro Phe Asn Ser Thr Asn Lys Tyr Gln Leu Ser Ile His Lys Asn Pro 485 490 495 Asn Thr Ser Glu Pro Gln His Leu Leu Val Met Lys Gly Ala Pro Glu 500 505 510 Arg Ile Leu Asp Arg Cys Ser Ser Ile Leu Leu His Gly Lys Glu Gln 515 520 525 Pro Leu Asp Glu Glu Leu Lys Asp Ala Phe Gln Asn Ala Tyr Leu Glu 530 535 540 Leu Gly Gly Leu Gly Glu Arg Val Leu Gly Phe Cys His Leu Phe Leu 545 550 555 560 Pro Asp Glu Gln Phe Pro Glu Gly Phe Gln Phe Asp Thr Asp Asp Val 565 570 575 Asn Phe Pro Ile Asp Asn Leu Cys Phe Val Gly Leu Ile Ser Met Ile 580 585 590 Asp Pro Pro Arg Ala Ala Val Pro Asp Ala Val Gly Lys Cys Arg Ser 595 600 605 Ala Gly Ile Lys Val Ile Met Val Thr Gly Asp His Pro Ile Thr Ala 610 615 620 Lys Ala Ile Ala Lys Gly Val Gly Ile Ile Ser Glu Gly Asn Glu Thr 625 630 635 640 Val Glu Asp Ile Ala Ala Arg Leu Asn Ile Pro Val Ser Gln Val Asn 645 650 655 Pro Arg Asp Ala Lys Ala Cys Val Val His Gly Ser Asp Leu Lys Asp 660 665 670 Met Thr Ser Glu Gln Leu Asp Asp Ile Leu Lys Tyr His Thr Glu Ile 675 680 685 Val Phe Ala Arg Thr Ser Pro Gln Gln Lys Leu Ile Ile Val Glu Gly 690 695 700 Cys Gln Arg Gln Gly Ala Ile Val Ala Val Thr Gly Asp Gly Val Asn 705 710 715 720 Asp Ser Pro Ala Leu Lys Lys Ala Asp Ile Gly Val Ala Met Gly Ile 725 730 735 Ala Gly Ser Asp Val Ser Lys Gln Ala Ala Asp Met Ile Leu Leu Asp 740 745 750 Asp Asn Phe Ala Ser Ile Val Thr Gly Val Glu Glu Gly Arg Leu Ile 755 760 765 Phe Asp Asn Leu Lys Lys Ser Ile Ala Tyr Thr Leu Thr Ser Asn Ile 770 775 780 Pro Glu Ile Thr Pro Phe Leu Ile Phe Ile Ile Ala Asn Ile Pro Leu 785 790 795 800 Pro Leu Gly Thr Val Thr Ile Leu Cys Ile Asp Leu Gly Thr Asp Met 805 810 815 Val Pro Ala Ile Ser Leu Ala Tyr Glu Gln Ala Glu Ser Asp Ile Met 820 825 830 Lys Arg Gln Pro Arg Asn Pro Lys Thr Asp Lys Leu Val Asn Glu Arg 835 840 845 Leu Ile Ser Met Ala Tyr Gly Gln Ile Gly Met Ile Gln Ala Leu Gly 850 855 860 Gly Phe Phe Thr Tyr Phe Val Ile Leu Ala Glu Asn Gly Phe Leu Pro 865 870 875 880 Ile His Leu Leu Gly Leu Arg Val Asp Trp Asp Asp Arg Trp Ile Asn 885 890 895 Asp Val Glu Asp Ser Tyr Gly Gln Gln Trp Thr Tyr Glu Gln Arg Lys 900 905 910 Ile Val Glu Phe Thr Cys His Thr Ala Phe Phe Val Ser Ile Val Val 915 920 925 Val Gln Trp Ala Asp Leu Val Ile Cys Lys Thr Arg Arg Asn Ser Val 930 935 940 Phe Gln Gln Gly Met Lys Asn Lys Ile Leu Ile Phe Gly Leu Phe Glu 945 950 955 960 Glu Thr Ala Leu Ala Ala Phe Leu Ser Tyr Cys Pro Gly Met Gly Val 965 970 975 Ala Leu Arg Met Tyr Pro Leu Lys Pro Thr Trp Trp Phe Cys Ala Phe 980 985 990 Pro Tyr Ser Leu Leu Ile Phe Val Tyr Asp Glu Val Arg Lys Leu Ile 995 1000 1005 Ile Arg Arg Arg Pro Gly Gly Trp Val Glu Lys Glu Thr Tyr Tyr 1010 1015 1020 <![CDATA[<210> 153]]> <![CDATA[<211> 992]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 153]]> Met Asp Glu Leu Lys Lys Glu Val Ser Met Asp Asp His Lys Leu Ser 1 5 10 15 Leu Asp Glu Leu His Arg Lys Tyr Gly Thr Asp Leu Ser Arg Gly Leu 20 25 30 Thr Ser Ala Arg Ala Ala Glu Ile Leu Ala Arg Asp Gly Pro Asn Ala 35 40 45 Leu Thr Pro Pro Pro Thr Thr Pro Glu Trp Ile Lys Phe Cys Arg Gln 50 55 60 Leu Phe Gly Gly Phe Ser Met Leu Leu Trp Ile Gly Ala Ile Leu Cys 65 70 75 80 Phe Leu Ala Tyr Ser Ile Gln Ala Ala Thr Glu Glu Glu Pro Gln Asn 85 90 95 Asp Asn Leu Tyr Leu Gly Val Val Leu Ser Ala Val Val Ile Ile Thr 100 105 110 Gly Cys Phe Ser Tyr Tyr Gln Glu Ala Lys Ser Ser Lys Ile Met Glu 115 120 125 Ser Phe Lys Asn Met Val Pro Gln Gln Ala Leu Val Ile Arg Asn Gly 130 135 140 Glu Lys Met Ser Ile Asn Ala Glu Glu Val Val Val Gly Asp Leu Val 145 150 155 160 Glu Val Lys Gly Gly Asp Arg Ile Pro Ala Asp Leu Arg Ile Ile Ser 165 170 175 Ala Asn Gly Cys Lys Val Asp Asn Ser Ser Leu Thr Gly Glu Ser Glu 180 185 190 Pro Gln Thr Arg Ser Pro Asp Phe Thr Asn Glu Asn Pro Leu Glu Thr 195 200 205 Arg Asn Ile Ala Phe Phe Ser Thr Asn Cys Val Glu Gly Thr Ala Arg 210 215 220 Gly Ile Val Val Tyr Thr Gly Asp Arg Thr Val Met Gly Arg Ile Ala 225 230 235 240 Thr Leu Ala Ser Gly Leu Glu Gly Gly Gln Thr Pro Ile Ala Ala Glu 245 250 255 Ile Glu His Phe Ile His Ile Ile Thr Gly Val Ala Val Phe Leu Gly 260 265 270 Val Ser Phe Phe Ile Leu Ser Leu Ile Leu Glu Tyr Thr Trp Leu Glu 275 280 285 Ala Val Ile Phe Leu Ile Gly Ile Ile Val Ala Asn Val Pro Glu Gly 290 295 300 Leu Leu Ala Thr Val Thr Val Cys Leu Thr Leu Thr Ala Lys Arg Met 305 310 315 320 Ala Arg Lys Asn Cys Leu Val Lys Asn Leu Glu Ala Val Glu Thr Leu 325 330 335 Gly Ser Thr Ser Thr Ile Cys Ser Asp Lys Thr Gly Thr Leu Thr Gln 340 345 350 Asn Arg Met Thr Val Ala His Met Trp Phe Asp Asn Gln Ile His Glu 355 360 365 Ala Asp Thr Thr Glu Asn Gln Ser Gly Val Ser Phe Asp Lys Thr Ser 370 375 380 Ala Thr Trp Leu Ala Leu Ser Arg Ile Ala Gly Leu Cys Asn Arg Ala 385 390 395 400 Val Phe Gln Ala Asn Gln Glu Asn Leu Pro Ile Leu Lys Arg Ala Val 405 410 415 Ala Gly Asp Ala Ser Glu Ser Ala Leu Leu Lys Cys Ile Glu Leu Cys 420 425 430 Cys Gly Ser Val Lys Glu Met Arg Glu Arg Tyr Ala Lys Ile Val Glu 435 440 445 Ile Pro Phe Asn Ser Thr Asn Lys Tyr Gln Leu Ser Ile His Lys Asn 450 455 460 Pro Asn Thr Ser Glu Pro Gln His Leu Leu Val Met Lys Gly Ala Pro 465 470 475 480 Glu Arg Ile Leu Asp Arg Cys Ser Ser Ile Leu Leu His Gly Lys Glu 485 490 495 Gln Pro Leu Asp Glu Glu Leu Lys Asp Ala Phe Gln Asn Ala Tyr Leu 500 505 510 Glu Leu Gly Gly Leu Gly Glu Arg Val Leu Gly Phe Cys His Leu Phe 515 520 525 Leu Pro Asp Glu Gln Phe Pro Glu Gly Phe Gln Phe Asp Thr Asp Asp 530 535 540 Val Asn Phe Pro Ile Asp Asn Leu Cys Phe Val Gly Leu Ile Ser Met 545 550 555 560 Ile Asp Pro Pro Arg Ala Ala Val Pro Asp Ala Val Gly Lys Cys Arg 565 570 575 Ser Ala Gly Ile Lys Val Ile Met Val Thr Gly Asp His Pro Ile Thr 580 585 590 Ala Lys Ala Ile Ala Lys Gly Val Gly Ile Ile Ser Glu Gly Asn Glu 595 600 605 Thr Val Glu Asp Ile Ala Ala Arg Leu Asn Ile Pro Val Ser Gln Val 610 615 620 Asn Pro Arg Asp Ala Lys Ala Cys Val Val His Gly Ser Asp Leu Lys 625 630 635 640 Asp Met Thr Ser Glu Gln Leu Asp Asp Ile Leu Lys Tyr His Thr Glu 645 650 655 Ile Val Phe Ala Arg Thr Ser Pro Gln Gln Lys Leu Ile Ile Val Glu 660 665 670 Gly Cys Gln Arg Gln Gly Ala Ile Val Ala Val Thr Gly Asp Gly Val 675 680 685 Asn Asp Ser Pro Ala Leu Lys Lys Ala Asp Ile Gly Val Ala Met Gly 690 695 700 Ile Ala Gly Ser Asp Val Ser Lys Gln Ala Ala Asp Met Ile Leu Leu 705 710 715 720 Asp Asp Asn Phe Ala Ser Ile Val Thr Gly Val Glu Glu Gly Arg Leu 725 730 735 Ile Phe Asp Asn Leu Lys Lys Ser Ile Ala Tyr Thr Leu Thr Ser Asn 740 745 750 Ile Pro Glu Ile Thr Pro Phe Leu Ile Phe Ile Ile Ala Asn Ile Pro 755 760 765 Leu Pro Leu Gly Thr Val Thr Ile Leu Cys Ile Asp Leu Gly Thr Asp 770 775 780 Met Val Pro Ala Ile Ser Leu Ala Tyr Glu Gln Ala Glu Ser Asp Ile 785 790 795 800 Met Lys Arg Gln Pro Arg Asn Pro Lys Thr Asp Lys Leu Val Asn Glu 805 810 815 Arg Leu Ile Ser Met Ala Tyr Gly Gln Ile Gly Met Ile Gln Ala Leu 820 825 830 Gly Gly Phe Phe Thr Tyr Phe Val Ile Leu Ala Glu Asn Gly Phe Leu 835 840 845 Pro Ile His Leu Leu Gly Leu Arg Val Asp Trp Asp Asp Arg Trp Ile 850 855 860 Asn Asp Val Glu Asp Ser Tyr Gly Gln Gln Trp Thr Tyr Glu Gln Arg 865 870 875 880 Lys Ile Val Glu Phe Thr Cys His Thr Ala Phe Phe Val Ser Ile Val 885 890 895 Val Val Gln Trp Ala Asp Leu Val Ile Cys Lys Thr Arg Arg Asn Ser 900 905 910 Val Phe Gln Gln Gly Met Lys Asn Lys Ile Leu Ile Phe Gly Leu Phe 915 920 925 Glu Glu Thr Ala Leu Ala Ala Phe Leu Ser Tyr Cys Pro Gly Met Gly 930 935 940 Val Ala Leu Arg Met Tyr Pro Leu Lys Pro Thr Trp Trp Phe Cys Ala 945 950 955 960 Phe Pro Tyr Ser Leu Leu Ile Phe Val Tyr Asp Glu Val Arg Lys Leu 965 970 975 Ile Ile Arg Arg Arg Pro Gly Gly Trp Val Glu Lys Glu Thr Tyr Tyr 980 985 990 <![CDATA[<210> 154]]> <![CDATA[<211> 1861]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 154]]> Met Arg Arg Leu Glu Gly Leu Cys Leu Arg Arg Arg Arg Arg Arg Arg 1 5 10 15 Gly Pro Ala Arg Glu Arg Ser Gly Asp Lys Met Lys Tyr Gln Lys Tyr 20 25 30 Leu Thr Val Leu Gln Met Ala Ile Gly Val Thr Pro Ser Asn Arg Gly 35 40 45 Ser Leu Leu Pro Leu Lys Arg Lys Leu Trp Val Thr Pro Ser Ser Glu 50 55 60 Asn Pro Asn Gly Ala Thr Ser Ser Val Ser Gln Gly Lys Pro Ser Leu 65 70 75 80 Arg Arg Ile Lys Gly Arg Leu His Arg Ser Lys Ser Leu Asp Ser Met 85 90 95 Asp Phe Cys Glu Leu Thr Ser Thr Ala Met Glu Glu Thr Ala Ile Trp 100 105 110 Glu Gln His Thr Val Thr Leu His Arg Ala Pro Gly Phe Gly Phe Gly 115 120 125 Ile Ala Ile Ser Gly Gly Arg Asp Asn Pro His Phe Gln Ser Gly Glu 130 135 140 Thr Ser Ile Val Ile Ser Asp Val Leu Lys Gly Gly Pro Ala Glu Gly 145 150 155 160 Gln Leu Gln Glu Asn Asp Arg Val Ala Met Val Asn Gly Val Ser Met 165 170 175 Asp Asn Val Glu His Ala Phe Ala Val Gln Gln Leu Arg Lys Ser Gly 180 185 190 Lys Asn Ala Lys Ile Thr Ile Arg Arg Lys Lys Lys Val Gln Ile Pro 195 200 205 Val Ser Arg Pro Asp Pro Glu Pro Val Ser Asp Asn Glu Glu Asp Ser 210 215 220 Tyr Asp Glu Glu Ile His Asp Pro Arg Ser Gly Arg Ser Gly Val Val 225 230 235 240 Asn Arg Arg Ser Glu Lys Ile Trp Pro Arg Asp Arg Ser Ala Ser Arg 245 250 255 Glu Arg Ser Leu Ser Pro Arg Ser Asp Arg Arg Ser Val Ala Ser Ser 260 265 270 Gln Pro Ala Lys Pro Thr Lys Val Thr Leu Val Lys Ser Arg Lys Asn 275 280 285 Glu Glu Tyr Gly Leu Arg Leu Ala Ser His Ile Phe Val Lys Glu Ile 290 295 300 Ser Gln Asp Ser Leu Ala Ala Arg Asp Gly Asn Ile Gln Glu Gly Asp 305 310 315 320 Val Val Leu Lys Ile Asn Gly Thr Val Thr Glu Asn Met Ser Leu Thr 325 330 335 Asp Ala Lys Thr Leu Ile Glu Arg Ser Lys Gly Lys Leu Lys Met Val 340 345 350 Val Gln Arg Asp Glu Arg Ala Thr Leu Leu Asn Val Pro Asp Leu Ser 355 360 365 Asp Ser Ile His Ser Ala Asn Ala Ser Glu Arg Asp Asp Ile Ser Glu 370 375 380 Ile Gln Ser Leu Ala Ser Asp His Ser Gly Arg Ser His Asp Arg Pro 385 390 395 400 Pro Arg Arg Ser Arg Ser Arg Ser Pro Asp Gln Arg Ser Glu Pro Ser 405 410 415 Asp His Ser Arg His Ser Pro Gln Gln Pro Ser Asn Gly Ser Leu Arg 420 425 430 Ser Arg Asp Glu Glu Arg Ile Ser Lys Pro Gly Ala Val Ser Thr Pro 435 440 445 Val Lys His Ala Asp Asp His Thr Pro Lys Thr Val Glu Glu Val Thr 450 455 460 Val Glu Arg Asn Glu Lys Gln Thr Pro Ser Leu Pro Glu Pro Lys Pro 465 470 475 480 Val Tyr Ala Gln Val Gly Gln Pro Asp Val Asp Leu Pro Val Ser Pro 485 490 495 Ser Asp Gly Val Leu Pro Asn Ser Thr His Glu Asp Gly Ile Leu Arg 500 505 510 Pro Ser Met Lys Leu Val Lys Phe Arg Lys Gly Asp Ser Val Gly Leu 515 520 525 Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val Ala Gly Val Leu 530 535 540 Glu Asp Ser Pro Ala Ala Lys Glu Gly Leu Glu Glu Gly Asp Gln Ile 545 550 555 560 Leu Arg Val Asn Asn Val Asp Phe Thr Asn Ile Ile Arg Glu Glu Ala 565 570 575 Val Leu Phe Leu Leu Asp Leu Pro Lys Gly Glu Glu Val Thr Ile Leu 580 585 590 Ala Gln Lys Lys Lys Asp Val Tyr Arg Arg Ile Val Glu Ser Asp Val 595 600 605 Gly Asp Ser Phe Tyr Ile Arg Thr His Phe Glu Tyr Glu Lys Glu Ser 610 615 620 Pro Tyr Gly Leu Ser Phe Asn Lys Gly Glu Val Phe Arg Val Val Asp 625 630 635 640 Thr Leu Tyr Asn Gly Lys Leu Gly Ser Trp Leu Ala Ile Arg Ile Gly 645 650 655 Lys Asn His Lys Glu Val Glu Arg Gly Ile Ile Pro Asn Lys Asn Arg 660 665 670 Ala Glu Gln Leu Ala Ser Val Gln Tyr Thr Leu Pro Lys Thr Ala Gly 675 680 685 Gly Asp Arg Ala Asp Phe Trp Arg Phe Arg Gly Leu Arg Ser Ser Lys 690 695 700 Arg Asn Leu Arg Lys Ser Arg Glu Asp Leu Ser Ala Gln Pro Val Gln 705 710 715 720 Thr Lys Phe Pro Ala Tyr Glu Arg Val Val Leu Arg Glu Ala Gly Phe 725 730 735 Leu Arg Pro Val Thr Ile Phe Gly Pro Ile Ala Asp Val Ala Arg Glu 740 745 750 Lys Leu Ala Arg Glu Glu Pro Asp Ile Tyr Gln Ile Ala Lys Ser Glu 755 760 765 Pro Arg Asp Ala Gly Thr Asp Gln Arg Ser Ser Gly Ile Ile Arg Leu 770 775 780 His Thr Ile Lys Gln Ile Ile Asp Gln Asp Lys His Ala Leu Leu Asp 785 790 795 800 Val Thr Pro Asn Ala Val Asp Arg Leu Asn Tyr Ala Gln Trp Tyr Pro 805 810 815 Ile Val Val Phe Leu Asn Pro Asp Ser Lys Gln Gly Val Lys Thr Met 820 825 830 Arg Met Arg Leu Cys Pro Glu Ser Arg Lys Ser Ala Arg Lys Leu Tyr 835 840 845 Glu Arg Ser His Lys Leu Arg Lys Asn Asn His His Leu Phe Thr Thr 850 855 860 Thr Ile Asn Leu Asn Ser Met Asn Asp Gly Trp Tyr Gly Ala Leu Lys 865 870 875 880 Glu Ala Ile Gln Gln Gln Gln Asn Gln Leu Val Trp Val Ser Glu Gly 885 890 895 Lys Ala Asp Gly Ala Thr Ser Asp Asp Leu Asp Leu His Asp Asp Arg 900 905 910 Leu Ser Tyr Leu Ser Ala Pro Gly Ser Glu Tyr Ser Met Tyr Ser Thr 915 920 925 Asp Ser Arg His Thr Ser Asp Tyr Glu Asp Thr Asp Thr Glu Gly Gly 930 935 940 Ala Tyr Thr Asp Gln Glu Leu Asp Glu Thr Leu Asn Asp Glu Val Gly 945 950 955 960 Thr Pro Pro Glu Ser Ala Ile Thr Arg Ser Ser Glu Pro Val Arg Glu 965 970 975 Asp Ser Ser Gly Met His His Glu Asn Gln Thr Tyr Pro Pro Tyr Ser 980 985 990 Pro Gln Ala Gln Pro Gln Pro Ile His Arg Ile Asp Ser Pro Gly Phe 995 1000 1005 Lys Pro Ala Ser Gln Gln Lys Ala Glu Ala Ser Ser Pro Val Pro 1010 1015 1020 Tyr Leu Ser Pro Glu Thr Asn Pro Ala Ser Ser Thr Ser Ala Val 1025 1030 1035 Asn His Asn Val Asn Leu Thr Asn Val Arg Leu Glu Glu Pro Thr 1040 1045 1050 Pro Ala Pro Ser Thr Ser Tyr Ser Pro Gln Ala Asp Ser Leu Arg 1055 1060 1065 Thr Pro Ser Thr Glu Ala Ala His Ile Met Leu Arg Asp Gln Glu 1070 1075 1080 Pro Ser Leu Ser Ser His Val Asp Pro Thr Lys Val Tyr Arg Lys 1085 1090 1095 Asp Pro Tyr Pro Glu Glu Met Met Arg Gln Asn His Val Leu Lys 1100 1105 1110 Gln Pro Ala Val Ser His Pro Gly His Arg Pro Asp Lys Glu Pro 1115 1120 1125 Asn Leu Thr Tyr Glu Pro Gln Leu Pro Tyr Val Glu Lys Gln Ala 1130 1135 1140 Ser Arg Asp Leu Glu Gln Pro Thr Tyr Arg Tyr Glu Ser Ser Ser 1145 1150 1155 Tyr Thr Asp Gln Phe Ser Arg Asn Tyr Glu His Arg Leu Arg Tyr 1160 1165 1170 Glu Asp Arg Val Pro Met Tyr Glu Glu Gln Trp Ser Tyr Tyr Asp 1175 1180 1185 Asp Lys Gln Pro Tyr Pro Ser Arg Pro Pro Phe Asp Asn Gln His 1190 1195 1200 Ser Gln Asp Leu Asp Ser Arg Gln His Pro Glu Glu Ser Ser Glu 1205 1210 1215 Arg Gly Tyr Phe Pro Arg Phe Glu Glu Pro Ala Pro Leu Ser Tyr 1220 1225 1230 Asp Ser Arg Pro Arg Tyr Glu Gln Ala Pro Arg Ala Ser Ala Leu 1235 1240 1245 Arg His Glu Glu Gln Pro Ala Pro Gly Tyr Asp Thr His Gly Arg 1250 1255 1260 Leu Arg Pro Glu Ala Gln Pro His Pro Ser Ala Gly Pro Lys Pro 1265 1270 1275 Ala Glu Ser Lys Gln Tyr Phe Glu Gln Tyr Ser Arg Ser Tyr Glu 1280 1285 1290 Gln Val Pro Pro Gln Gly Phe Thr Ser Arg Ala Gly His Phe Glu 1295 1300 1305 Pro Leu His Gly Ala Ala Ala Val Pro Pro Leu Ile Pro Ser Ser 1310 1315 1320 Gln His Lys Pro Glu Ala Leu Pro Ser Asn Thr Lys Pro Leu Pro 1325 1330 1335 Pro Pro Pro Thr Gln Thr Glu Glu Glu Glu Asp Pro Ala Met Lys 1340 1345 1350 Pro Gln Ser Val Leu Thr Arg Val Lys Met Phe Glu Asn Lys Arg 1355 1360 1365 Ser Ala Ser Leu Glu Thr Lys Lys Asp Val Asn Asp Thr Gly Ser 1370 1375 1380 Phe Lys Pro Pro Glu Val Ala Ser Lys Pro Ser Gly Ala Pro Ile 1385 1390 1395 Ile Gly Pro Lys Pro Thr Ser Gln Asn Gln Phe Ser Glu His Asp 1400 1405 1410 Lys Thr Leu Tyr Arg Ile Pro Glu Pro Gln Lys Pro Gln Leu Lys 1415 1420 1425 Pro Pro Glu Asp Ile Val Arg Ser Asn His Tyr Asp Pro Glu Glu 1430 1435 1440 Asp Glu Glu Tyr Tyr Arg Lys Gln Leu Ser Tyr Phe Asp Arg Arg 1445 1450 1455 Ser Phe Glu Asn Lys Pro Pro Ala His Ile Ala Ala Ser His Leu 1460 1465 1470 Ser Glu Pro Ala Lys Pro Ala His Ser Gln Asn Gln Ser Asn Phe 1475 1480 1485 Ser Ser Tyr Ser Ser Lys Gly Lys Pro Pro Glu Ala Asp Gly Val 1490 1495 1500 Asp Arg Ser Phe Gly Glu Lys Arg Tyr Glu Pro Ile Gln Ala Thr 1505 1510 1515 Pro Pro Pro Pro Pro Leu Pro Ser Gln Tyr Ala Gln Pro Ser Gln 1520 1525 1530 Pro Val Thr Ser Ala Ser Leu His Ile His Ser Lys Gly Ala His 1535 1540 1545 Gly Glu Gly Asn Ser Val Ser Leu Asp Phe Gln Asn Ser Leu Val 1550 1555 1560 Ser Lys Pro Asp Pro Pro Pro Ser Gln Asn Lys Pro Ala Thr Phe 1565 1570 1575 Arg Pro Pro Asn Arg Glu Asp Thr Ala Gln Ala Ala Phe Tyr Pro 1580 1585 1590 Gln Lys Ser Phe Pro Asp Lys Ala Pro Val Asn Gly Thr Glu Gln 1595 1600 1605 Thr Gln Lys Thr Val Thr Pro Ala Tyr Asn Arg Phe Thr Pro Lys 1610 1615 1620 Pro Tyr Thr Ser Ser Ala Arg Pro Phe Glu Arg Lys Phe Glu Ser 1625 1630 1635 Pro Lys Phe Asn His Asn Leu Leu Pro Ser Glu Thr Ala His Lys 1640 1645 1650 Pro Asp Leu Ser Ser Lys Thr Pro Thr Ser Pro Lys Thr Leu Val 1655 1660 1665 Lys Ser His Ser Leu Ala Gln Pro Pro Glu Phe Asp Ser Gly Val 1670 1675 1680 Glu Thr Phe Ser Ile His Ala Glu Lys Pro Lys Tyr Gln Ile Asn 1685 1690 1695 Asn Ile Ser Thr Val Pro Lys Ala Ile Pro Val Ser Pro Ser Ala 1700 1705 1710 Val Glu Glu Asp Glu Asp Glu Asp Gly His Thr Val Val Ala Thr 1715 1720 1725 Ala Arg Gly Ile Phe Asn Ser Asn Gly Gly Val Leu Ser Ser Ile 1730 1735 1740 Glu Thr Gly Val Ser Ile Ile Ile Pro Gln Gly Ala Ile Pro Glu 1745 1750 1755 Gly Val Glu Gln Glu Ile Tyr Phe Lys Val Cys Arg Asp Asn Ser 1760 1765 1770 Ile Leu Pro Pro Leu Asp Lys Glu Lys Gly Glu Thr Leu Leu Ser 1775 1780 1785 Pro Leu Val Met Cys Gly Pro His Gly Leu Lys Phe Leu Lys Pro 1790 1795 1800 Val Glu Leu Arg Leu Pro His Cys Ala Ser Met Thr Pro Asp Gly 1805 1810 1815 Trp Ser Phe Ala Leu Lys Ser Ser Asp Ser Ser Ser Gly Asp Pro 1820 1825 1830 Lys Thr Trp Gln Asn Lys Cys Leu Pro Gly Asp Pro Asn Tyr Leu 1835 1840 1845 Val Gly Ala Asn Cys Val Ser Val Leu Ile Asp His Phe 1850 1855 1860 <![CDATA[<210> 155]]> <![CDATA[<211> 1692]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 155]]> Met Glu Arg Asn Thr Phe Ser Met Asp Cys His Ser Lys Ser Thr Ala 1 5 10 15 Met Glu Glu Thr Ala Ile Trp Glu Gln His Thr Val Thr Leu His Arg 20 25 30 Ala Pro Gly Phe Gly Phe Gly Ile Ala Ile Ser Gly Gly Arg Asp Asn 35 40 45 Pro His Phe Gln Ser Gly Glu Thr Ser Ile Val Ile Ser Asp Val Leu 50 55 60 Lys Gly Gly Pro Ala Glu Gly Gln Leu Gln Glu Asn Asp Arg Val Ala 65 70 75 80 Met Val Asn Gly Val Ser Met Asp Asn Val Glu His Ala Phe Ala Val 85 90 95 Gln Gln Leu Arg Lys Ser Gly Lys Asn Ala Lys Ile Thr Ile Arg Arg 100 105 110 Lys Lys Lys Val Gln Ile Pro Val Ser Arg Pro Asp Pro Glu Pro Val 115 120 125 Ser Asp Asn Glu Glu Asp Ser Tyr Asp Glu Glu Ile His Asp Pro Arg 130 135 140 Ser Gly Arg Ser Gly Val Val Asn Arg Arg Ser Glu Lys Ile Trp Pro 145 150 155 160 Arg Asp Arg Ser Ala Ser Arg Glu Arg Ser Leu Ser Pro Arg Ser Asp 165 170 175 Arg Arg Ser Val Ala Ser Ser Gln Pro Ala Lys Pro Thr Lys Val Thr 180 185 190 Leu Val Lys Ser Arg Lys Asn Glu Glu Tyr Gly Leu Arg Leu Ala Ser 195 200 205 His Ile Phe Val Lys Glu Ile Ser Gln Asp Ser Leu Ala Ala Arg Asp 210 215 220 Gly Asn Ile Gln Glu Gly Asp Val Val Leu Lys Ile Asn Gly Thr Val 225 230 235 240 Thr Glu Asn Met Ser Leu Thr Asp Ala Lys Thr Leu Ile Glu Arg Ser 245 250 255 Lys Gly Lys Leu Lys Met Val Val Gln Arg Asp Glu Arg Ala Thr Leu 260 265 270 Leu Asn Val Pro Asp Leu Ser Asp Ser Ile His Ser Ala Asn Ala Ser 275 280 285 Glu Arg Asp Asp Ile Ser Glu Ile Gln Ser Leu Ala Ser Asp His Ser 290 295 300 Gly Arg Ser His Asp Arg Pro Pro Arg Arg Ser Arg Ser Arg Ser Pro 305 310 315 320 Asp Gln Arg Ser Glu Pro Ser Asp His Ser Arg His Ser Pro Gln Gln 325 330 335 Pro Ser Asn Gly Ser Leu Arg Ser Arg Asp Glu Glu Arg Ile Ser Lys 340 345 350 Pro Gly Ala Val Ser Thr Pro Val Lys His Ala Asp Asp His Thr Pro 355 360 365 Lys Thr Val Glu Glu Val Thr Val Glu Arg Asn Glu Lys Gln Thr Pro 370 375 380 Ser Leu Pro Glu Pro Lys Pro Val Tyr Ala Gln Val Gly Gln Pro Asp 385 390 395 400 Val Asp Leu Pro Val Ser Pro Ser Asp Gly Val Leu Pro Asn Ser Thr 405 410 415 His Glu Asp Gly Ile Leu Arg Pro Ser Met Lys Leu Val Lys Phe Arg 420 425 430 Lys Gly Asp Ser Val Gly Leu Arg Leu Ala Gly Gly Asn Asp Val Gly 435 440 445 Ile Phe Val Ala Gly Val Leu Glu Asp Ser Pro Ala Ala Lys Glu Gly 450 455 460 Leu Glu Glu Gly Asp Gln Ile Leu Arg Val Asn Asn Val Asp Phe Thr 465 470 475 480 Asn Ile Ile Arg Glu Glu Ala Val Leu Phe Leu Leu Asp Leu Pro Lys 485 490 495 Gly Glu Glu Val Thr Ile Leu Ala Gln Lys Lys Lys Asp Val Tyr Arg 500 505 510 Arg Ile Val Glu Ser Asp Val Gly Asp Ser Phe Tyr Ile Arg Thr His 515 520 525 Phe Glu Tyr Glu Lys Glu Ser Pro Tyr Gly Leu Ser Phe Asn Lys Gly 530 535 540 Glu Val Phe Arg Val Val Asp Thr Leu Tyr Asn Gly Lys Leu Gly Ser 545 550 555 560 Trp Leu Ala Ile Arg Ile Gly Lys Asn His Lys Glu Val Glu Arg Gly 565 570 575 Ile Ile Pro Asn Lys Asn Arg Ala Glu Gln Leu Ala Ser Val Gln Tyr 580 585 590 Thr Leu Pro Lys Thr Ala Gly Gly Asp Arg Ala Asp Phe Trp Arg Phe 595 600 605 Arg Gly Leu Arg Ser Ser Lys Arg Asn Leu Arg Lys Ser Arg Glu Asp 610 615 620 Leu Ser Ala Gln Pro Val Gln Thr Lys Phe Pro Ala Tyr Glu Arg Val 625 630 635 640 Val Leu Arg Glu Ala Gly Phe Leu Arg Pro Val Thr Ile Phe Gly Pro 645 650 655 Ile Ala Asp Val Ala Arg Glu Lys Leu Ala Arg Glu Glu Pro Asp Ile 660 665 670 Tyr Gln Ile Ala Lys Ser Glu Pro Arg Asp Ala Gly Thr Asp Gln Arg 675 680 685 Ser Ser Gly Ile Ile Arg Leu His Thr Ile Lys Gln Ile Ile Asp Gln 690 695 700 Asp Lys His Ala Leu Leu Asp Val Thr Pro Asn Ala Val Asp Arg Leu 705 710 715 720 Asn Tyr Ala Gln Trp Tyr Pro Ile Val Val Phe Leu Asn Pro Asp Ser 725 730 735 Lys Gln Gly Val Lys Thr Met Arg Met Arg Leu Cys Pro Glu Ser Arg 740 745 750 Lys Ser Ala Arg Lys Leu Tyr Glu Arg Ser His Lys Leu Arg Lys Asn 755 760 765 Asn His His Leu Phe Thr Thr Thr Ile Asn Leu Asn Ser Met Asn Asp 770 775 780 Gly Trp Tyr Gly Ala Leu Lys Glu Ala Ile Gln Gln Gln Gln Asn Gln 785 790 795 800 Leu Val Trp Val Ser Glu Gly Lys Ala Asp Gly Ala Thr Ser Asp Asp 805 810 815 Leu Asp Leu His Asp Asp Arg Leu Ser Tyr Leu Ser Ala Pro Gly Ser 820 825 830 Glu Tyr Ser Met Tyr Ser Thr Asp Ser Arg His Thr Ser Asp Tyr Glu 835 840 845 Asp Thr Asp Thr Glu Gly Gly Ala Tyr Thr Asp Gln Glu Leu Asp Glu 850 855 860 Thr Leu Asn Asp Glu Val Gly Thr Pro Pro Glu Ser Ala Ile Thr Arg 865 870 875 880 Ser Ser Glu Pro Val Arg Glu Asp Ser Ser Gly Met His His Glu Asn 885 890 895 Gln Thr Tyr Pro Pro Tyr Ser Pro Gln Ala Gln Pro Gln Pro Ile His 900 905 910 Arg Ile Asp Ser Pro Gly Phe Lys Pro Ala Ser Gln Gln Val Tyr Arg 915 920 925 Lys Asp Pro Tyr Pro Glu Glu Met Met Arg Gln Asn His Val Leu Lys 930 935 940 Gln Pro Ala Val Ser His Pro Gly His Arg Pro Asp Lys Glu Pro Asn 945 950 955 960 Leu Thr Tyr Glu Pro Gln Leu Pro Tyr Val Glu Lys Gln Ala Ser Arg 965 970 975 Asp Leu Glu Gln Pro Thr Tyr Arg Tyr Glu Ser Ser Ser Tyr Thr Asp 980 985 990 Gln Phe Ser Arg Asn Tyr Glu His Arg Leu Arg Tyr Glu Asp Arg Val 995 1000 1005 Pro Met Tyr Glu Glu Gln Trp Ser Tyr Tyr Asp Asp Lys Gln Pro 1010 1015 1020 Tyr Pro Ser Arg Pro Pro Phe Asp Asn Gln His Ser Gln Asp Leu 1025 1030 1035 Asp Ser Arg Gln His Pro Glu Glu Ser Ser Glu Arg Gly Tyr Phe 1040 1045 1050 Pro Arg Phe Glu Glu Pro Ala Pro Leu Ser Tyr Asp Ser Arg Pro 1055 1060 1065 Arg Tyr Glu Gln Ala Pro Arg Ala Ser Ala Leu Arg His Glu Glu 1070 1075 1080 Gln Pro Ala Pro Gly Tyr Asp Thr His Gly Arg Leu Arg Pro Glu 1085 1090 1095 Ala Gln Pro His Pro Ser Ala Gly Pro Lys Pro Ala Glu Ser Lys 1100 1105 1110 Gln Tyr Phe Glu Gln Tyr Ser Arg Ser Tyr Glu Gln Val Pro Pro 1115 1120 1125 Gln Gly Phe Thr Ser Arg Ala Gly His Phe Glu Pro Leu His Gly 1130 1135 1140 Ala Ala Ala Val Pro Pro Leu Ile Pro Ser Ser Gln His Lys Pro 1145 1150 1155 Glu Ala Leu Pro Ser Asn Thr Lys Pro Leu Pro Pro Pro Pro Thr 1160 1165 1170 Gln Thr Glu Glu Glu Glu Asp Pro Ala Met Lys Pro Gln Ser Val 1175 1180 1185 Leu Thr Arg Val Lys Met Phe Glu Asn Lys Arg Ser Ala Ser Leu 1190 1195 1200 Glu Thr Lys Lys Asp Val Asn Asp Thr Gly Ser Phe Lys Pro Pro 1205 1210 1215 Glu Val Ala Ser Lys Pro Ser Gly Ala Pro Ile Ile Gly Pro Lys 1220 1225 1230 Pro Thr Ser Gln Asn Gln Phe Ser Glu His Asp Lys Thr Leu Tyr 1235 1240 1245 Arg Ile Pro Glu Pro Gln Lys Pro Gln Leu Lys Pro Pro Glu Asp 1250 1255 1260 Ile Val Arg Ser Asn His Tyr Asp Pro Glu Glu Asp Glu Glu Tyr 1265 1270 1275 Tyr Arg Lys Gln Leu Ser Tyr Phe Asp Arg Arg Ser Phe Glu Asn 1280 1285 1290 Lys Pro Pro Ala His Ile Ala Ala Ser His Leu Ser Glu Pro Ala 1295 1300 1305 Lys Pro Ala His Ser Gln Asn Gln Ser Asn Phe Ser Ser Tyr Ser 1310 1315 1320 Ser Lys Gly Lys Pro Pro Glu Ala Asp Gly Val Asp Arg Ser Phe 1325 1330 1335 Gly Glu Lys Arg Tyr Glu Pro Ile Gln Ala Thr Pro Pro Pro Pro 1340 1345 1350 Pro Leu Pro Ser Gln Tyr Ala Gln Pro Ser Gln Pro Val Thr Ser 1355 1360 1365 Ala Ser Leu His Ile His Ser Lys Gly Ala His Gly Glu Gly Asn 1370 1375 1380 Ser Val Ser Leu Asp Phe Gln Asn Ser Leu Val Ser Lys Pro Asp 1385 1390 1395 Pro Pro Pro Ser Gln Asn Lys Pro Ala Thr Phe Arg Pro Pro Asn 1400 1405 1410 Arg Glu Asp Thr Ala Gln Ala Ala Phe Tyr Pro Gln Lys Ser Phe 1415 1420 1425 Pro Asp Lys Ala Pro Val Asn Gly Thr Glu Gln Thr Gln Lys Thr 1430 1435 1440 Val Thr Pro Ala Tyr Asn Arg Phe Thr Pro Lys Pro Tyr Thr Ser 1445 1450 1455 Ser Ala Arg Pro Phe Glu Arg Lys Phe Glu Ser Pro Lys Phe Asn 1460 1465 1470 His Asn Leu Leu Pro Ser Glu Thr Ala His Lys Pro Asp Leu Ser 1475 1480 1485 Ser Lys Thr Pro Thr Ser Pro Lys Thr Leu Val Lys Ser His Ser 1490 1495 1500 Leu Ala Gln Pro Pro Glu Phe Asp Ser Gly Val Glu Thr Phe Ser 1505 1510 1515 Ile His Ala Glu Lys Pro Lys Tyr Gln Ile Asn Asn Ile Ser Thr 1520 1525 1530 Val Pro Lys Ala Ile Pro Val Ser Pro Ser Ala Val Glu Glu Asp 1535 1540 1545 Glu Asp Glu Asp Gly His Thr Val Val Ala Thr Ala Arg Gly Ile 1550 1555 1560 Phe Asn Ser Asn Gly Gly Val Leu Ser Ser Ile Glu Thr Gly Val 1565 1570 1575 Ser Ile Ile Ile Pro Gln Gly Ala Ile Pro Glu Gly Val Glu Gln 1580 1585 1590 Glu Ile Tyr Phe Lys Val Cys Arg Asp Asn Ser Ile Leu Pro Pro 1595 1600 1605 Leu Asp Lys Glu Lys Gly Glu Thr Leu Leu Ser Pro Leu Val Met 1610 1615 1620 Cys Gly Pro His Gly Leu Lys Phe Leu Lys Pro Val Glu Leu Arg 1625 1630 1635 Leu Pro His Cys Ala Ser Met Thr Pro Asp Gly Trp Ser Phe Ala 1640 1645 1650 Leu Lys Ser Ser Asp Ser Ser Ser Gly Asp Pro Lys Thr Trp Gln 1655 1660 1665 Asn Lys Cys Leu Pro Gly Asp Pro Asn Tyr Leu Val Gly Ala Asn 1670 1675 1680 Cys Val Ser Val Leu Ile Asp His Phe 1685 1690 <![CDATA[<210> 156]]> <![CDATA[<211> 1768]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 156]]> Met Ser Ala Arg Ala Ala Ala Ala Lys Ser Thr Ala Met Glu Glu Thr 1 5 10 15 Ala Ile Trp Glu Gln His Thr Val Thr Leu His Arg Ala Pro Gly Phe 20 25 30 Gly Phe Gly Ile Ala Ile Ser Gly Gly Arg Asp Asn Pro His Phe Gln 35 40 45 Ser Gly Glu Thr Ser Ile Val Ile Ser Asp Val Leu Lys Gly Gly Pro 50 55 60 Ala Glu Gly Gln Leu Gln Glu Asn Asp Arg Val Ala Met Val Asn Gly 65 70 75 80 Val Ser Met Asp Asn Val Glu His Ala Phe Ala Val Gln Gln Leu Arg 85 90 95 Lys Ser Gly Lys Asn Ala Lys Ile Thr Ile Arg Arg Lys Lys Lys Val 100 105 110 Gln Ile Pro Val Ser Arg Pro Asp Pro Glu Pro Val Ser Asp Asn Glu 115 120 125 Glu Asp Ser Tyr Asp Glu Glu Ile His Asp Pro Arg Ser Gly Arg Ser 130 135 140 Gly Val Val Asn Arg Arg Ser Glu Lys Ile Trp Pro Arg Asp Arg Ser 145 150 155 160 Ala Ser Arg Glu Arg Ser Leu Ser Pro Arg Ser Asp Arg Arg Ser Val 165 170 175 Ala Ser Ser Gln Pro Ala Lys Pro Thr Lys Val Thr Leu Val Lys Ser 180 185 190 Arg Lys Asn Glu Glu Tyr Gly Leu Arg Leu Ala Ser His Ile Phe Val 195 200 205 Lys Glu Ile Ser Gln Asp Ser Leu Ala Ala Arg Asp Gly Asn Ile Gln 210 215 220 Glu Gly Asp Val Val Leu Lys Ile Asn Gly Thr Val Thr Glu Asn Met 225 230 235 240 Ser Leu Thr Asp Ala Lys Thr Leu Ile Glu Arg Ser Lys Gly Lys Leu 245 250 255 Lys Met Val Val Gln Arg Asp Glu Arg Ala Thr Leu Leu Asn Val Pro 260 265 270 Asp Leu Ser Asp Ser Ile His Ser Ala Asn Ala Ser Glu Arg Asp Asp 275 280 285 Ile Ser Glu Ile Gln Ser Leu Ala Ser Asp His Ser Gly Arg Ser His 290 295 300 Asp Arg Pro Pro Arg Arg Ser Arg Ser Arg Ser Pro Asp Gln Arg Ser 305 310 315 320 Glu Pro Ser Asp His Ser Arg His Ser Pro Gln Gln Pro Ser Asn Gly 325 330 335 Ser Leu Arg Ser Arg Asp Glu Glu Arg Ile Ser Lys Pro Gly Ala Val 340 345 350 Ser Thr Pro Val Lys His Ala Asp Asp His Thr Pro Lys Thr Val Glu 355 360 365 Glu Val Thr Val Glu Arg Asn Glu Lys Gln Thr Pro Ser Leu Pro Glu 370 375 380 Pro Lys Pro Val Tyr Ala Gln Val Gly Gln Pro Asp Val Asp Leu Pro 385 390 395 400 Val Ser Pro Ser Asp Gly Val Leu Pro Asn Ser Thr His Glu Asp Gly 405 410 415 Ile Leu Arg Pro Ser Met Lys Leu Val Lys Phe Arg Lys Gly Asp Ser 420 425 430 Val Gly Leu Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val Ala 435 440 445 Gly Val Leu Glu Asp Ser Pro Ala Ala Lys Glu Gly Leu Glu Glu Gly 450 455 460 Asp Gln Ile Leu Arg Val Asn Asn Val Asp Phe Thr Asn Ile Ile Arg 465 470 475 480 Glu Glu Ala Val Leu Phe Leu Leu Asp Leu Pro Lys Gly Glu Glu Val 485 490 495 Thr Ile Leu Ala Gln Lys Lys Lys Asp Val Tyr Arg Arg Ile Val Glu 500 505 510 Ser Asp Val Gly Asp Ser Phe Tyr Ile Arg Thr His Phe Glu Tyr Glu 515 520 525 Lys Glu Ser Pro Tyr Gly Leu Ser Phe Asn Lys Gly Glu Val Phe Arg 530 535 540 Val Val Asp Thr Leu Tyr Asn Gly Lys Leu Gly Ser Trp Leu Ala Ile 545 550 555 560 Arg Ile Gly Lys Asn His Lys Glu Val Glu Arg Gly Ile Ile Pro Asn 565 570 575 Lys Asn Arg Ala Glu Gln Leu Ala Ser Val Gln Tyr Thr Leu Pro Lys 580 585 590 Thr Ala Gly Gly Asp Arg Ala Asp Phe Trp Arg Phe Arg Gly Leu Arg 595 600 605 Ser Ser Lys Arg Asn Leu Arg Lys Ser Arg Glu Asp Leu Ser Ala Gln 610 615 620 Pro Val Gln Thr Lys Phe Pro Ala Tyr Glu Arg Val Val Leu Arg Glu 625 630 635 640 Ala Gly Phe Leu Arg Pro Val Thr Ile Phe Gly Pro Ile Ala Asp Val 645 650 655 Ala Arg Glu Lys Leu Ala Arg Glu Glu Pro Asp Ile Tyr Gln Ile Ala 660 665 670 Lys Ser Glu Pro Arg Asp Ala Gly Thr Asp Gln Arg Ser Ser Gly Ile 675 680 685 Ile Arg Leu His Thr Ile Lys Gln Ile Ile Asp Gln Asp Lys His Ala 690 695 700 Leu Leu Asp Val Thr Pro Asn Ala Val Asp Arg Leu Asn Tyr Ala Gln 705 710 715 720 Trp Tyr Pro Ile Val Val Phe Leu Asn Pro Asp Ser Lys Gln Gly Val 725 730 735 Lys Thr Met Arg Met Arg Leu Cys Pro Glu Ser Arg Lys Ser Ala Arg 740 745 750 Lys Leu Tyr Glu Arg Ser His Lys Leu Arg Lys Asn Asn His His Leu 755 760 765 Phe Thr Thr Thr Ile Asn Leu Asn Ser Met Asn Asp Gly Trp Tyr Gly 770 775 780 Ala Leu Lys Glu Ala Ile Gln Gln Gln Gln Asn Gln Leu Val Trp Val 785 790 795 800 Ser Glu Gly Lys Ala Asp Gly Ala Thr Ser Asp Asp Leu Asp Leu His 805 810 815 Asp Asp Arg Leu Ser Tyr Leu Ser Ala Pro Gly Ser Glu Tyr Ser Met 820 825 830 Tyr Ser Thr Asp Ser Arg His Thr Ser Asp Tyr Glu Asp Thr Asp Thr 835 840 845 Glu Gly Gly Ala Tyr Thr Asp Gln Glu Leu Asp Glu Thr Leu Asn Asp 850 855 860 Glu Val Gly Thr Pro Pro Glu Ser Ala Ile Thr Arg Ser Ser Glu Pro 865 870 875 880 Val Arg Glu Asp Ser Ser Gly Met His His Glu Asn Gln Thr Tyr Pro 885 890 895 Pro Tyr Ser Pro Gln Ala Gln Pro Gln Pro Ile His Arg Ile Asp Ser 900 905 910 Pro Gly Phe Lys Pro Ala Ser Gln Gln Lys Ala Glu Ala Ser Ser Pro 915 920 925 Val Pro Tyr Leu Ser Pro Glu Thr Asn Pro Ala Ser Ser Thr Ser Ala 930 935 940 Val Asn His Asn Val Asn Leu Thr Asn Val Arg Leu Glu Glu Pro Thr 945 950 955 960 Pro Ala Pro Ser Thr Ser Tyr Ser Pro Gln Ala Asp Ser Leu Arg Thr 965 970 975 Pro Ser Thr Glu Ala Ala His Ile Met Leu Arg Asp Gln Glu Pro Ser 980 985 990 Leu Ser Ser His Val Asp Pro Thr Lys Val Tyr Arg Lys Asp Pro Tyr 995 1000 1005 Pro Glu Glu Met Met Arg Gln Asn His Val Leu Lys Gln Pro Ala 1010 1015 1020 Val Ser His Pro Gly His Arg Pro Asp Lys Glu Pro Asn Leu Thr 1025 1030 1035 Tyr Glu Pro Gln Leu Pro Tyr Val Glu Lys Gln Ala Ser Arg Asp 1040 1045 1050 Leu Glu Gln Pro Thr Tyr Arg Tyr Glu Ser Ser Ser Tyr Thr Asp 1055 1060 1065 Gln Phe Ser Arg Asn Tyr Glu His Arg Leu Arg Tyr Glu Asp Arg 1070 1075 1080 Val Pro Met Tyr Glu Glu Gln Trp Ser Tyr Tyr Asp Asp Lys Gln 1085 1090 1095 Pro Tyr Pro Ser Arg Pro Pro Phe Asp Asn Gln His Ser Gln Asp 1100 1105 1110 Leu Asp Ser Arg Gln His Pro Glu Glu Ser Ser Glu Arg Gly Tyr 1115 1120 1125 Phe Pro Arg Phe Glu Glu Pro Ala Pro Leu Ser Tyr Asp Ser Arg 1130 1135 1140 Pro Arg Tyr Glu Gln Ala Pro Arg Ala Ser Ala Leu Arg His Glu 1145 1150 1155 Glu Gln Pro Ala Pro Gly Tyr Asp Thr His Gly Arg Leu Arg Pro 1160 1165 1170 Glu Ala Gln Pro His Pro Ser Ala Gly Pro Lys Pro Ala Glu Ser 1175 1180 1185 Lys Gln Tyr Phe Glu Gln Tyr Ser Arg Ser Tyr Glu Gln Val Pro 1190 1195 1200 Pro Gln Gly Phe Thr Ser Arg Ala Gly His Phe Glu Pro Leu His 1205 1210 1215 Gly Ala Ala Ala Val Pro Pro Leu Ile Pro Ser Ser Gln His Lys 1220 1225 1230 Pro Glu Ala Leu Pro Ser Asn Thr Lys Pro Leu Pro Pro Pro Pro 1235 1240 1245 Thr Gln Thr Glu Glu Glu Glu Asp Pro Ala Met Lys Pro Gln Ser 1250 1255 1260 Val Leu Thr Arg Val Lys Met Phe Glu Asn Lys Arg Ser Ala Ser 1265 1270 1275 Leu Glu Thr Lys Lys Asp Val Asn Asp Thr Gly Ser Phe Lys Pro 1280 1285 1290 Pro Glu Val Ala Ser Lys Pro Ser Gly Ala Pro Ile Ile Gly Pro 1295 1300 1305 Lys Pro Thr Ser Gln Asn Gln Phe Ser Glu His Asp Lys Thr Leu 1310 1315 1320 Tyr Arg Ile Pro Glu Pro Gln Lys Pro Gln Leu Lys Pro Pro Glu 1325 1330 1335 Asp Ile Val Arg Ser Asn His Tyr Asp Pro Glu Glu Asp Glu Glu 1340 1345 1350 Tyr Tyr Arg Lys Gln Leu Ser Tyr Phe Asp Arg Arg Ser Phe Glu 1355 1360 1365 Asn Lys Pro Pro Ala His Ile Ala Ala Ser His Leu Ser Glu Pro 1370 1375 1380 Ala Lys Pro Ala His Ser Gln Asn Gln Ser Asn Phe Ser Ser Tyr 1385 1390 1395 Ser Ser Lys Gly Lys Pro Pro Glu Ala Asp Gly Val Asp Arg Ser 1400 1405 1410 Phe Gly Glu Lys Arg Tyr Glu Pro Ile Gln Ala Thr Pro Pro Pro 1415 1420 1425 Pro Pro Leu Pro Ser Gln Tyr Ala Gln Pro Ser Gln Pro Val Thr 1430 1435 1440 Ser Ala Ser Leu His Ile His Ser Lys Gly Ala His Gly Glu Gly 1445 1450 1455 Asn Ser Val Ser Leu Asp Phe Gln Asn Ser Leu Val Ser Lys Pro 1460 1465 1470 Asp Pro Pro Pro Ser Gln Asn Lys Pro Ala Thr Phe Arg Pro Pro 1475 1480 1485 Asn Arg Glu Asp Thr Ala Gln Ala Ala Phe Tyr Pro Gln Lys Ser 1490 1495 1500 Phe Pro Asp Lys Ala Pro Val Asn Gly Thr Glu Gln Thr Gln Lys 1505 1510 1515 Thr Val Thr Pro Ala Tyr Asn Arg Phe Thr Pro Lys Pro Tyr Thr 1520 1525 1530 Ser Ser Ala Arg Pro Phe Glu Arg Lys Phe Glu Ser Pro Lys Phe 1535 1540 1545 Asn His Asn Leu Leu Pro Ser Glu Thr Ala His Lys Pro Asp Leu 1550 1555 1560 Ser Ser Lys Thr Pro Thr Ser Pro Lys Thr Leu Val Lys Ser His 1565 1570 1575 Ser Leu Ala Gln Pro Pro Glu Phe Asp Ser Gly Val Glu Thr Phe 1580 1585 1590 Ser Ile His Ala Glu Lys Pro Lys Tyr Gln Ile Asn Asn Ile Ser 1595 1600 1605 Thr Val Pro Lys Ala Ile Pro Val Ser Pro Ser Ala Val Glu Glu 1610 1615 1620 Asp Glu Asp Glu Asp Gly His Thr Val Val Ala Thr Ala Arg Gly 1625 1630 1635 Ile Phe Asn Ser Asn Gly Gly Val Leu Ser Ser Ile Glu Thr Gly 1640 1645 1650 Val Ser Ile Ile Ile Pro Gln Gly Ala Ile Pro Glu Gly Val Glu 1655 1660 1665 Gln Glu Ile Tyr Phe Lys Val Cys Arg Asp Asn Ser Ile Leu Pro 1670 1675 1680 Pro Leu Asp Lys Glu Lys Gly Glu Thr Leu Leu Ser Pro Leu Val 1685 1690 1695 Met Cys Gly Pro His Gly Leu Lys Phe Leu Lys Pro Val Glu Leu 1700 1705 1710 Arg Leu Pro His Cys Ala Ser Met Thr Pro Asp Gly Trp Ser Phe 1715 1720 1725 Ala Leu Lys Ser Ser Asp Ser Ser Ser Gly Asp Pro Lys Thr Trp 1730 1735 1740 Gln Asn Lys Cys Leu Pro Gly Asp Pro Asn Tyr Leu Val Gly Ala 1745 1750 1755 Asn Cys Val Ser Val Leu Ile Asp His Phe 1760 1765 <![CDATA[<210> 157]]> <![CDATA[<211> 1841]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 157]]> Met Arg Arg Leu Glu Gly Leu Cys Leu Arg Arg Arg Arg Arg Arg Arg 1 5 10 15 Gly Pro Ala Arg Glu Arg Ser Gly Asp Lys Met Lys Tyr Gln Lys Tyr 20 25 30 Leu Thr Val Leu Gln Met Ala Ile Gly Val Thr Pro Ser Asn Arg Gly 35 40 45 Ser Leu Leu Pro Leu Lys Arg Lys Leu Trp Val Thr Pro Ser Ser Glu 50 55 60 Asn Pro Asn Gly Ala Thr Ser Ser Val Ser Gln Gly Lys Pro Ser Leu 65 70 75 80 Arg Arg Ile Lys Gly Arg Leu His Arg Ser Lys Ser Leu Asp Ser Met 85 90 95 Asp Phe Cys Glu Leu Thr Ser Thr Ala Met Glu Glu Thr Ala Ile Trp 100 105 110 Glu Gln His Thr Val Thr Leu His Arg Ala Pro Gly Phe Gly Phe Gly 115 120 125 Ile Ala Ile Ser Gly Gly Arg Asp Asn Pro His Phe Gln Ser Gly Glu 130 135 140 Thr Ser Ile Val Ile Ser Asp Val Leu Lys Gly Gly Pro Ala Glu Gly 145 150 155 160 Gln Leu Gln Glu Asn Asp Arg Val Ala Met Val Asn Gly Val Ser Met 165 170 175 Asp Asn Val Glu His Ala Phe Ala Val Gln Gln Leu Arg Lys Ser Gly 180 185 190 Lys Asn Ala Lys Ile Thr Ile Arg Arg Lys Lys Lys Val Gln Ile Pro 195 200 205 Val Ser Arg Pro Asp Pro Glu Pro Val Ser Asp Asn Glu Glu Asp Ser 210 215 220 Tyr Asp Glu Glu Ile His Asp Pro Arg Ser Gly Arg Ser Gly Val Val 225 230 235 240 Asn Arg Arg Ser Glu Lys Ile Trp Pro Arg Asp Arg Ser Ala Ser Arg 245 250 255 Glu Arg Ser Leu Ser Pro Arg Ser Asp Arg Arg Ser Val Ala Ser Ser 260 265 270 Gln Pro Ala Lys Pro Thr Lys Val Thr Leu Val Lys Ser Arg Lys Asn 275 280 285 Glu Glu Tyr Gly Leu Arg Leu Ala Ser His Ile Phe Val Lys Glu Ile 290 295 300 Ser Gln Asp Ser Leu Ala Ala Arg Asp Gly Asn Ile Gln Glu Gly Asp 305 310 315 320 Val Val Leu Lys Ile Asn Gly Thr Val Thr Glu Asn Met Ser Leu Thr 325 330 335 Asp Ala Lys Thr Leu Ile Glu Arg Ser Lys Gly Lys Leu Lys Met Val 340 345 350 Val Gln Arg Asp Glu Arg Ala Thr Leu Leu Asn Val Pro Asp Leu Ser 355 360 365 Asp Ser Ile His Ser Ala Asn Ala Ser Glu Arg Asp Asp Ile Ser Glu 370 375 380 Ile Gln Ser Leu Ala Ser Asp His Ser Gly Arg Ser His Asp Arg Pro 385 390 395 400 Pro Arg Arg Ser Arg Ser Arg Ser Pro Asp Gln Arg Ser Glu Pro Ser 405 410 415 Asp His Ser Arg His Ser Pro Gln Gln Pro Ser Asn Gly Ser Leu Arg 420 425 430 Ser Arg Asp Glu Glu Arg Ile Ser Lys Pro Gly Ala Val Ser Thr Pro 435 440 445 Val Lys His Ala Asp Asp His Thr Pro Lys Thr Val Glu Glu Val Thr 450 455 460 Val Glu Arg Asn Glu Lys Gln Thr Pro Ser Leu Pro Glu Pro Lys Pro 465 470 475 480 Val Tyr Ala Gln Val Gly Gln Pro Asp Val Asp Leu Pro Val Ser Pro 485 490 495 Ser Asp Gly Val Leu Pro Asn Ser Thr His Glu Asp Gly Ile Leu Arg 500 505 510 Pro Ser Met Lys Leu Val Lys Phe Arg Lys Gly Asp Ser Val Gly Leu 515 520 525 Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val Ala Gly Val Leu 530 535 540 Glu Asp Ser Pro Ala Ala Lys Glu Gly Leu Glu Glu Gly Asp Gln Ile 545 550 555 560 Leu Arg Val Asn Asn Val Asp Phe Thr Asn Ile Ile Arg Glu Glu Ala 565 570 575 Val Leu Phe Leu Leu Asp Leu Pro Lys Gly Glu Glu Val Thr Ile Leu 580 585 590 Ala Gln Lys Lys Lys Asp Val Tyr Arg Arg Ile Val Glu Ser Asp Val 595 600 605 Gly Asp Ser Phe Tyr Ile Arg Thr His Phe Glu Tyr Glu Lys Glu Ser 610 615 620 Pro Tyr Gly Leu Ser Phe Asn Lys Gly Glu Val Phe Arg Val Val Asp 625 630 635 640 Thr Leu Tyr Asn Gly Lys Leu Gly Ser Trp Leu Ala Ile Arg Ile Gly 645 650 655 Lys Asn His Lys Glu Val Glu Arg Gly Ile Ile Pro Asn Lys Asn Arg 660 665 670 Ala Glu Gln Leu Ala Ser Val Gln Tyr Thr Leu Pro Lys Thr Ala Gly 675 680 685 Gly Asp Arg Ala Asp Phe Trp Arg Phe Arg Gly Leu Arg Ser Ser Lys 690 695 700 Arg Asn Leu Arg Lys Ser Arg Glu Asp Leu Ser Ala Gln Pro Val Gln 705 710 715 720 Thr Lys Phe Pro Ala Tyr Glu Arg Val Val Leu Arg Glu Ala Gly Phe 725 730 735 Leu Arg Pro Val Thr Ile Phe Gly Pro Ile Ala Asp Val Ala Arg Glu 740 745 750 Lys Leu Ala Arg Glu Glu Pro Asp Ile Tyr Gln Ile Ala Lys Ser Glu 755 760 765 Pro Arg Asp Ala Gly Thr Asp Gln Arg Ser Ser Gly Ile Ile Arg Leu 770 775 780 His Thr Ile Lys Gln Ile Ile Asp Gln Asp Lys His Ala Leu Leu Asp 785 790 795 800 Val Thr Pro Asn Ala Val Asp Arg Leu Asn Tyr Ala Gln Trp Tyr Pro 805 810 815 Ile Val Val Phe Leu Asn Pro Asp Ser Lys Gln Gly Val Lys Thr Met 820 825 830 Arg Met Arg Leu Cys Pro Glu Ser Arg Lys Ser Ala Arg Lys Leu Tyr 835 840 845 Glu Arg Ser His Lys Leu Arg Lys Asn Asn His His Leu Phe Thr Thr 850 855 860 Thr Ile Asn Leu Asn Ser Met Asn Asp Gly Trp Tyr Gly Ala Leu Lys 865 870 875 880 Glu Ala Ile Gln Gln Gln Gln Asn Gln Leu Val Trp Val Ser Glu Gly 885 890 895 Lys Ala Asp Gly Ala Thr Ser Asp Asp Leu Asp Leu His Asp Asp Arg 900 905 910 Leu Ser Tyr Leu Ser Ala Pro Gly Ser Glu Tyr Ser Met Tyr Ser Thr 915 920 925 Asp Ser Arg His Thr Ser Asp Tyr Glu Asp Thr Asp Thr Glu Gly Gly 930 935 940 Ala Tyr Thr Asp Gln Glu Leu Asp Glu Thr Leu Asn Asp Glu Val Gly 945 950 955 960 Thr Pro Pro Glu Ser Ala Ile Thr Arg Ser Ser Glu Pro Val Arg Glu 965 970 975 Asp Ser Ser Gly Met His His Glu Asn Gln Thr Tyr Pro Pro Tyr Ser 980 985 990 Pro Gln Ala Gln Pro Gln Pro Ile His Arg Ile Asp Ser Pro Gly Phe 995 1000 1005 Lys Pro Ala Ser Gln Gln Lys Ala Glu Ala Ser Ser Pro Val Pro 1010 1015 1020 Tyr Leu Ser Pro Glu Thr Asn Pro Ala Ser Ser Thr Ser Ala Val 1025 1030 1035 Asn His Asn Val Asn Leu Thr Asn Val Arg Leu Glu Glu Pro Thr 1040 1045 1050 Pro Ala Pro Ser Thr Ser Tyr Ser Pro Gln Ala Asp Ser Leu Arg 1055 1060 1065 Thr Pro Ser Thr Glu Ala Ala His Ile Met Leu Arg Asp Gln Glu 1070 1075 1080 Pro Ser Leu Ser Ser His Val Asp Pro Thr Lys Val Tyr Arg Lys 1085 1090 1095 Asp Pro Tyr Pro Glu Glu Met Met Arg Gln Asn His Val Leu Lys 1100 1105 1110 Gln Pro Ala Val Ser His Pro Gly His Arg Pro Asp Lys Glu Pro 1115 1120 1125 Asn Leu Thr Tyr Glu Pro Gln Leu Pro Tyr Val Glu Lys Gln Ala 1130 1135 1140 Ser Arg Asp Leu Glu Gln Pro Thr Tyr Arg Tyr Glu Ser Ser Ser 1145 1150 1155 Tyr Thr Asp Gln Phe Ser Arg Asn Tyr Glu His Arg Leu Arg Tyr 1160 1165 1170 Glu Asp Arg Val Pro Met Tyr Glu Glu Gln Trp Ser Tyr Tyr Asp 1175 1180 1185 Asp Lys Gln Pro Tyr Pro Ser Arg Pro Pro Phe Asp Asn Gln His 1190 1195 1200 Ser Gln Asp Leu Asp Ser Arg Gln His Pro Glu Glu Ser Ser Glu 1205 1210 1215 Arg Gly Tyr Phe Pro Arg Phe Glu Glu Pro Ala Pro Leu Ser Tyr 1220 1225 1230 Asp Ser Arg Pro Arg Tyr Glu Gln Ala Pro Arg Ala Ser Ala Leu 1235 1240 1245 Arg His Glu Glu Gln Pro Ala Pro Gly Tyr Asp Thr His Gly Arg 1250 1255 1260 Leu Arg Pro Glu Ala Gln Pro His Pro Ser Ala Gly Pro Lys Pro 1265 1270 1275 Ala Glu Ser Lys Gln Tyr Phe Glu Gln Tyr Ser Arg Ser Tyr Glu 1280 1285 1290 Gln Val Pro Pro Gln Gly Phe Thr Ser Arg Ala Gly His Phe Glu 1295 1300 1305 Pro Leu His Gly Ala Ala Ala Val Pro Pro Leu Ile Pro Ser Ser 1310 1315 1320 Gln His Lys Pro Glu Ala Leu Pro Ser Asn Thr Lys Pro Leu Pro 1325 1330 1335 Pro Pro Pro Thr Gln Thr Glu Glu Glu Glu Asp Pro Ala Met Lys 1340 1345 1350 Pro Gln Ser Val Leu Thr Arg Val Lys Met Phe Glu Asn Lys Arg 1355 1360 1365 Ser Ala Ser Leu Glu Thr Lys Lys Asp Val Asn Asp Thr Gly Ser 1370 1375 1380 Phe Lys Pro Pro Glu Val Ala Ser Lys Pro Ser Gly Ala Pro Ile 1385 1390 1395 Ile Gly Pro Lys Pro Thr Ser Gln Asn Gln Phe Ser Glu His Asp 1400 1405 1410 Lys Thr Leu Tyr Arg Ile Pro Glu Pro Gln Lys Pro Gln Leu Lys 1415 1420 1425 Pro Pro Glu Asp Ile Val Arg Ser Asn His Tyr Asp Pro Glu Glu 1430 1435 1440 Asp Glu Glu Tyr Tyr Arg Lys Gln Leu Ser Tyr Phe Asp Arg Arg 1445 1450 1455 Ser Phe Glu Asn Lys Pro Pro Ala His Ile Ala Ala Ser His Leu 1460 1465 1470 Ser Glu Pro Ala Lys Pro Ala His Ser Gln Asn Gln Ser Asn Phe 1475 1480 1485 Ser Ser Tyr Ser Ser Lys Gly Lys Pro Pro Glu Ala Asp Gly Val 1490 1495 1500 Asp Arg Ser Phe Gly Glu Lys Arg Tyr Glu Pro Ile Gln Ala Thr 1505 1510 1515 Pro Pro Pro Pro Pro Leu Pro Ser Gln Tyr Ala Gln Pro Ser Gln 1520 1525 1530 Pro Val Thr Ser Ala Ser Leu His Ile His Ser Lys Gly Ala His 1535 1540 1545 Gly Glu Gly Asn Ser Val Ser Leu Asp Phe Gln Asn Ser Leu Val 1550 1555 1560 Ser Lys Pro Asp Pro Pro Pro Ser Gln Asn Lys Pro Ala Thr Phe 1565 1570 1575 Arg Pro Pro Asn Arg Glu Asp Thr Ala Gln Ala Ala Phe Tyr Pro 1580 1585 1590 Gln Lys Ser Phe Pro Asp Lys Ala Pro Val Asn Gly Thr Glu Gln 1595 1600 1605 Thr Gln Lys Thr Val Thr Pro Ala Tyr Asn Arg Phe Thr Pro Lys 1610 1615 1620 Pro Tyr Thr Ser Ser Ala Arg Pro Phe Glu Arg Lys Phe Glu Ser 1625 1630 1635 Pro Lys Phe Asn His Asn Leu Leu Pro Ser Glu Thr Ala His Lys 1640 1645 1650 Pro Asp Leu Ser Ser Lys Thr Pro Thr Ser Pro Lys Thr Leu Val 1655 1660 1665 Lys Ser His Ser Leu Ala Gln Pro Pro Glu Phe Asp Ser Gly Val 1670 1675 1680 Glu Thr Phe Ser Ile His Ala Glu Lys Pro Lys Tyr Gln Ile Asn 1685 1690 1695 Asn Ile Ser Thr Val Pro Lys Ala Ile Pro Val Ser Pro Ser Ala 1700 1705 1710 Val Glu Glu Asp Glu Asp Glu Asp Gly His Thr Val Val Ala Thr 1715 1720 1725 Ala Arg Gly Ile Phe Asn Ser Asn Gly Gly Val Leu Ser Ser Ile 1730 1735 1740 Glu Thr Gly Val Ser Ile Ile Ile Pro Gln Gly Ala Ile Pro Glu 1745 1750 1755 Gly Val Glu Gln Glu Ile Tyr Phe Lys Val Cys Arg Asp Asn Ser 1760 1765 1770 Ile Leu Pro Pro Leu Asp Lys Glu Lys Gly Glu Thr Leu Leu Ser 1775 1780 1785 Pro Leu Val Met Cys Gly Pro His Gly Leu Lys Phe Leu Lys Pro 1790 1795 1800 Val Glu Leu Arg Leu Pro His Cys Asp Pro Lys Thr Trp Gln Asn 1805 1810 1815 Lys Cys Leu Pro Gly Asp Pro Asn Tyr Leu Val Gly Ala Asn Cys 1820 1825 1830 Val Ser Val Leu Ile Asp His Phe 1835 1840 <![CDATA[<210> 158]]> <![CDATA[<211> 1759]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 158]]> Met Glu Arg Asn Thr Phe Ser Met Asp Cys His Ser Lys Ser Thr Ala 1 5 10 15 Met Glu Glu Thr Ala Ile Trp Glu Gln His Thr Val Thr Leu His Arg 20 25 30 Ala Pro Gly Phe Gly Phe Gly Ile Ala Ile Ser Gly Gly Arg Asp Asn 35 40 45 Pro His Phe Gln Ser Gly Glu Thr Ser Ile Val Ile Ser Asp Val Leu 50 55 60 Lys Gly Gly Pro Ala Glu Gly Gln Leu Gln Glu Asn Asp Arg Val Ala 65 70 75 80 Met Val Asn Gly Val Ser Met Asp Asn Val Glu His Ala Phe Ala Val 85 90 95 Gln Gln Leu Arg Lys Ser Gly Lys Asn Ala Lys Ile Thr Ile Arg Arg 100 105 110 Lys Lys Lys Val Gln Ile Pro Val Ser Arg Pro Asp Pro Glu Pro Val 115 120 125 Ser Asp Asn Glu Glu Asp Ser Tyr Asp Glu Glu Ile His Asp Pro Arg 130 135 140 Ser Gly Arg Ser Gly Val Val Asn Arg Arg Ser Glu Lys Ile Trp Pro 145 150 155 160 Arg Asp Arg Ser Ala Ser Arg Glu Arg Ser Leu Ser Pro Arg Ser Asp 165 170 175 Arg Arg Ser Val Ala Ser Ser Gln Pro Ala Lys Pro Thr Lys Val Thr 180 185 190 Leu Val Lys Ser Arg Lys Asn Glu Glu Tyr Gly Leu Arg Leu Ala Ser 195 200 205 His Ile Phe Val Lys Glu Ile Ser Gln Asp Ser Leu Ala Ala Arg Asp 210 215 220 Gly Asn Ile Gln Glu Gly Asp Val Val Leu Lys Ile Asn Gly Thr Val 225 230 235 240 Thr Glu Asn Met Ser Leu Thr Asp Ala Lys Thr Leu Ile Glu Arg Ser 245 250 255 Lys Gly Lys Leu Lys Met Val Val Gln Arg Asp Glu Arg Ala Thr Leu 260 265 270 Leu Asn Val Pro Asp Leu Ser Asp Ser Ile His Ser Ala Asn Ala Ser 275 280 285 Glu Arg Asp Asp Ile Ser Glu Ile Gln Ser Leu Ala Ser Asp His Ser 290 295 300 Gly Arg Ser His Asp Arg Pro Pro Arg Arg Ser Arg Ser Arg Ser Pro 305 310 315 320 Asp Gln Arg Ser Glu Pro Ser Asp His Ser Arg His Ser Pro Gln Gln 325 330 335 Pro Ser Asn Gly Ser Leu Arg Ser Arg Asp Glu Glu Arg Ile Ser Lys 340 345 350 Pro Gly Ala Val Ser Thr Pro Val Lys His Ala Asp Asp His Thr Pro 355 360 365 Lys Thr Val Glu Glu Val Thr Val Glu Arg Asn Glu Lys Gln Thr Pro 370 375 380 Ser Leu Pro Glu Pro Lys Pro Val Tyr Ala Gln Val Gly Gln Pro Asp 385 390 395 400 Val Asp Leu Pro Val Ser Pro Ser Asp Gly Val Leu Pro Asn Ser Thr 405 410 415 His Glu Asp Gly Ile Leu Arg Pro Ser Met Lys Leu Val Lys Phe Arg 420 425 430 Lys Gly Asp Ser Val Gly Leu Arg Leu Ala Gly Gly Asn Asp Val Gly 435 440 445 Ile Phe Val Ala Gly Val Leu Glu Asp Ser Pro Ala Ala Lys Glu Gly 450 455 460 Leu Glu Glu Gly Asp Gln Ile Leu Arg Val Asn Asn Val Asp Phe Thr 465 470 475 480 Asn Ile Ile Arg Glu Glu Ala Val Leu Phe Leu Leu Asp Leu Pro Lys 485 490 495 Gly Glu Glu Val Thr Ile Leu Ala Gln Lys Lys Lys Asp Val Tyr Arg 500 505 510 Arg Ile Val Glu Ser Asp Val Gly Asp Ser Phe Tyr Ile Arg Thr His 515 520 525 Phe Glu Tyr Glu Lys Glu Ser Pro Tyr Gly Leu Ser Phe Asn Lys Gly 530 535 540 Glu Val Phe Arg Val Val Asp Thr Leu Tyr Asn Gly Lys Leu Gly Ser 545 550 555 560 Trp Leu Ala Ile Arg Ile Gly Lys Asn His Lys Glu Val Glu Arg Gly 565 570 575 Ile Ile Pro Asn Lys Asn Arg Ala Glu Gln Leu Ala Ser Val Gln Tyr 580 585 590 Thr Leu Pro Lys Thr Ala Gly Gly Asp Arg Ala Asp Phe Trp Arg Phe 595 600 605 Arg Gly Leu Arg Ser Ser Lys Arg Asn Leu Arg Lys Ser Arg Glu Asp 610 615 620 Leu Ser Ala Gln Pro Val Gln Thr Lys Phe Pro Ala Tyr Glu Arg Val 625 630 635 640 Val Leu Arg Glu Ala Gly Phe Leu Arg Pro Val Thr Ile Phe Gly Pro 645 650 655 Ile Ala Asp Val Ala Arg Glu Lys Leu Ala Arg Glu Glu Pro Asp Ile 660 665 670 Tyr Gln Ile Ala Lys Ser Glu Pro Arg Asp Ala Gly Thr Asp Gln Arg 675 680 685 Ser Ser Gly Ile Ile Arg Leu His Thr Ile Lys Gln Ile Ile Asp Gln 690 695 700 Asp Lys His Ala Leu Leu Asp Val Thr Pro Asn Ala Val Asp Arg Leu 705 710 715 720 Asn Tyr Ala Gln Trp Tyr Pro Ile Val Val Phe Leu Asn Pro Asp Ser 725 730 735 Lys Gln Gly Val Lys Thr Met Arg Met Arg Leu Cys Pro Glu Ser Arg 740 745 750 Lys Ser Ala Arg Lys Leu Tyr Glu Arg Ser His Lys Leu Arg Lys Asn 755 760 765 Asn His His Leu Phe Thr Thr Thr Ile Asn Leu Asn Ser Met Asn Asp 770 775 780 Gly Trp Tyr Gly Ala Leu Lys Glu Ala Ile Gln Gln Gln Gln Asn Gln 785 790 795 800 Leu Val Trp Val Ser Glu Gly Lys Ala Asp Gly Ala Thr Ser Asp Asp 805 810 815 Leu Asp Leu His Asp Asp Arg Leu Ser Tyr Leu Ser Ala Pro Gly Ser 820 825 830 Glu Tyr Ser Met Tyr Ser Thr Asp Ser Arg His Thr Ser Asp Tyr Glu 835 840 845 Asp Thr Asp Thr Glu Gly Gly Ala Tyr Thr Asp Gln Glu Leu Asp Glu 850 855 860 Thr Leu Asn Asp Glu Val Gly Thr Pro Pro Glu Ser Ala Ile Thr Arg 865 870 875 880 Ser Ser Glu Pro Val Arg Glu Asp Ser Ser Gly Met His His Glu Asn 885 890 895 Gln Thr Tyr Pro Pro Tyr Ser Pro Gln Ala Gln Pro Gln Pro Ile His 900 905 910 Arg Ile Asp Ser Pro Gly Phe Lys Pro Ala Ser Gln Gln Lys Ala Glu 915 920 925 Ala Ser Ser Pro Val Pro Tyr Leu Ser Pro Glu Thr Asn Pro Ala Ser 930 935 940 Ser Thr Ser Ala Val Asn His Asn Val Asn Leu Thr Asn Val Arg Leu 945 950 955 960 Glu Glu Pro Thr Pro Ala Pro Ser Thr Ser Tyr Ser Pro Gln Ala Asp 965 970 975 Ser Leu Arg Thr Pro Ser Thr Glu Ala Ala His Ile Met Leu Arg Asp 980 985 990 Gln Glu Pro Ser Leu Ser Ser His Val Asp Pro Thr Lys Val Tyr Arg 995 1000 1005 Lys Asp Pro Tyr Pro Glu Glu Met Met Arg Gln Asn His Val Leu 1010 1015 1020 Lys Gln Pro Ala Val Ser His Pro Gly His Arg Pro Asp Lys Glu 1025 1030 1035 Pro Asn Leu Thr Tyr Glu Pro Gln Leu Pro Tyr Val Glu Lys Gln 1040 1045 1050 Ala Ser Arg Asp Leu Glu Gln Pro Thr Tyr Arg Tyr Glu Ser Ser 1055 1060 1065 Ser Tyr Thr Asp Gln Phe Ser Arg Asn Tyr Glu His Arg Leu Arg 1070 1075 1080 Tyr Glu Asp Arg Val Pro Met Tyr Glu Glu Gln Trp Ser Tyr Tyr 1085 1090 1095 Asp Asp Lys Gln Pro Tyr Pro Ser Arg Pro Pro Phe Asp Asn Gln 1100 1105 1110 His Ser Gln Asp Leu Asp Ser Arg Gln His Pro Glu Glu Ser Ser 1115 1120 1125 Glu Arg Gly Tyr Phe Pro Arg Phe Glu Glu Pro Ala Pro Leu Ser 1130 1135 1140 Tyr Asp Ser Arg Pro Arg Tyr Glu Gln Ala Pro Arg Ala Ser Ala 1145 1150 1155 Leu Arg His Glu Glu Gln Pro Ala Pro Gly Tyr Asp Thr His Gly 1160 1165 1170 Arg Leu Arg Pro Glu Ala Gln Pro His Pro Ser Ala Gly Pro Lys 1175 1180 1185 Pro Ala Glu Ser Lys Gln Tyr Phe Glu Gln Tyr Ser Arg Ser Tyr 1190 1195 1200 Glu Gln Val Pro Pro Gln Gly Phe Thr Ser Arg Ala Gly His Phe 1205 1210 1215 Glu Pro Leu His Gly Ala Ala Ala Val Pro Pro Leu Ile Pro Ser 1220 1225 1230 Ser Gln His Lys Pro Glu Ala Leu Pro Ser Asn Thr Lys Pro Leu 1235 1240 1245 Pro Pro Pro Pro Thr Gln Thr Glu Glu Glu Glu Asp Pro Ala Met 1250 1255 1260 Lys Pro Gln Ser Val Leu Thr Arg Val Lys Met Phe Glu Asn Lys 1265 1270 1275 Arg Ser Ala Ser Leu Glu Thr Lys Lys Asp Val Asn Asp Thr Gly 1280 1285 1290 Ser Phe Lys Pro Pro Glu Val Ala Ser Lys Pro Ser Gly Ala Pro 1295 1300 1305 Ile Ile Gly Pro Lys Pro Thr Ser Gln Asn Gln Phe Ser Glu His 1310 1315 1320 Asp Lys Thr Leu Tyr Arg Ile Pro Glu Pro Gln Lys Pro Gln Leu 1325 1330 1335 Lys Pro Pro Glu Asp Ile Val Arg Ser Asn His Tyr Asp Pro Glu 1340 1345 1350 Glu Asp Glu Glu Tyr Tyr Arg Lys Gln Leu Ser Tyr Phe Asp Arg 1355 1360 1365 Arg Ser Phe Glu Asn Lys Pro Pro Ala His Ile Ala Ala Ser His 1370 1375 1380 Leu Ser Glu Pro Ala Lys Pro Ala His Ser Gln Asn Gln Ser Asn 1385 1390 1395 Phe Ser Ser Tyr Ser Ser Lys Gly Lys Pro Pro Glu Ala Asp Gly 1400 1405 1410 Val Asp Arg Ser Phe Gly Glu Lys Arg Tyr Glu Pro Ile Gln Ala 1415 1420 1425 Thr Pro Pro Pro Pro Pro Leu Pro Ser Gln Tyr Ala Gln Pro Ser 1430 1435 1440 Gln Pro Val Thr Ser Ala Ser Leu His Ile His Ser Lys Gly Ala 1445 1450 1455 His Gly Glu Gly Asn Ser Val Ser Leu Asp Phe Gln Asn Ser Leu 1460 1465 1470 Val Ser Lys Pro Asp Pro Pro Pro Ser Gln Asn Lys Pro Ala Thr 1475 1480 1485 Phe Arg Pro Pro Asn Arg Glu Asp Thr Ala Gln Ala Ala Phe Tyr 1490 1495 1500 Pro Gln Lys Ser Phe Pro Asp Lys Ala Pro Val Asn Gly Thr Glu 1505 1510 1515 Gln Thr Gln Lys Thr Val Thr Pro Ala Tyr Asn Arg Phe Thr Pro 1520 1525 1530 Lys Pro Tyr Thr Ser Ser Ala Arg Pro Phe Glu Arg Lys Phe Glu 1535 1540 1545 Ser Pro Lys Phe Asn His Asn Leu Leu Pro Ser Glu Thr Ala His 1550 1555 1560 Lys Pro Asp Leu Ser Ser Lys Thr Pro Thr Ser Pro Lys Thr Leu 1565 1570 1575 Val Lys Ser His Ser Leu Ala Gln Pro Pro Glu Phe Asp Ser Gly 1580 1585 1590 Val Glu Thr Phe Ser Ile His Ala Glu Lys Pro Lys Tyr Gln Ile 1595 1600 1605 Asn Asn Ile Ser Thr Val Pro Lys Ala Ile Pro Val Ser Pro Ser 1610 1615 1620 Ala Val Glu Glu Asp Glu Asp Glu Asp Gly His Thr Val Val Ala 1625 1630 1635 Thr Ala Arg Gly Ile Phe Asn Ser Asn Gly Gly Val Leu Ser Ser 1640 1645 1650 Ile Glu Thr Gly Val Ser Ile Ile Ile Pro Gln Gly Ala Ile Pro 1655 1660 1665 Glu Gly Val Glu Gln Glu Ile Tyr Phe Lys Val Cys Arg Asp Asn 1670 1675 1680 Ser Ile Leu Pro Pro Leu Asp Lys Glu Lys Gly Glu Thr Leu Leu 1685 1690 1695 Ser Pro Leu Val Met Cys Gly Pro His Gly Leu Lys Phe Leu Lys 1700 1705 1710 Pro Val Glu Leu Arg Leu Pro His Cys Ala Ser Met Thr Pro Asp 1715 1720 1725 Gly Asp Pro Lys Thr Trp Gln Asn Lys Cys Leu Pro Gly Asp Pro 1730 1735 1740 Asn Tyr Leu Val Gly Ala Asn Cys Val Ser Val Leu Ile Asp His 1745 1750 1755 Phe <![CDATA[<210> 159]]> <![CDATA[<211> 1755]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 159]]> Met Ser Ala Arg Ala Ala Ala Ala Lys Ser Thr Ala Met Glu Glu Thr 1 5 10 15 Ala Ile Trp Glu Gln His Thr Val Thr Leu His Arg Ala Pro Gly Phe 20 25 30 Gly Phe Gly Ile Ala Ile Ser Gly Gly Arg Asp Asn Pro His Phe Gln 35 40 45 Ser Gly Glu Thr Ser Ile Val Ile Ser Asp Val Leu Lys Gly Gly Pro 50 55 60 Ala Glu Gly Gln Leu Gln Glu Asn Asp Arg Val Ala Met Val Asn Gly 65 70 75 80 Val Ser Met Asp Asn Val Glu His Ala Phe Ala Val Gln Gln Leu Arg 85 90 95 Lys Ser Gly Lys Asn Ala Lys Ile Thr Ile Arg Arg Lys Lys Lys Val 100 105 110 Gln Ile Pro Val Ser Arg Pro Asp Pro Glu Pro Val Ser Asp Asn Glu 115 120 125 Glu Asp Ser Tyr Asp Glu Glu Ile His Asp Pro Arg Ser Gly Arg Ser 130 135 140 Gly Val Val Asn Arg Arg Ser Glu Lys Ile Trp Pro Arg Asp Arg Ser 145 150 155 160 Ala Ser Arg Glu Arg Ser Leu Ser Pro Arg Ser Asp Arg Arg Ser Val 165 170 175 Ala Ser Ser Gln Pro Ala Lys Pro Thr Lys Val Thr Leu Val Lys Ser 180 185 190 Arg Lys Asn Glu Glu Tyr Gly Leu Arg Leu Ala Ser His Ile Phe Val 195 200 205 Lys Glu Ile Ser Gln Asp Ser Leu Ala Ala Arg Asp Gly Asn Ile Gln 210 215 220 Glu Gly Asp Val Val Leu Lys Ile Asn Gly Thr Val Thr Glu Asn Met 225 230 235 240 Ser Leu Thr Asp Ala Lys Thr Leu Ile Glu Arg Ser Lys Gly Lys Leu 245 250 255 Lys Met Val Val Gln Arg Asp Glu Arg Ala Thr Leu Leu Asn Val Pro 260 265 270 Asp Leu Ser Asp Ser Ile His Ser Ala Asn Ala Ser Glu Arg Asp Asp 275 280 285 Ile Ser Glu Ile Gln Ser Leu Ala Ser Asp His Ser Gly Arg Ser His 290 295 300 Asp Arg Pro Pro Arg Arg Ser Arg Ser Arg Ser Pro Asp Gln Arg Ser 305 310 315 320 Glu Pro Ser Asp His Ser Arg His Ser Pro Gln Gln Pro Ser Asn Gly 325 330 335 Ser Leu Arg Ser Arg Asp Glu Glu Arg Ile Ser Lys Pro Gly Ala Val 340 345 350 Ser Thr Pro Val Lys His Ala Asp Asp His Thr Pro Lys Thr Val Glu 355 360 365 Glu Val Thr Val Glu Arg Asn Glu Lys Gln Thr Pro Ser Leu Pro Glu 370 375 380 Pro Lys Pro Val Tyr Ala Gln Val Gly Gln Pro Asp Val Asp Leu Pro 385 390 395 400 Val Ser Pro Ser Asp Gly Val Leu Pro Asn Ser Thr His Glu Asp Gly 405 410 415 Ile Leu Arg Pro Ser Met Lys Leu Val Lys Phe Arg Lys Gly Asp Ser 420 425 430 Val Gly Leu Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val Ala 435 440 445 Gly Val Leu Glu Asp Ser Pro Ala Ala Lys Glu Gly Leu Glu Glu Gly 450 455 460 Asp Gln Ile Leu Arg Val Asn Asn Val Asp Phe Thr Asn Ile Ile Arg 465 470 475 480 Glu Glu Ala Val Leu Phe Leu Leu Asp Leu Pro Lys Gly Glu Glu Val 485 490 495 Thr Ile Leu Ala Gln Lys Lys Lys Asp Val Tyr Arg Arg Ile Val Glu 500 505 510 Ser Asp Val Gly Asp Ser Phe Tyr Ile Arg Thr His Phe Glu Tyr Glu 515 520 525 Lys Glu Ser Pro Tyr Gly Leu Ser Phe Asn Lys Gly Glu Val Phe Arg 530 535 540 Val Val Asp Thr Leu Tyr Asn Gly Lys Leu Gly Ser Trp Leu Ala Ile 545 550 555 560 Arg Ile Gly Lys Asn His Lys Glu Val Glu Arg Gly Ile Ile Pro Asn 565 570 575 Lys Asn Arg Ala Glu Gln Leu Ala Ser Val Gln Tyr Thr Leu Pro Lys 580 585 590 Thr Ala Gly Gly Asp Arg Ala Asp Phe Trp Arg Phe Arg Gly Leu Arg 595 600 605 Ser Ser Lys Arg Asn Leu Arg Lys Ser Arg Glu Asp Leu Ser Ala Gln 610 615 620 Pro Val Gln Thr Lys Phe Pro Ala Tyr Glu Arg Val Val Leu Arg Glu 625 630 635 640 Ala Gly Phe Leu Arg Pro Val Thr Ile Phe Gly Pro Ile Ala Asp Val 645 650 655 Ala Arg Glu Lys Leu Ala Arg Glu Glu Pro Asp Ile Tyr Gln Ile Ala 660 665 670 Lys Ser Glu Pro Arg Asp Ala Gly Thr Asp Gln Arg Ser Ser Gly Ile 675 680 685 Ile Arg Leu His Thr Ile Lys Gln Ile Ile Asp Gln Asp Lys His Ala 690 695 700 Leu Leu Asp Val Thr Pro Asn Ala Val Asp Arg Leu Asn Tyr Ala Gln 705 710 715 720 Trp Tyr Pro Ile Val Val Phe Leu Asn Pro Asp Ser Lys Gln Gly Val 725 730 735 Lys Thr Met Arg Met Arg Leu Cys Pro Glu Ser Arg Lys Ser Ala Arg 740 745 750 Lys Leu Tyr Glu Arg Ser His Lys Leu Arg Lys Asn Asn His His Leu 755 760 765 Phe Thr Thr Thr Ile Asn Leu Asn Ser Met Asn Asp Gly Trp Tyr Gly 770 775 780 Ala Leu Lys Glu Ala Ile Gln Gln Gln Gln Asn Gln Leu Val Trp Val 785 790 795 800 Ser Glu Gly Lys Ala Asp Gly Ala Thr Ser Asp Asp Leu Asp Leu His 805 810 815 Asp Asp Arg Leu Ser Tyr Leu Ser Ala Pro Gly Ser Glu Tyr Ser Met 820 825 830 Tyr Ser Thr Asp Ser Arg His Thr Ser Asp Tyr Glu Asp Thr Asp Thr 835 840 845 Glu Gly Gly Ala Tyr Thr Asp Gln Glu Leu Asp Glu Thr Leu Asn Asp 850 855 860 Glu Val Gly Thr Pro Pro Glu Ser Ala Ile Thr Arg Ser Ser Glu Pro 865 870 875 880 Val Arg Glu Asp Ser Ser Gly Met His His Glu Asn Gln Thr Tyr Pro 885 890 895 Pro Tyr Ser Pro Gln Ala Gln Pro Gln Pro Ile His Arg Ile Asp Ser 900 905 910 Pro Gly Phe Lys Pro Ala Ser Gln Gln Lys Ala Glu Ala Ser Ser Pro 915 920 925 Val Pro Tyr Leu Ser Pro Glu Thr Asn Pro Ala Ser Ser Thr Ser Ala 930 935 940 Val Asn His Asn Val Asn Leu Thr Asn Val Arg Leu Glu Glu Pro Thr 945 950 955 960 Pro Ala Pro Ser Thr Ser Tyr Ser Pro Gln Ala Asp Ser Leu Arg Thr 965 970 975 Pro Ser Thr Glu Ala Ala His Ile Met Leu Arg Asp Gln Glu Pro Ser 980 985 990 Leu Ser Ser His Val Asp Pro Thr Lys Val Tyr Arg Lys Asp Pro Tyr 995 1000 1005 Pro Glu Glu Met Met Arg Gln Asn His Val Leu Lys Gln Pro Ala 1010 1015 1020 Val Ser His Pro Gly His Arg Pro Asp Lys Glu Pro Asn Leu Thr 1025 1030 1035 Tyr Glu Pro Gln Leu Pro Tyr Val Glu Lys Gln Ala Ser Arg Asp 1040 1045 1050 Leu Glu Gln Pro Thr Tyr Arg Tyr Glu Ser Ser Ser Tyr Thr Asp 1055 1060 1065 Gln Phe Ser Arg Asn Tyr Glu His Arg Leu Arg Tyr Glu Asp Arg 1070 1075 1080 Val Pro Met Tyr Glu Glu Gln Trp Ser Tyr Tyr Asp Asp Lys Gln 1085 1090 1095 Pro Tyr Pro Ser Arg Pro Pro Phe Asp Asn Gln His Ser Gln Asp 1100 1105 1110 Leu Asp Ser Arg Gln His Pro Glu Glu Ser Ser Glu Arg Gly Tyr 1115 1120 1125 Phe Pro Arg Phe Glu Glu Pro Ala Pro Leu Ser Tyr Asp Ser Arg 1130 1135 1140 Pro Arg Tyr Glu Gln Ala Pro Arg Ala Ser Ala Leu Arg His Glu 1145 1150 1155 Glu Gln Pro Ala Pro Gly Tyr Asp Thr His Gly Arg Leu Arg Pro 1160 1165 1170 Glu Ala Gln Pro His Pro Ser Ala Gly Pro Lys Pro Ala Glu Ser 1175 1180 1185 Lys Gln Tyr Phe Glu Gln Tyr Ser Arg Ser Tyr Glu Gln Val Pro 1190 1195 1200 Pro Gln Gly Phe Thr Ser Arg Ala Gly His Phe Glu Pro Leu His 1205 1210 1215 Gly Ala Ala Ala Val Pro Pro Leu Ile Pro Ser Ser Gln His Lys 1220 1225 1230 Pro Glu Ala Leu Pro Ser Asn Thr Lys Pro Leu Pro Pro Pro Pro 1235 1240 1245 Thr Gln Thr Glu Glu Glu Glu Asp Pro Ala Met Lys Pro Gln Ser 1250 1255 1260 Val Leu Thr Arg Val Lys Met Phe Glu Asn Lys Arg Ser Ala Ser 1265 1270 1275 Leu Glu Thr Lys Lys Asp Val Asn Asp Thr Gly Ser Phe Lys Pro 1280 1285 1290 Pro Glu Val Ala Ser Lys Pro Ser Gly Ala Pro Ile Ile Gly Pro 1295 1300 1305 Lys Pro Thr Ser Gln Asn Gln Phe Ser Glu His Asp Lys Thr Leu 1310 1315 1320 Tyr Arg Ile Pro Glu Pro Gln Lys Pro Gln Leu Lys Pro Pro Glu 1325 1330 1335 Asp Ile Val Arg Ser Asn His Tyr Asp Pro Glu Glu Asp Glu Glu 1340 1345 1350 Tyr Tyr Arg Lys Gln Leu Ser Tyr Phe Asp Arg Arg Ser Phe Glu 1355 1360 1365 Asn Lys Pro Pro Ala His Ile Ala Ala Ser His Leu Ser Glu Pro 1370 1375 1380 Ala Lys Pro Ala His Ser Gln Asn Gln Ser Asn Phe Ser Ser Tyr 1385 1390 1395 Ser Ser Lys Gly Lys Pro Pro Glu Ala Asp Gly Val Asp Arg Ser 1400 1405 1410 Phe Gly Glu Lys Arg Tyr Glu Pro Ile Gln Ala Thr Pro Pro Pro 1415 1420 1425 Pro Pro Leu Pro Ser Gln Tyr Ala Gln Pro Ser Gln Pro Val Thr 1430 1435 1440 Ser Ala Ser Leu His Ile His Ser Lys Gly Ala His Gly Glu Gly 1445 1450 1455 Asn Ser Val Ser Leu Asp Phe Gln Asn Ser Leu Val Ser Lys Pro 1460 1465 1470 Asp Pro Pro Pro Ser Gln Asn Lys Pro Ala Thr Phe Arg Pro Pro 1475 1480 1485 Asn Arg Glu Asp Thr Ala Gln Ala Ala Phe Tyr Pro Gln Lys Ser 1490 1495 1500 Phe Pro Asp Lys Ala Pro Val Asn Gly Thr Glu Gln Thr Gln Lys 1505 1510 1515 Thr Val Thr Pro Ala Tyr Asn Arg Phe Thr Pro Lys Pro Tyr Thr 1520 1525 1530 Ser Ser Ala Arg Pro Phe Glu Arg Lys Phe Glu Ser Pro Lys Phe 1535 1540 1545 Asn His Asn Leu Leu Pro Ser Glu Thr Ala His Lys Pro Asp Leu 1550 1555 1560 Ser Ser Lys Thr Pro Thr Ser Pro Lys Thr Leu Val Lys Ser His 1565 1570 1575 Ser Leu Ala Gln Pro Pro Glu Phe Asp Ser Gly Val Glu Thr Phe 1580 1585 1590 Ser Ile His Ala Glu Lys Pro Lys Tyr Gln Ile Asn Asn Ile Ser 1595 1600 1605 Thr Val Pro Lys Ala Ile Pro Val Ser Pro Ser Ala Val Glu Glu 1610 1615 1620 Asp Glu Asp Glu Asp Gly His Thr Val Val Ala Thr Ala Arg Gly 1625 1630 1635 Ile Phe Asn Ser Asn Gly Gly Val Leu Ser Ser Ile Glu Thr Gly 1640 1645 1650 Val Ser Ile Ile Ile Pro Gln Gly Ala Ile Pro Glu Gly Val Glu 1655 1660 1665 Gln Glu Ile Tyr Phe Lys Val Cys Arg Asp Asn Ser Ile Leu Pro 1670 1675 1680 Pro Leu Asp Lys Glu Lys Gly Glu Thr Leu Leu Ser Pro Leu Val 1685 1690 1695 Met Cys Gly Pro His Gly Leu Lys Phe Leu Lys Pro Val Glu Leu 1700 1705 1710 Arg Leu Pro His Cys Ala Ser Met Thr Pro Asp Gly Asp Pro Lys 1715 1720 1725 Thr Trp Gln Asn Lys Cys Leu Pro Gly Asp Pro Asn Tyr Leu Val 1730 1735 1740 Gly Ala Asn Cys Val Ser Val Leu Ile Asp His Phe 1745 1750 1755 <![CDATA[<210> 160]]> <![CDATA[<211> 1688]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 160]]> Met Ser Ala Arg Ala Ala Ala Ala Lys Ser Thr Ala Met Glu Glu Thr 1 5 10 15 Ala Ile Trp Glu Gln His Thr Val Thr Leu His Arg Ala Pro Gly Phe 20 25 30 Gly Phe Gly Ile Ala Ile Ser Gly Gly Arg Asp Asn Pro His Phe Gln 35 40 45 Ser Gly Glu Thr Ser Ile Val Ile Ser Asp Val Leu Lys Gly Gly Pro 50 55 60 Ala Glu Gly Gln Leu Gln Glu Asn Asp Arg Val Ala Met Val Asn Gly 65 70 75 80 Val Ser Met Asp Asn Val Glu His Ala Phe Ala Val Gln Gln Leu Arg 85 90 95 Lys Ser Gly Lys Asn Ala Lys Ile Thr Ile Arg Arg Lys Lys Lys Val 100 105 110 Gln Ile Pro Val Ser Arg Pro Asp Pro Glu Pro Val Ser Asp Asn Glu 115 120 125 Glu Asp Ser Tyr Asp Glu Glu Ile His Asp Pro Arg Ser Gly Arg Ser 130 135 140 Gly Val Val Asn Arg Arg Ser Glu Lys Ile Trp Pro Arg Asp Arg Ser 145 150 155 160 Ala Ser Arg Glu Arg Ser Leu Ser Pro Arg Ser Asp Arg Arg Ser Val 165 170 175 Ala Ser Ser Gln Pro Ala Lys Pro Thr Lys Val Thr Leu Val Lys Ser 180 185 190 Arg Lys Asn Glu Glu Tyr Gly Leu Arg Leu Ala Ser His Ile Phe Val 195 200 205 Lys Glu Ile Ser Gln Asp Ser Leu Ala Ala Arg Asp Gly Asn Ile Gln 210 215 220 Glu Gly Asp Val Val Leu Lys Ile Asn Gly Thr Val Thr Glu Asn Met 225 230 235 240 Ser Leu Thr Asp Ala Lys Thr Leu Ile Glu Arg Ser Lys Gly Lys Leu 245 250 255 Lys Met Val Val Gln Arg Asp Glu Arg Ala Thr Leu Leu Asn Val Pro 260 265 270 Asp Leu Ser Asp Ser Ile His Ser Ala Asn Ala Ser Glu Arg Asp Asp 275 280 285 Ile Ser Glu Ile Gln Ser Leu Ala Ser Asp His Ser Gly Arg Ser His 290 295 300 Asp Arg Pro Pro Arg Arg Ser Arg Ser Arg Ser Pro Asp Gln Arg Ser 305 310 315 320 Glu Pro Ser Asp His Ser Arg His Ser Pro Gln Gln Pro Ser Asn Gly 325 330 335 Ser Leu Arg Ser Arg Asp Glu Glu Arg Ile Ser Lys Pro Gly Ala Val 340 345 350 Ser Thr Pro Val Lys His Ala Asp Asp His Thr Pro Lys Thr Val Glu 355 360 365 Glu Val Thr Val Glu Arg Asn Glu Lys Gln Thr Pro Ser Leu Pro Glu 370 375 380 Pro Lys Pro Val Tyr Ala Gln Val Gly Gln Pro Asp Val Asp Leu Pro 385 390 395 400 Val Ser Pro Ser Asp Gly Val Leu Pro Asn Ser Thr His Glu Asp Gly 405 410 415 Ile Leu Arg Pro Ser Met Lys Leu Val Lys Phe Arg Lys Gly Asp Ser 420 425 430 Val Gly Leu Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val Ala 435 440 445 Gly Val Leu Glu Asp Ser Pro Ala Ala Lys Glu Gly Leu Glu Glu Gly 450 455 460 Asp Gln Ile Leu Arg Val Asn Asn Val Asp Phe Thr Asn Ile Ile Arg 465 470 475 480 Glu Glu Ala Val Leu Phe Leu Leu Asp Leu Pro Lys Gly Glu Glu Val 485 490 495 Thr Ile Leu Ala Gln Lys Lys Lys Asp Val Tyr Arg Arg Ile Val Glu 500 505 510 Ser Asp Val Gly Asp Ser Phe Tyr Ile Arg Thr His Phe Glu Tyr Glu 515 520 525 Lys Glu Ser Pro Tyr Gly Leu Ser Phe Asn Lys Gly Glu Val Phe Arg 530 535 540 Val Val Asp Thr Leu Tyr Asn Gly Lys Leu Gly Ser Trp Leu Ala Ile 545 550 555 560 Arg Ile Gly Lys Asn His Lys Glu Val Glu Arg Gly Ile Ile Pro Asn 565 570 575 Lys Asn Arg Ala Glu Gln Leu Ala Ser Val Gln Tyr Thr Leu Pro Lys 580 585 590 Thr Ala Gly Gly Asp Arg Ala Asp Phe Trp Arg Phe Arg Gly Leu Arg 595 600 605 Ser Ser Lys Arg Asn Leu Arg Lys Ser Arg Glu Asp Leu Ser Ala Gln 610 615 620 Pro Val Gln Thr Lys Phe Pro Ala Tyr Glu Arg Val Val Leu Arg Glu 625 630 635 640 Ala Gly Phe Leu Arg Pro Val Thr Ile Phe Gly Pro Ile Ala Asp Val 645 650 655 Ala Arg Glu Lys Leu Ala Arg Glu Glu Pro Asp Ile Tyr Gln Ile Ala 660 665 670 Lys Ser Glu Pro Arg Asp Ala Gly Thr Asp Gln Arg Ser Ser Gly Ile 675 680 685 Ile Arg Leu His Thr Ile Lys Gln Ile Ile Asp Gln Asp Lys His Ala 690 695 700 Leu Leu Asp Val Thr Pro Asn Ala Val Asp Arg Leu Asn Tyr Ala Gln 705 710 715 720 Trp Tyr Pro Ile Val Val Phe Leu Asn Pro Asp Ser Lys Gln Gly Val 725 730 735 Lys Thr Met Arg Met Arg Leu Cys Pro Glu Ser Arg Lys Ser Ala Arg 740 745 750 Lys Leu Tyr Glu Arg Ser His Lys Leu Arg Lys Asn Asn His His Leu 755 760 765 Phe Thr Thr Thr Ile Asn Leu Asn Ser Met Asn Asp Gly Trp Tyr Gly 770 775 780 Ala Leu Lys Glu Ala Ile Gln Gln Gln Gln Asn Gln Leu Val Trp Val 785 790 795 800 Ser Glu Gly Lys Ala Asp Gly Ala Thr Ser Asp Asp Leu Asp Leu His 805 810 815 Asp Asp Arg Leu Ser Tyr Leu Ser Ala Pro Gly Ser Glu Tyr Ser Met 820 825 830 Tyr Ser Thr Asp Ser Arg His Thr Ser Asp Tyr Glu Asp Thr Asp Thr 835 840 845 Glu Gly Gly Ala Tyr Thr Asp Gln Glu Leu Asp Glu Thr Leu Asn Asp 850 855 860 Glu Val Gly Thr Pro Pro Glu Ser Ala Ile Thr Arg Ser Ser Glu Pro 865 870 875 880 Val Arg Glu Asp Ser Ser Gly Met His His Glu Asn Gln Thr Tyr Pro 885 890 895 Pro Tyr Ser Pro Gln Ala Gln Pro Gln Pro Ile His Arg Ile Asp Ser 900 905 910 Pro Gly Phe Lys Pro Ala Ser Gln Gln Val Tyr Arg Lys Asp Pro Tyr 915 920 925 Pro Glu Glu Met Met Arg Gln Asn His Val Leu Lys Gln Pro Ala Val 930 935 940 Ser His Pro Gly His Arg Pro Asp Lys Glu Pro Asn Leu Thr Tyr Glu 945 950 955 960 Pro Gln Leu Pro Tyr Val Glu Lys Gln Ala Ser Arg Asp Leu Glu Gln 965 970 975 Pro Thr Tyr Arg Tyr Glu Ser Ser Ser Tyr Thr Asp Gln Phe Ser Arg 980 985 990 Asn Tyr Glu His Arg Leu Arg Tyr Glu Asp Arg Val Pro Met Tyr Glu 995 1000 1005 Glu Gln Trp Ser Tyr Tyr Asp Asp Lys Gln Pro Tyr Pro Ser Arg 1010 1015 1020 Pro Pro Phe Asp Asn Gln His Ser Gln Asp Leu Asp Ser Arg Gln 1025 1030 1035 His Pro Glu Glu Ser Ser Glu Arg Gly Tyr Phe Pro Arg Phe Glu 1040 1045 1050 Glu Pro Ala Pro Leu Ser Tyr Asp Ser Arg Pro Arg Tyr Glu Gln 1055 1060 1065 Ala Pro Arg Ala Ser Ala Leu Arg His Glu Glu Gln Pro Ala Pro 1070 1075 1080 Gly Tyr Asp Thr His Gly Arg Leu Arg Pro Glu Ala Gln Pro His 1085 1090 1095 Pro Ser Ala Gly Pro Lys Pro Ala Glu Ser Lys Gln Tyr Phe Glu 1100 1105 1110 Gln Tyr Ser Arg Ser Tyr Glu Gln Val Pro Pro Gln Gly Phe Thr 1115 1120 1125 Ser Arg Ala Gly His Phe Glu Pro Leu His Gly Ala Ala Ala Val 1130 1135 1140 Pro Pro Leu Ile Pro Ser Ser Gln His Lys Pro Glu Ala Leu Pro 1145 1150 1155 Ser Asn Thr Lys Pro Leu Pro Pro Pro Pro Thr Gln Thr Glu Glu 1160 1165 1170 Glu Glu Asp Pro Ala Met Lys Pro Gln Ser Val Leu Thr Arg Val 1175 1180 1185 Lys Met Phe Glu Asn Lys Arg Ser Ala Ser Leu Glu Thr Lys Lys 1190 1195 1200 Asp Val Asn Asp Thr Gly Ser Phe Lys Pro Pro Glu Val Ala Ser 1205 1210 1215 Lys Pro Ser Gly Ala Pro Ile Ile Gly Pro Lys Pro Thr Ser Gln 1220 1225 1230 Asn Gln Phe Ser Glu His Asp Lys Thr Leu Tyr Arg Ile Pro Glu 1235 1240 1245 Pro Gln Lys Pro Gln Leu Lys Pro Pro Glu Asp Ile Val Arg Ser 1250 1255 1260 Asn His Tyr Asp Pro Glu Glu Asp Glu Glu Tyr Tyr Arg Lys Gln 1265 1270 1275 Leu Ser Tyr Phe Asp Arg Arg Ser Phe Glu Asn Lys Pro Pro Ala 1280 1285 1290 His Ile Ala Ala Ser His Leu Ser Glu Pro Ala Lys Pro Ala His 1295 1300 1305 Ser Gln Asn Gln Ser Asn Phe Ser Ser Tyr Ser Ser Lys Gly Lys 1310 1315 1320 Pro Pro Glu Ala Asp Gly Val Asp Arg Ser Phe Gly Glu Lys Arg 1325 1330 1335 Tyr Glu Pro Ile Gln Ala Thr Pro Pro Pro Pro Pro Leu Pro Ser 1340 1345 1350 Gln Tyr Ala Gln Pro Ser Gln Pro Val Thr Ser Ala Ser Leu His 1355 1360 1365 Ile His Ser Lys Gly Ala His Gly Glu Gly Asn Ser Val Ser Leu 1370 1375 1380 Asp Phe Gln Asn Ser Leu Val Ser Lys Pro Asp Pro Pro Pro Ser 1385 1390 1395 Gln Asn Lys Pro Ala Thr Phe Arg Pro Pro Asn Arg Glu Asp Thr 1400 1405 1410 Ala Gln Ala Ala Phe Tyr Pro Gln Lys Ser Phe Pro Asp Lys Ala 1415 1420 1425 Pro Val Asn Gly Thr Glu Gln Thr Gln Lys Thr Val Thr Pro Ala 1430 1435 1440 Tyr Asn Arg Phe Thr Pro Lys Pro Tyr Thr Ser Ser Ala Arg Pro 1445 1450 1455 Phe Glu Arg Lys Phe Glu Ser Pro Lys Phe Asn His Asn Leu Leu 1460 1465 1470 Pro Ser Glu Thr Ala His Lys Pro Asp Leu Ser Ser Lys Thr Pro 1475 1480 1485 Thr Ser Pro Lys Thr Leu Val Lys Ser His Ser Leu Ala Gln Pro 1490 1495 1500 Pro Glu Phe Asp Ser Gly Val Glu Thr Phe Ser Ile His Ala Glu 1505 1510 1515 Lys Pro Lys Tyr Gln Ile Asn Asn Ile Ser Thr Val Pro Lys Ala 1520 1525 1530 Ile Pro Val Ser Pro Ser Ala Val Glu Glu Asp Glu Asp Glu Asp 1535 1540 1545 Gly His Thr Val Val Ala Thr Ala Arg Gly Ile Phe Asn Ser Asn 1550 1555 1560 Gly Gly Val Leu Ser Ser Ile Glu Thr Gly Val Ser Ile Ile Ile 1565 1570 1575 Pro Gln Gly Ala Ile Pro Glu Gly Val Glu Gln Glu Ile Tyr Phe 1580 1585 1590 Lys Val Cys Arg Asp Asn Ser Ile Leu Pro Pro Leu Asp Lys Glu 1595 1600 1605 Lys Gly Glu Thr Leu Leu Ser Pro Leu Val Met Cys Gly Pro His 1610 1615 1620 Gly Leu Lys Phe Leu Lys Pro Val Glu Leu Arg Leu Pro His Cys 1625 1630 1635 Ala Ser Met Thr Pro Asp Gly Trp Ser Phe Ala Leu Lys Ser Ser 1640 1645 1650 Asp Ser Ser Ser Gly Asp Pro Lys Thr Trp Gln Asn Lys Cys Leu 1655 1660 1665 Pro Gly Asp Pro Asn Tyr Leu Val Gly Ala Asn Cys Val Ser Val 1670 1675 1680 Leu Ile Asp His Phe 1685 <![CDATA[<210> 161]]> <![CDATA[<211> 1748]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 161]]> Met Ser Ala Arg Ala Ala Ala Ala Lys Ser Thr Ala Met Glu Glu Thr 1 5 10 15 Ala Ile Trp Glu Gln His Thr Val Thr Leu His Arg Ala Pro Gly Phe 20 25 30 Gly Phe Gly Ile Ala Ile Ser Gly Gly Arg Asp Asn Pro His Phe Gln 35 40 45 Ser Gly Glu Thr Ser Ile Val Ile Ser Asp Val Leu Lys Gly Gly Pro 50 55 60 Ala Glu Gly Gln Leu Gln Glu Asn Asp Arg Val Ala Met Val Asn Gly 65 70 75 80 Val Ser Met Asp Asn Val Glu His Ala Phe Ala Val Gln Gln Leu Arg 85 90 95 Lys Ser Gly Lys Asn Ala Lys Ile Thr Ile Arg Arg Lys Lys Lys Val 100 105 110 Gln Ile Pro Val Ser Arg Pro Asp Pro Glu Pro Val Ser Asp Asn Glu 115 120 125 Glu Asp Ser Tyr Asp Glu Glu Ile His Asp Pro Arg Ser Gly Arg Ser 130 135 140 Gly Val Val Asn Arg Arg Ser Glu Lys Ile Trp Pro Arg Asp Arg Ser 145 150 155 160 Ala Ser Arg Glu Arg Ser Leu Ser Pro Arg Ser Asp Arg Arg Ser Val 165 170 175 Ala Ser Ser Gln Pro Ala Lys Pro Thr Lys Val Thr Leu Val Lys Ser 180 185 190 Arg Lys Asn Glu Glu Tyr Gly Leu Arg Leu Ala Ser His Ile Phe Val 195 200 205 Lys Glu Ile Ser Gln Asp Ser Leu Ala Ala Arg Asp Gly Asn Ile Gln 210 215 220 Glu Gly Asp Val Val Leu Lys Ile Asn Gly Thr Val Thr Glu Asn Met 225 230 235 240 Ser Leu Thr Asp Ala Lys Thr Leu Ile Glu Arg Ser Lys Gly Lys Leu 245 250 255 Lys Met Val Val Gln Arg Asp Glu Arg Ala Thr Leu Leu Asn Val Pro 260 265 270 Asp Leu Ser Asp Ser Ile His Ser Ala Asn Ala Ser Glu Arg Asp Asp 275 280 285 Ile Ser Glu Ile Gln Ser Leu Ala Ser Asp His Ser Gly Arg Ser His 290 295 300 Asp Arg Pro Pro Arg Arg Ser Arg Ser Arg Ser Pro Asp Gln Arg Ser 305 310 315 320 Glu Pro Ser Asp His Ser Arg His Ser Pro Gln Gln Pro Ser Asn Gly 325 330 335 Ser Leu Arg Ser Arg Asp Glu Glu Arg Ile Ser Lys Pro Gly Ala Val 340 345 350 Ser Thr Pro Val Lys His Ala Asp Asp His Thr Pro Lys Thr Val Glu 355 360 365 Glu Val Thr Val Glu Arg Asn Glu Lys Gln Thr Pro Ser Leu Pro Glu 370 375 380 Pro Lys Pro Val Tyr Ala Gln Val Gly Gln Pro Asp Val Asp Leu Pro 385 390 395 400 Val Ser Pro Ser Asp Gly Val Leu Pro Asn Ser Thr His Glu Asp Gly 405 410 415 Ile Leu Arg Pro Ser Met Lys Leu Val Lys Phe Arg Lys Gly Asp Ser 420 425 430 Val Gly Leu Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val Ala 435 440 445 Gly Val Leu Glu Asp Ser Pro Ala Ala Lys Glu Gly Leu Glu Glu Gly 450 455 460 Asp Gln Ile Leu Arg Val Asn Asn Val Asp Phe Thr Asn Ile Ile Arg 465 470 475 480 Glu Glu Ala Val Leu Phe Leu Leu Asp Leu Pro Lys Gly Glu Glu Val 485 490 495 Thr Ile Leu Ala Gln Lys Lys Lys Asp Val Tyr Arg Arg Ile Val Glu 500 505 510 Ser Asp Val Gly Asp Ser Phe Tyr Ile Arg Thr His Phe Glu Tyr Glu 515 520 525 Lys Glu Ser Pro Tyr Gly Leu Ser Phe Asn Lys Gly Glu Val Phe Arg 530 535 540 Val Val Asp Thr Leu Tyr Asn Gly Lys Leu Gly Ser Trp Leu Ala Ile 545 550 555 560 Arg Ile Gly Lys Asn His Lys Glu Val Glu Arg Gly Ile Ile Pro Asn 565 570 575 Lys Asn Arg Ala Glu Gln Leu Ala Ser Val Gln Tyr Thr Leu Pro Lys 580 585 590 Thr Ala Gly Gly Asp Arg Ala Asp Phe Trp Arg Phe Arg Gly Leu Arg 595 600 605 Ser Ser Lys Arg Asn Leu Arg Lys Ser Arg Glu Asp Leu Ser Ala Gln 610 615 620 Pro Val Gln Thr Lys Phe Pro Ala Tyr Glu Arg Val Val Leu Arg Glu 625 630 635 640 Ala Gly Phe Leu Arg Pro Val Thr Ile Phe Gly Pro Ile Ala Asp Val 645 650 655 Ala Arg Glu Lys Leu Ala Arg Glu Glu Pro Asp Ile Tyr Gln Ile Ala 660 665 670 Lys Ser Glu Pro Arg Asp Ala Gly Thr Asp Gln Arg Ser Ser Gly Ile 675 680 685 Ile Arg Leu His Thr Ile Lys Gln Ile Ile Asp Gln Asp Lys His Ala 690 695 700 Leu Leu Asp Val Thr Pro Asn Ala Val Asp Arg Leu Asn Tyr Ala Gln 705 710 715 720 Trp Tyr Pro Ile Val Val Phe Leu Asn Pro Asp Ser Lys Gln Gly Val 725 730 735 Lys Thr Met Arg Met Arg Leu Cys Pro Glu Ser Arg Lys Ser Ala Arg 740 745 750 Lys Leu Tyr Glu Arg Ser His Lys Leu Arg Lys Asn Asn His His Leu 755 760 765 Phe Thr Thr Thr Ile Asn Leu Asn Ser Met Asn Asp Gly Trp Tyr Gly 770 775 780 Ala Leu Lys Glu Ala Ile Gln Gln Gln Gln Asn Gln Leu Val Trp Val 785 790 795 800 Ser Glu Gly Lys Ala Asp Gly Ala Thr Ser Asp Asp Leu Asp Leu His 805 810 815 Asp Asp Arg Leu Ser Tyr Leu Ser Ala Pro Gly Ser Glu Tyr Ser Met 820 825 830 Tyr Ser Thr Asp Ser Arg His Thr Ser Asp Tyr Glu Asp Thr Asp Thr 835 840 845 Glu Gly Gly Ala Tyr Thr Asp Gln Glu Leu Asp Glu Thr Leu Asn Asp 850 855 860 Glu Val Gly Thr Pro Pro Glu Ser Ala Ile Thr Arg Ser Ser Glu Pro 865 870 875 880 Val Arg Glu Asp Ser Ser Gly Met His His Glu Asn Gln Thr Tyr Pro 885 890 895 Pro Tyr Ser Pro Gln Ala Gln Pro Gln Pro Ile His Arg Ile Asp Ser 900 905 910 Pro Gly Phe Lys Pro Ala Ser Gln Gln Lys Ala Glu Ala Ser Ser Pro 915 920 925 Val Pro Tyr Leu Ser Pro Glu Thr Asn Pro Ala Ser Ser Thr Ser Ala 930 935 940 Val Asn His Asn Val Asn Leu Thr Asn Val Arg Leu Glu Glu Pro Thr 945 950 955 960 Pro Ala Pro Ser Thr Ser Tyr Ser Pro Gln Ala Asp Ser Leu Arg Thr 965 970 975 Pro Ser Thr Glu Ala Ala His Ile Met Leu Arg Asp Gln Glu Pro Ser 980 985 990 Leu Ser Ser His Val Asp Pro Thr Lys Val Tyr Arg Lys Asp Pro Tyr 995 1000 1005 Pro Glu Glu Met Met Arg Gln Asn His Val Leu Lys Gln Pro Ala 1010 1015 1020 Val Ser His Pro Gly His Arg Pro Asp Lys Glu Pro Asn Leu Thr 1025 1030 1035 Tyr Glu Pro Gln Leu Pro Tyr Val Glu Lys Gln Ala Ser Arg Asp 1040 1045 1050 Leu Glu Gln Pro Thr Tyr Arg Tyr Glu Ser Ser Ser Tyr Thr Asp 1055 1060 1065 Gln Phe Ser Arg Asn Tyr Glu His Arg Leu Arg Tyr Glu Asp Arg 1070 1075 1080 Val Pro Met Tyr Glu Glu Gln Trp Ser Tyr Tyr Asp Asp Lys Gln 1085 1090 1095 Pro Tyr Pro Ser Arg Pro Pro Phe Asp Asn Gln His Ser Gln Asp 1100 1105 1110 Leu Asp Ser Arg Gln His Pro Glu Glu Ser Ser Glu Arg Gly Tyr 1115 1120 1125 Phe Pro Arg Phe Glu Glu Pro Ala Pro Leu Ser Tyr Asp Ser Arg 1130 1135 1140 Pro Arg Tyr Glu Gln Ala Pro Arg Ala Ser Ala Leu Arg His Glu 1145 1150 1155 Glu Gln Pro Ala Pro Gly Tyr Asp Thr His Gly Arg Leu Arg Pro 1160 1165 1170 Glu Ala Gln Pro His Pro Ser Ala Gly Pro Lys Pro Ala Glu Ser 1175 1180 1185 Lys Gln Tyr Phe Glu Gln Tyr Ser Arg Ser Tyr Glu Gln Val Pro 1190 1195 1200 Pro Gln Gly Phe Thr Ser Arg Ala Gly His Phe Glu Pro Leu His 1205 1210 1215 Gly Ala Ala Ala Val Pro Pro Leu Ile Pro Ser Ser Gln His Lys 1220 1225 1230 Pro Glu Ala Leu Pro Ser Asn Thr Lys Pro Leu Pro Pro Pro Pro 1235 1240 1245 Thr Gln Thr Glu Glu Glu Glu Asp Pro Ala Met Lys Pro Gln Ser 1250 1255 1260 Val Leu Thr Arg Val Lys Met Phe Glu Asn Lys Arg Ser Ala Ser 1265 1270 1275 Leu Glu Thr Lys Lys Asp Val Asn Asp Thr Gly Ser Phe Lys Pro 1280 1285 1290 Pro Glu Val Ala Ser Lys Pro Ser Gly Ala Pro Ile Ile Gly Pro 1295 1300 1305 Lys Pro Thr Ser Gln Asn Gln Phe Ser Glu His Asp Lys Thr Leu 1310 1315 1320 Tyr Arg Ile Pro Glu Pro Gln Lys Pro Gln Leu Lys Pro Pro Glu 1325 1330 1335 Asp Ile Val Arg Ser Asn His Tyr Asp Pro Glu Glu Asp Glu Glu 1340 1345 1350 Tyr Tyr Arg Lys Gln Leu Ser Tyr Phe Asp Arg Arg Ser Phe Glu 1355 1360 1365 Asn Lys Pro Pro Ala His Ile Ala Ala Ser His Leu Ser Glu Pro 1370 1375 1380 Ala Lys Pro Ala His Ser Gln Asn Gln Ser Asn Phe Ser Ser Tyr 1385 1390 1395 Ser Ser Lys Gly Lys Pro Pro Glu Ala Asp Gly Val Asp Arg Ser 1400 1405 1410 Phe Gly Glu Lys Arg Tyr Glu Pro Ile Gln Ala Thr Pro Pro Pro 1415 1420 1425 Pro Pro Leu Pro Ser Gln Tyr Ala Gln Pro Ser Gln Pro Val Thr 1430 1435 1440 Ser Ala Ser Leu His Ile His Ser Lys Gly Ala His Gly Glu Gly 1445 1450 1455 Asn Ser Val Ser Leu Asp Phe Gln Asn Ser Leu Val Ser Lys Pro 1460 1465 1470 Asp Pro Pro Pro Ser Gln Asn Lys Pro Ala Thr Phe Arg Pro Pro 1475 1480 1485 Asn Arg Glu Asp Thr Ala Gln Ala Ala Phe Tyr Pro Gln Lys Ser 1490 1495 1500 Phe Pro Asp Lys Ala Pro Val Asn Gly Thr Glu Gln Thr Gln Lys 1505 1510 1515 Thr Val Thr Pro Ala Tyr Asn Arg Phe Thr Pro Lys Pro Tyr Thr 1520 1525 1530 Ser Ser Ala Arg Pro Phe Glu Arg Lys Phe Glu Ser Pro Lys Phe 1535 1540 1545 Asn His Asn Leu Leu Pro Ser Glu Thr Ala His Lys Pro Asp Leu 1550 1555 1560 Ser Ser Lys Thr Pro Thr Ser Pro Lys Thr Leu Val Lys Ser His 1565 1570 1575 Ser Leu Ala Gln Pro Pro Glu Phe Asp Ser Gly Val Glu Thr Phe 1580 1585 1590 Ser Ile His Ala Glu Lys Pro Lys Tyr Gln Ile Asn Asn Ile Ser 1595 1600 1605 Thr Val Pro Lys Ala Ile Pro Val Ser Pro Ser Ala Val Glu Glu 1610 1615 1620 Asp Glu Asp Glu Asp Gly His Thr Val Val Ala Thr Ala Arg Gly 1625 1630 1635 Ile Phe Asn Ser Asn Gly Gly Val Leu Ser Ser Ile Glu Thr Gly 1640 1645 1650 Val Ser Ile Ile Ile Pro Gln Gly Ala Ile Pro Glu Gly Val Glu 1655 1660 1665 Gln Glu Ile Tyr Phe Lys Val Cys Arg Asp Asn Ser Ile Leu Pro 1670 1675 1680 Pro Leu Asp Lys Glu Lys Gly Glu Thr Leu Leu Ser Pro Leu Val 1685 1690 1695 Met Cys Gly Pro His Gly Leu Lys Phe Leu Lys Pro Val Glu Leu 1700 1705 1710 Arg Leu Pro His Cys Asp Pro Lys Thr Trp Gln Asn Lys Cys Leu 1715 1720 1725 Pro Gly Asp Pro Asn Tyr Leu Val Gly Ala Asn Cys Val Ser Val 1730 1735 1740 Leu Ile Asp His Phe 1745 <![CDATA[<210> 162]]> <![CDATA[<211> 1668]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 162]]> Met Ser Ala Arg Ala Ala Ala Ala Lys Ser Thr Ala Met Glu Glu Thr 1 5 10 15 Ala Ile Trp Glu Gln His Thr Val Thr Leu His Arg Ala Pro Gly Phe 20 25 30 Gly Phe Gly Ile Ala Ile Ser Gly Gly Arg Asp Asn Pro His Phe Gln 35 40 45 Ser Gly Glu Thr Ser Ile Val Ile Ser Asp Val Leu Lys Gly Gly Pro 50 55 60 Ala Glu Gly Gln Leu Gln Glu Asn Asp Arg Val Ala Met Val Asn Gly 65 70 75 80 Val Ser Met Asp Asn Val Glu His Ala Phe Ala Val Gln Gln Leu Arg 85 90 95 Lys Ser Gly Lys Asn Ala Lys Ile Thr Ile Arg Arg Lys Lys Lys Val 100 105 110 Gln Ile Pro Val Ser Arg Pro Asp Pro Glu Pro Val Ser Asp Asn Glu 115 120 125 Glu Asp Ser Tyr Asp Glu Glu Ile His Asp Pro Arg Ser Gly Arg Ser 130 135 140 Gly Val Val Asn Arg Arg Ser Glu Lys Ile Trp Pro Arg Asp Arg Ser 145 150 155 160 Ala Ser Arg Glu Arg Ser Leu Ser Pro Arg Ser Asp Arg Arg Ser Val 165 170 175 Ala Ser Ser Gln Pro Ala Lys Pro Thr Lys Val Thr Leu Val Lys Ser 180 185 190 Arg Lys Asn Glu Glu Tyr Gly Leu Arg Leu Ala Ser His Ile Phe Val 195 200 205 Lys Glu Ile Ser Gln Asp Ser Leu Ala Ala Arg Asp Gly Asn Ile Gln 210 215 220 Glu Gly Asp Val Val Leu Lys Ile Asn Gly Thr Val Thr Glu Asn Met 225 230 235 240 Ser Leu Thr Asp Ala Lys Thr Leu Ile Glu Arg Ser Lys Gly Lys Leu 245 250 255 Lys Met Val Val Gln Arg Asp Glu Arg Ala Thr Leu Leu Asn Val Pro 260 265 270 Asp Leu Ser Asp Ser Ile His Ser Ala Asn Ala Ser Glu Arg Asp Asp 275 280 285 Ile Ser Glu Ile Gln Ser Leu Ala Ser Asp His Ser Gly Arg Ser His 290 295 300 Asp Arg Pro Pro Arg Arg Ser Arg Ser Arg Ser Pro Asp Gln Arg Ser 305 310 315 320 Glu Pro Ser Asp His Ser Arg His Ser Pro Gln Gln Pro Ser Asn Gly 325 330 335 Ser Leu Arg Ser Arg Asp Glu Glu Arg Ile Ser Lys Pro Gly Ala Val 340 345 350 Ser Thr Pro Val Lys His Ala Asp Asp His Thr Pro Lys Thr Val Glu 355 360 365 Glu Val Thr Val Glu Arg Asn Glu Lys Gln Thr Pro Ser Leu Pro Glu 370 375 380 Pro Lys Pro Val Tyr Ala Gln Val Gly Gln Pro Asp Val Asp Leu Pro 385 390 395 400 Val Ser Pro Ser Asp Gly Val Leu Pro Asn Ser Thr His Glu Asp Gly 405 410 415 Ile Leu Arg Pro Ser Met Lys Leu Val Lys Phe Arg Lys Gly Asp Ser 420 425 430 Val Gly Leu Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val Ala 435 440 445 Gly Val Leu Glu Asp Ser Pro Ala Ala Lys Glu Gly Leu Glu Glu Gly 450 455 460 Asp Gln Ile Leu Arg Val Asn Asn Val Asp Phe Thr Asn Ile Ile Arg 465 470 475 480 Glu Glu Ala Val Leu Phe Leu Leu Asp Leu Pro Lys Gly Glu Glu Val 485 490 495 Thr Ile Leu Ala Gln Lys Lys Lys Asp Val Tyr Arg Arg Ile Val Glu 500 505 510 Ser Asp Val Gly Asp Ser Phe Tyr Ile Arg Thr His Phe Glu Tyr Glu 515 520 525 Lys Glu Ser Pro Tyr Gly Leu Ser Phe Asn Lys Gly Glu Val Phe Arg 530 535 540 Val Val Asp Thr Leu Tyr Asn Gly Lys Leu Gly Ser Trp Leu Ala Ile 545 550 555 560 Arg Ile Gly Lys Asn His Lys Glu Val Glu Arg Gly Ile Ile Pro Asn 565 570 575 Lys Asn Arg Ala Glu Gln Leu Ala Ser Val Gln Tyr Thr Leu Pro Lys 580 585 590 Thr Ala Gly Gly Asp Arg Ala Asp Phe Trp Arg Phe Arg Gly Leu Arg 595 600 605 Ser Ser Lys Arg Asn Leu Arg Lys Ser Arg Glu Asp Leu Ser Ala Gln 610 615 620 Pro Val Gln Thr Lys Phe Pro Ala Tyr Glu Arg Val Val Leu Arg Glu 625 630 635 640 Ala Gly Phe Leu Arg Pro Val Thr Ile Phe Gly Pro Ile Ala Asp Val 645 650 655 Ala Arg Glu Lys Leu Ala Arg Glu Glu Pro Asp Ile Tyr Gln Ile Ala 660 665 670 Lys Ser Glu Pro Arg Asp Ala Gly Thr Asp Gln Arg Ser Ser Gly Ile 675 680 685 Ile Arg Leu His Thr Ile Lys Gln Ile Ile Asp Gln Asp Lys His Ala 690 695 700 Leu Leu Asp Val Thr Pro Asn Ala Val Asp Arg Leu Asn Tyr Ala Gln 705 710 715 720 Trp Tyr Pro Ile Val Val Phe Leu Asn Pro Asp Ser Lys Gln Gly Val 725 730 735 Lys Thr Met Arg Met Arg Leu Cys Pro Glu Ser Arg Lys Ser Ala Arg 740 745 750 Lys Leu Tyr Glu Arg Ser His Lys Leu Arg Lys Asn Asn His His Leu 755 760 765 Phe Thr Thr Thr Ile Asn Leu Asn Ser Met Asn Asp Gly Trp Tyr Gly 770 775 780 Ala Leu Lys Glu Ala Ile Gln Gln Gln Gln Asn Gln Leu Val Trp Val 785 790 795 800 Ser Glu Gly Lys Ala Asp Gly Ala Thr Ser Asp Asp Leu Asp Leu His 805 810 815 Asp Asp Arg Leu Ser Tyr Leu Ser Ala Pro Gly Ser Glu Tyr Ser Met 820 825 830 Tyr Ser Thr Asp Ser Arg His Thr Ser Asp Tyr Glu Asp Thr Asp Thr 835 840 845 Glu Gly Gly Ala Tyr Thr Asp Gln Glu Leu Asp Glu Thr Leu Asn Asp 850 855 860 Glu Val Gly Thr Pro Pro Glu Ser Ala Ile Thr Arg Ser Ser Glu Pro 865 870 875 880 Val Arg Glu Asp Ser Ser Gly Met His His Glu Asn Gln Thr Tyr Pro 885 890 895 Pro Tyr Ser Pro Gln Ala Gln Pro Gln Pro Ile His Arg Ile Asp Ser 900 905 910 Pro Gly Phe Lys Pro Ala Ser Gln Gln Val Tyr Arg Lys Asp Pro Tyr 915 920 925 Pro Glu Glu Met Met Arg Gln Asn His Val Leu Lys Gln Pro Ala Val 930 935 940 Ser His Pro Gly His Arg Pro Asp Lys Glu Pro Asn Leu Thr Tyr Glu 945 950 955 960 Pro Gln Leu Pro Tyr Val Glu Lys Gln Ala Ser Arg Asp Leu Glu Gln 965 970 975 Pro Thr Tyr Arg Tyr Glu Ser Ser Ser Tyr Thr Asp Gln Phe Ser Arg 980 985 990 Asn Tyr Glu His Arg Leu Arg Tyr Glu Asp Arg Val Pro Met Tyr Glu 995 1000 1005 Glu Gln Trp Ser Tyr Tyr Asp Asp Lys Gln Pro Tyr Pro Ser Arg 1010 1015 1020 Pro Pro Phe Asp Asn Gln His Ser Gln Asp Leu Asp Ser Arg Gln 1025 1030 1035 His Pro Glu Glu Ser Ser Glu Arg Gly Tyr Phe Pro Arg Phe Glu 1040 1045 1050 Glu Pro Ala Pro Leu Ser Tyr Asp Ser Arg Pro Arg Tyr Glu Gln 1055 1060 1065 Ala Pro Arg Ala Ser Ala Leu Arg His Glu Glu Gln Pro Ala Pro 1070 1075 1080 Gly Tyr Asp Thr His Gly Arg Leu Arg Pro Glu Ala Gln Pro His 1085 1090 1095 Pro Ser Ala Gly Pro Lys Pro Ala Glu Ser Lys Gln Tyr Phe Glu 1100 1105 1110 Gln Tyr Ser Arg Ser Tyr Glu Gln Val Pro Pro Gln Gly Phe Thr 1115 1120 1125 Ser Arg Ala Gly His Phe Glu Pro Leu His Gly Ala Ala Ala Val 1130 1135 1140 Pro Pro Leu Ile Pro Ser Ser Gln His Lys Pro Glu Ala Leu Pro 1145 1150 1155 Ser Asn Thr Lys Pro Leu Pro Pro Pro Pro Thr Gln Thr Glu Glu 1160 1165 1170 Glu Glu Asp Pro Ala Met Lys Pro Gln Ser Val Leu Thr Arg Val 1175 1180 1185 Lys Met Phe Glu Asn Lys Arg Ser Ala Ser Leu Glu Thr Lys Lys 1190 1195 1200 Asp Val Asn Asp Thr Gly Ser Phe Lys Pro Pro Glu Val Ala Ser 1205 1210 1215 Lys Pro Ser Gly Ala Pro Ile Ile Gly Pro Lys Pro Thr Ser Gln 1220 1225 1230 Asn Gln Phe Ser Glu His Asp Lys Thr Leu Tyr Arg Ile Pro Glu 1235 1240 1245 Pro Gln Lys Pro Gln Leu Lys Pro Pro Glu Asp Ile Val Arg Ser 1250 1255 1260 Asn His Tyr Asp Pro Glu Glu Asp Glu Glu Tyr Tyr Arg Lys Gln 1265 1270 1275 Leu Ser Tyr Phe Asp Arg Arg Ser Phe Glu Asn Lys Pro Pro Ala 1280 1285 1290 His Ile Ala Ala Ser His Leu Ser Glu Pro Ala Lys Pro Ala His 1295 1300 1305 Ser Gln Asn Gln Ser Asn Phe Ser Ser Tyr Ser Ser Lys Gly Lys 1310 1315 1320 Pro Pro Glu Ala Asp Gly Val Asp Arg Ser Phe Gly Glu Lys Arg 1325 1330 1335 Tyr Glu Pro Ile Gln Ala Thr Pro Pro Pro Pro Pro Leu Pro Ser 1340 1345 1350 Gln Tyr Ala Gln Pro Ser Gln Pro Val Thr Ser Ala Ser Leu His 1355 1360 1365 Ile His Ser Lys Gly Ala His Gly Glu Gly Asn Ser Val Ser Leu 1370 1375 1380 Asp Phe Gln Asn Ser Leu Val Ser Lys Pro Asp Pro Pro Pro Ser 1385 1390 1395 Gln Asn Lys Pro Ala Thr Phe Arg Pro Pro Asn Arg Glu Asp Thr 1400 1405 1410 Ala Gln Ala Ala Phe Tyr Pro Gln Lys Ser Phe Pro Asp Lys Ala 1415 1420 1425 Pro Val Asn Gly Thr Glu Gln Thr Gln Lys Thr Val Thr Pro Ala 1430 1435 1440 Tyr Asn Arg Phe Thr Pro Lys Pro Tyr Thr Ser Ser Ala Arg Pro 1445 1450 1455 Phe Glu Arg Lys Phe Glu Ser Pro Lys Phe Asn His Asn Leu Leu 1460 1465 1470 Pro Ser Glu Thr Ala His Lys Pro Asp Leu Ser Ser Lys Thr Pro 1475 1480 1485 Thr Ser Pro Lys Thr Leu Val Lys Ser His Ser Leu Ala Gln Pro 1490 1495 1500 Pro Glu Phe Asp Ser Gly Val Glu Thr Phe Ser Ile His Ala Glu 1505 1510 1515 Lys Pro Lys Tyr Gln Ile Asn Asn Ile Ser Thr Val Pro Lys Ala 1520 1525 1530 Ile Pro Val Ser Pro Ser Ala Val Glu Glu Asp Glu Asp Glu Asp 1535 1540 1545 Gly His Thr Val Val Ala Thr Ala Arg Gly Ile Phe Asn Ser Asn 1550 1555 1560 Gly Gly Val Leu Ser Ser Ile Glu Thr Gly Val Ser Ile Ile Ile 1565 1570 1575 Pro Gln Gly Ala Ile Pro Glu Gly Val Glu Gln Glu Ile Tyr Phe 1580 1585 1590 Lys Val Cys Arg Asp Asn Ser Ile Leu Pro Pro Leu Asp Lys Glu 1595 1600 1605 Lys Gly Glu Thr Leu Leu Ser Pro Leu Val Met Cys Gly Pro His 1610 1615 1620 Gly Leu Lys Phe Leu Lys Pro Val Glu Leu Arg Leu Pro His Cys 1625 1630 1635 Asp Pro Lys Thr Trp Gln Asn Lys Cys Leu Pro Gly Asp Pro Asn 1640 1645 1650 Tyr Leu Val Gly Ala Asn Cys Val Ser Val Leu Ile Asp His Phe 1655 1660 1665 <![CDATA[<210> 163]]> <![CDATA[<211> 848]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 163]]> Met Leu Gln Thr Lys Asp Leu Ile Trp Thr Leu Phe Phe Leu Gly Thr 1 5 10 15 Ala Val Ser Leu Gln Val Asp Ile Val Pro Ser Gln Gly Glu Ile Ser 20 25 30 Val Gly Glu Ser Lys Phe Phe Leu Cys Gln Val Ala Gly Asp Ala Lys 35 40 45 Asp Lys Asp Ile Ser Trp Phe Ser Pro Asn Gly Glu Lys Leu Thr Pro 50 55 60 Asn Gln Gln Arg Ile Ser Val Val Trp Asn Asp Asp Ser Ser Ser Thr 65 70 75 80 Leu Thr Ile Tyr Asn Ala Asn Ile Asp Asp Ala Gly Ile Tyr Lys Cys 85 90 95 Val Val Thr Gly Glu Asp Gly Ser Glu Ser Glu Ala Thr Val Asn Val 100 105 110 Lys Ile Phe Gln Lys Leu Met Phe Lys Asn Ala Pro Thr Pro Gln Glu 115 120 125 Phe Arg Glu Gly Glu Asp Ala Val Ile Val Cys Asp Val Val Ser Ser 130 135 140 Leu Pro Pro Thr Ile Ile Trp Lys His Lys Gly Arg Asp Val Ile Leu 145 150 155 160 Lys Lys Asp Val Arg Phe Ile Val Leu Ser Asn Asn Tyr Leu Gln Ile 165 170 175 Arg Gly Ile Lys Lys Thr Asp Glu Gly Thr Tyr Arg Cys Glu Gly Arg 180 185 190 Ile Leu Ala Arg Gly Glu Ile Asn Phe Lys Asp Ile Gln Val Ile Val 195 200 205 Asn Val Pro Pro Thr Ile Gln Ala Arg Gln Asn Ile Val Asn Ala Thr 210 215 220 Ala Asn Leu Gly Gln Ser Val Thr Leu Val Cys Asp Ala Glu Gly Phe 225 230 235 240 Pro Glu Pro Thr Met Ser Trp Thr Lys Asp Gly Glu Gln Ile Glu Gln 245 250 255 Glu Glu Asp Asp Glu Lys Tyr Ile Phe Ser Asp Asp Ser Ser Gln Leu 260 265 270 Thr Ile Lys Lys Val Asp Lys Asn Asp Glu Ala Glu Tyr Ile Cys Ile 275 280 285 Ala Glu Asn Lys Ala Gly Glu Gln Asp Ala Thr Ile His Leu Lys Val 290 295 300 Phe Ala Lys Pro Lys Ile Thr Tyr Val Glu Asn Gln Thr Ala Met Glu 305 310 315 320 Leu Glu Glu Gln Val Thr Leu Thr Cys Glu Ala Ser Gly Asp Pro Ile 325 330 335 Pro Ser Ile Thr Trp Arg Thr Ser Thr Arg Asn Ile Ser Ser Glu Glu 340 345 350 Lys Thr Leu Asp Gly His Met Val Val Arg Ser His Ala Arg Val Ser 355 360 365 Ser Leu Thr Leu Lys Ser Ile Gln Tyr Thr Asp Ala Gly Glu Tyr Ile 370 375 380 Cys Thr Ala Ser Asn Thr Ile Gly Gln Asp Ser Gln Ser Met Tyr Leu 385 390 395 400 Glu Val Gln Tyr Ala Pro Lys Leu Gln Gly Pro Val Ala Val Tyr Thr 405 410 415 Trp Glu Gly Asn Gln Val Asn Ile Thr Cys Glu Val Phe Ala Tyr Pro 420 425 430 Ser Ala Thr Ile Ser Trp Phe Arg Asp Gly Gln Leu Leu Pro Ser Ser 435 440 445 Asn Tyr Ser Asn Ile Lys Ile Tyr Asn Thr Pro Ser Ala Ser Tyr Leu 450 455 460 Glu Val Thr Pro Asp Ser Glu Asn Asp Phe Gly Asn Tyr Asn Cys Thr 465 470 475 480 Ala Val Asn Arg Ile Gly Gln Glu Ser Leu Glu Phe Ile Leu Val Gln 485 490 495 Ala Asp Thr Pro Ser Ser Pro Ser Ile Asp Gln Val Glu Pro Tyr Ser 500 505 510 Ser Thr Ala Gln Val Gln Phe Asp Glu Pro Glu Ala Thr Gly Gly Val 515 520 525 Pro Ile Leu Lys Tyr Lys Ala Glu Trp Arg Ala Val Gly Glu Glu Val 530 535 540 Trp His Ser Lys Trp Tyr Asp Ala Lys Glu Ala Ser Met Glu Gly Ile 545 550 555 560 Val Thr Ile Val Gly Leu Lys Pro Glu Thr Thr Tyr Ala Val Arg Leu 565 570 575 Ala Ala Leu Asn Gly Lys Gly Leu Gly Glu Ile Ser Ala Ala Ser Glu 580 585 590 Phe Lys Thr Gln Pro Val Gln Gly Glu Pro Ser Ala Pro Lys Leu Glu 595 600 605 Gly Gln Met Gly Glu Asp Gly Asn Ser Ile Lys Val Asn Leu Ile Lys 610 615 620 Gln Asp Asp Gly Gly Ser Pro Ile Arg His Tyr Leu Val Arg Tyr Arg 625 630 635 640 Ala Leu Ser Ser Glu Trp Lys Pro Glu Ile Arg Leu Pro Ser Gly Ser 645 650 655 Asp His Val Met Leu Lys Ser Leu Asp Trp Asn Ala Glu Tyr Glu Val 660 665 670 Tyr Val Val Ala Glu Asn Gln Gln Gly Lys Ser Lys Ala Ala His Phe 675 680 685 Val Phe Arg Thr Ser Ala Gln Pro Thr Ala Ile Pro Ala Asn Gly Ser 690 695 700 Pro Thr Ser Gly Leu Ser Thr Gly Ala Ile Val Gly Ile Leu Ile Val 705 710 715 720 Ile Phe Val Leu Leu Leu Val Val Val Asp Ile Thr Cys Tyr Phe Leu 725 730 735 Asn Lys Cys Gly Leu Phe Met Cys Ile Ala Val Asn Leu Cys Gly Lys 740 745 750 Ala Gly Pro Gly Ala Lys Gly Lys Asp Met Glu Glu Gly Lys Ala Ala 755 760 765 Phe Ser Lys Asp Glu Ser Lys Glu Pro Ile Val Glu Val Arg Thr Glu 770 775 780 Glu Glu Arg Thr Pro Asn His Asp Gly Gly Lys His Thr Glu Pro Asn 785 790 795 800 Glu Thr Thr Pro Leu Thr Glu Pro Glu Lys Gly Pro Val Glu Ala Lys 805 810 815 Pro Glu Cys Gln Glu Thr Glu Thr Lys Pro Ala Pro Ala Glu Val Lys 820 825 830 Thr Val Pro Asn Asp Ala Thr Gln Thr Lys Glu Asn Glu Ser Lys Ala 835 840 845 <![CDATA[<210> 164]]> <![CDATA[<211> 761]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 164]]> Met Leu Gln Thr Lys Asp Leu Ile Trp Thr Leu Phe Phe Leu Gly Thr 1 5 10 15 Ala Val Ser Leu Gln Val Asp Ile Val Pro Ser Gln Gly Glu Ile Ser 20 25 30 Val Gly Glu Ser Lys Phe Phe Leu Cys Gln Val Ala Gly Asp Ala Lys 35 40 45 Asp Lys Asp Ile Ser Trp Phe Ser Pro Asn Gly Glu Lys Leu Thr Pro 50 55 60 Asn Gln Gln Arg Ile Ser Val Val Trp Asn Asp Asp Ser Ser Ser Thr 65 70 75 80 Leu Thr Ile Tyr Asn Ala Asn Ile Asp Asp Ala Gly Ile Tyr Lys Cys 85 90 95 Val Val Thr Gly Glu Asp Gly Ser Glu Ser Glu Ala Thr Val Asn Val 100 105 110 Lys Ile Phe Gln Lys Leu Met Phe Lys Asn Ala Pro Thr Pro Gln Glu 115 120 125 Phe Arg Glu Gly Glu Asp Ala Val Ile Val Cys Asp Val Val Ser Ser 130 135 140 Leu Pro Pro Thr Ile Ile Trp Lys His Lys Gly Arg Asp Val Ile Leu 145 150 155 160 Lys Lys Asp Val Arg Phe Ile Val Leu Ser Asn Asn Tyr Leu Gln Ile 165 170 175 Arg Gly Ile Lys Lys Thr Asp Glu Gly Thr Tyr Arg Cys Glu Gly Arg 180 185 190 Ile Leu Ala Arg Gly Glu Ile Asn Phe Lys Asp Ile Gln Val Ile Val 195 200 205 Asn Val Pro Pro Thr Ile Gln Ala Arg Gln Asn Ile Val Asn Ala Thr 210 215 220 Ala Asn Leu Gly Gln Ser Val Thr Leu Val Cys Asp Ala Glu Gly Phe 225 230 235 240 Pro Glu Pro Thr Met Ser Trp Thr Lys Asp Gly Glu Gln Ile Glu Gln 245 250 255 Glu Glu Asp Asp Glu Lys Tyr Ile Phe Ser Asp Asp Ser Ser Gln Leu 260 265 270 Thr Ile Lys Lys Val Asp Lys Asn Asp Glu Ala Glu Tyr Ile Cys Ile 275 280 285 Ala Glu Asn Lys Ala Gly Glu Gln Asp Ala Thr Ile His Leu Lys Val 290 295 300 Phe Ala Lys Pro Lys Ile Thr Tyr Val Glu Asn Gln Thr Ala Met Glu 305 310 315 320 Leu Glu Glu Gln Val Thr Leu Thr Cys Glu Ala Ser Gly Asp Pro Ile 325 330 335 Pro Ser Ile Thr Trp Arg Thr Ser Thr Arg Asn Ile Ser Ser Glu Glu 340 345 350 Lys Thr Leu Asp Gly His Met Val Val Arg Ser His Ala Arg Val Ser 355 360 365 Ser Leu Thr Leu Lys Ser Ile Gln Tyr Thr Asp Ala Gly Glu Tyr Ile 370 375 380 Cys Thr Ala Ser Asn Thr Ile Gly Gln Asp Ser Gln Ser Met Tyr Leu 385 390 395 400 Glu Val Gln Tyr Ala Pro Lys Leu Gln Gly Pro Val Ala Val Tyr Thr 405 410 415 Trp Glu Gly Asn Gln Val Asn Ile Thr Cys Glu Val Phe Ala Tyr Pro 420 425 430 Ser Ala Thr Ile Ser Trp Phe Arg Asp Gly Gln Leu Leu Pro Ser Ser 435 440 445 Asn Tyr Ser Asn Ile Lys Ile Tyr Asn Thr Pro Ser Ala Ser Tyr Leu 450 455 460 Glu Val Thr Pro Asp Ser Glu Asn Asp Phe Gly Asn Tyr Asn Cys Thr 465 470 475 480 Ala Val Asn Arg Ile Gly Gln Glu Ser Leu Glu Phe Ile Leu Val Gln 485 490 495 Ala Asp Thr Pro Ser Ser Pro Ser Ile Asp Gln Val Glu Pro Tyr Ser 500 505 510 Ser Thr Ala Gln Val Gln Phe Asp Glu Pro Glu Ala Thr Gly Gly Val 515 520 525 Pro Ile Leu Lys Tyr Lys Ala Glu Trp Arg Ala Val Gly Glu Glu Val 530 535 540 Trp His Ser Lys Trp Tyr Asp Ala Lys Glu Ala Ser Met Glu Gly Ile 545 550 555 560 Val Thr Ile Val Gly Leu Lys Pro Glu Thr Thr Tyr Ala Val Arg Leu 565 570 575 Ala Ala Leu Asn Gly Lys Gly Leu Gly Glu Ile Ser Ala Ala Ser Glu 580 585 590 Phe Lys Thr Gln Pro Val His Ser Pro Pro Pro Pro Ala Ser Ala Ser 595 600 605 Ser Ser Thr Pro Val Pro Leu Ser Pro Pro Asp Thr Thr Trp Pro Leu 610 615 620 Pro Ala Leu Ala Thr Thr Glu Pro Ala Lys Gly Glu Pro Ser Ala Pro 625 630 635 640 Lys Leu Glu Gly Gln Met Gly Glu Asp Gly Asn Ser Ile Lys Val Asn 645 650 655 Leu Ile Lys Gln Asp Asp Gly Gly Ser Pro Ile Arg His Tyr Leu Val 660 665 670 Arg Tyr Arg Ala Leu Ser Ser Glu Trp Lys Pro Glu Ile Arg Leu Pro 675 680 685 Ser Gly Ser Asp His Val Met Leu Lys Ser Leu Asp Trp Asn Ala Glu 690 695 700 Tyr Glu Val Tyr Val Val Ala Glu Asn Gln Gln Gly Lys Ser Lys Ala 705 710 715 720 Ala His Phe Val Phe Arg Thr Ser Ala Gln Pro Thr Ala Ile Pro Ala 725 730 735 Thr Leu Gly Gly Asn Ser Ala Ser Tyr Thr Phe Val Ser Leu Leu Phe 740 745 750 Ser Ala Val Thr Leu Leu Leu Leu Cys 755 760 <![CDATA[<210> 165]]> <![CDATA[<211> 884]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 165]]> Met Leu Gln Thr Lys Asp Leu Ile Trp Thr Leu Phe Phe Leu Gly Thr 1 5 10 15 Ala Val Ser Leu Gln Val Asp Ile Val Pro Ser Gln Gly Glu Ile Ser 20 25 30 Val Gly Glu Ser Lys Phe Phe Leu Cys Gln Val Ala Gly Asp Ala Lys 35 40 45 Asp Lys Asp Ile Ser Trp Phe Ser Pro Asn Gly Glu Lys Leu Thr Pro 50 55 60 Asn Gln Gln Arg Ile Ser Val Val Trp Asn Asp Asp Ser Ser Ser Thr 65 70 75 80 Leu Thr Ile Tyr Asn Ala Asn Ile Asp Asp Ala Gly Ile Tyr Lys Cys 85 90 95 Val Val Thr Gly Glu Asp Gly Ser Glu Ser Glu Ala Thr Val Asn Val 100 105 110 Lys Ile Phe Gln Lys Leu Met Phe Lys Asn Ala Pro Thr Pro Gln Glu 115 120 125 Phe Arg Glu Gly Glu Asp Ala Val Ile Val Cys Asp Val Val Ser Ser 130 135 140 Leu Pro Pro Thr Ile Ile Trp Lys His Lys Gly Arg Asp Val Ile Leu 145 150 155 160 Lys Lys Asp Val Arg Phe Ile Val Leu Ser Asn Asn Tyr Leu Gln Ile 165 170 175 Arg Gly Ile Lys Lys Thr Asp Glu Gly Thr Tyr Arg Cys Glu Gly Arg 180 185 190 Ile Leu Ala Arg Gly Glu Ile Asn Phe Lys Asp Ile Gln Val Ile Val 195 200 205 Asn Val Pro Pro Thr Ile Gln Ala Arg Gln Asn Ile Val Asn Ala Thr 210 215 220 Ala Asn Leu Gly Gln Ser Val Thr Leu Val Cys Asp Ala Glu Gly Phe 225 230 235 240 Pro Glu Pro Thr Met Ser Trp Thr Lys Asp Gly Glu Gln Ile Glu Gln 245 250 255 Glu Glu Asp Asp Glu Lys Tyr Ile Phe Ser Asp Asp Ser Ser Gln Leu 260 265 270 Thr Ile Lys Lys Val Asp Lys Asn Asp Glu Ala Glu Tyr Ile Cys Ile 275 280 285 Ala Glu Asn Lys Ala Gly Glu Gln Asp Ala Thr Ile His Leu Lys Val 290 295 300 Phe Ala Lys Pro Lys Ile Thr Tyr Val Glu Asn Gln Thr Ala Met Glu 305 310 315 320 Leu Glu Glu Gln Val Thr Leu Thr Cys Glu Ala Ser Gly Asp Pro Ile 325 330 335 Pro Ser Ile Thr Trp Arg Thr Ser Thr Arg Asn Ile Ser Ser Glu Glu 340 345 350 Lys Ala Ser Trp Thr Arg Pro Glu Lys Gln Glu Val His Ala Pro Trp 355 360 365 Asn Trp Gln Val Gly Arg Gln Lys Gly Gln Ala Gly Ser Ala Gly Phe 370 375 380 Pro Gly Ser His Glu Thr Leu Asp Gly His Met Val Val Arg Ser His 385 390 395 400 Ala Arg Val Ser Ser Leu Thr Leu Lys Ser Ile Gln Tyr Thr Asp Ala 405 410 415 Gly Glu Tyr Ile Cys Thr Ala Ser Asn Thr Ile Gly Gln Asp Ser Gln 420 425 430 Ser Met Tyr Leu Glu Val Gln Tyr Ala Pro Lys Leu Gln Gly Pro Val 435 440 445 Ala Val Tyr Thr Trp Glu Gly Asn Gln Val Asn Ile Thr Cys Glu Val 450 455 460 Phe Ala Tyr Pro Ser Ala Thr Ile Ser Trp Phe Arg Asp Gly Gln Leu 465 470 475 480 Leu Pro Ser Ser Asn Tyr Ser Asn Ile Lys Ile Tyr Asn Thr Pro Ser 485 490 495 Ala Ser Tyr Leu Glu Val Thr Pro Asp Ser Glu Asn Asp Phe Gly Asn 500 505 510 Tyr Asn Cys Thr Ala Val Asn Arg Ile Gly Gln Glu Ser Leu Glu Phe 515 520 525 Ile Leu Val Gln Ala Asp Thr Pro Ser Ser Pro Ser Ile Asp Gln Val 530 535 540 Glu Pro Tyr Ser Ser Thr Ala Gln Val Gln Phe Asp Glu Pro Glu Ala 545 550 555 560 Thr Gly Gly Val Pro Ile Leu Lys Tyr Lys Ala Glu Trp Arg Ala Val 565 570 575 Gly Glu Glu Val Trp His Ser Lys Trp Tyr Asp Ala Lys Glu Ala Ser 580 585 590 Met Glu Gly Ile Val Thr Ile Val Gly Leu Lys Pro Glu Thr Thr Tyr 595 600 605 Ala Val Arg Leu Ala Ala Leu Asn Gly Lys Gly Leu Gly Glu Ile Ser 610 615 620 Ala Ala Ser Glu Phe Lys Thr Gln Pro Val Gln Gly Glu Pro Ser Ala 625 630 635 640 Pro Lys Leu Glu Gly Gln Met Gly Glu Asp Gly Asn Ser Ile Lys Val 645 650 655 Asn Leu Ile Lys Gln Asp Asp Gly Gly Ser Pro Ile Arg His Tyr Leu 660 665 670 Val Arg Tyr Arg Ala Leu Ser Ser Glu Trp Lys Pro Glu Ile Arg Leu 675 680 685 Pro Ser Gly Ser Asp His Val Met Leu Lys Ser Leu Asp Trp Asn Ala 690 695 700 Glu Tyr Glu Val Tyr Val Val Ala Glu Asn Gln Gln Gly Lys Ser Lys 705 710 715 720 Ala Ala His Phe Val Phe Arg Thr Ser Ala Gln Pro Thr Ala Ile Pro 725 730 735 Ala Asn Gly Ser Pro Thr Ser Gly Leu Ser Thr Gly Ala Ile Val Gly 740 745 750 Ile Leu Ile Val Ile Phe Val Leu Leu Leu Val Val Val Asp Ile Thr 755 760 765 Cys Tyr Phe Leu Asn Lys Cys Gly Leu Phe Met Cys Ile Ala Val Asn 770 775 780 Leu Cys Gly Lys Ala Gly Pro Gly Ala Lys Gly Lys Asp Met Glu Glu 785 790 795 800 Gly Lys Ala Ala Phe Ser Lys Asp Glu Ser Lys Glu Pro Ile Val Glu 805 810 815 Val Arg Thr Glu Glu Glu Arg Thr Pro Asn His Asp Gly Gly Lys His 820 825 830 Thr Glu Pro Asn Glu Thr Thr Pro Leu Thr Glu Pro Glu Lys Gly Pro 835 840 845 Val Glu Ala Lys Pro Glu Cys Gln Glu Thr Glu Thr Lys Pro Ala Pro 850 855 860 Ala Glu Val Lys Thr Val Pro Asn Asp Ala Thr Gln Thr Lys Glu Asn 865 870 875 880 Glu Ser Lys Ala <![CDATA[<210> 166]]> <![CDATA[<211> 726]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 166]]> Met Leu Gln Thr Lys Asp Leu Ile Trp Thr Leu Phe Phe Leu Gly Thr 1 5 10 15 Ala Val Ser Leu Gln Val Asp Ile Val Pro Ser Gln Gly Glu Ile Ser 20 25 30 Val Gly Glu Ser Lys Phe Phe Leu Cys Gln Val Ala Gly Asp Ala Lys 35 40 45 Asp Lys Asp Ile Ser Trp Phe Ser Pro Asn Gly Glu Lys Leu Thr Pro 50 55 60 Asn Gln Gln Arg Ile Ser Val Val Trp Asn Asp Asp Ser Ser Ser Thr 65 70 75 80 Leu Thr Ile Tyr Asn Ala Asn Ile Asp Asp Ala Gly Ile Tyr Lys Cys 85 90 95 Val Val Thr Gly Glu Asp Gly Ser Glu Ser Glu Ala Thr Val Asn Val 100 105 110 Lys Ile Phe Gln Lys Leu Met Phe Lys Asn Ala Pro Thr Pro Gln Glu 115 120 125 Phe Arg Glu Gly Glu Asp Ala Val Ile Val Cys Asp Val Val Ser Ser 130 135 140 Leu Pro Pro Thr Ile Ile Trp Lys His Lys Gly Arg Asp Val Ile Leu 145 150 155 160 Lys Lys Asp Val Arg Phe Ile Val Leu Ser Asn Asn Tyr Leu Gln Ile 165 170 175 Arg Gly Ile Lys Lys Thr Asp Glu Gly Thr Tyr Arg Cys Glu Gly Arg 180 185 190 Ile Leu Ala Arg Gly Glu Ile Asn Phe Lys Asp Ile Gln Val Ile Val 195 200 205 Asn Val Pro Pro Thr Ile Gln Ala Arg Gln Asn Ile Val Asn Ala Thr 210 215 220 Ala Asn Leu Gly Gln Ser Val Thr Leu Val Cys Asp Ala Glu Gly Phe 225 230 235 240 Pro Glu Pro Thr Met Ser Trp Thr Lys Asp Gly Glu Gln Ile Glu Gln 245 250 255 Glu Glu Asp Asp Glu Lys Tyr Ile Phe Ser Asp Asp Ser Ser Gln Leu 260 265 270 Thr Ile Lys Lys Val Asp Lys Asn Asp Glu Ala Glu Tyr Ile Cys Ile 275 280 285 Ala Glu Asn Lys Ala Gly Glu Gln Asp Ala Thr Ile His Leu Lys Val 290 295 300 Phe Ala Lys Pro Lys Ile Thr Tyr Val Glu Asn Gln Thr Ala Met Glu 305 310 315 320 Leu Glu Glu Gln Val Thr Leu Thr Cys Glu Ala Ser Gly Asp Pro Ile 325 330 335 Pro Ser Ile Thr Trp Arg Thr Ser Thr Arg Asn Ile Ser Ser Glu Glu 340 345 350 Lys Thr Leu Asp Gly His Met Val Val Arg Ser His Ala Arg Val Ser 355 360 365 Ser Leu Thr Leu Lys Ser Ile Gln Tyr Thr Asp Ala Gly Glu Tyr Ile 370 375 380 Cys Thr Ala Ser Asn Thr Ile Gly Gln Asp Ser Gln Ser Met Tyr Leu 385 390 395 400 Glu Val Gln Tyr Ala Pro Lys Leu Gln Gly Pro Val Ala Val Tyr Thr 405 410 415 Trp Glu Gly Asn Gln Val Asn Ile Thr Cys Glu Val Phe Ala Tyr Pro 420 425 430 Ser Ala Thr Ile Ser Trp Phe Arg Asp Gly Gln Leu Leu Pro Ser Ser 435 440 445 Asn Tyr Ser Asn Ile Lys Ile Tyr Asn Thr Pro Ser Ala Ser Tyr Leu 450 455 460 Glu Val Thr Pro Asp Ser Glu Asn Asp Phe Gly Asn Tyr Asn Cys Thr 465 470 475 480 Ala Val Asn Arg Ile Gly Gln Glu Ser Leu Glu Phe Ile Leu Val Gln 485 490 495 Ala Asp Thr Pro Ser Ser Pro Ser Ile Asp Gln Val Glu Pro Tyr Ser 500 505 510 Ser Thr Ala Gln Val Gln Phe Asp Glu Pro Glu Ala Thr Gly Gly Val 515 520 525 Pro Ile Leu Lys Tyr Lys Ala Glu Trp Arg Ala Val Gly Glu Glu Val 530 535 540 Trp His Ser Lys Trp Tyr Asp Ala Lys Glu Ala Ser Met Glu Gly Ile 545 550 555 560 Val Thr Ile Val Gly Leu Lys Pro Glu Thr Thr Tyr Ala Val Arg Leu 565 570 575 Ala Ala Leu Asn Gly Lys Gly Leu Gly Glu Ile Ser Ala Ala Ser Glu 580 585 590 Phe Lys Thr Gln Pro Val Gln Gly Glu Pro Ser Ala Pro Lys Leu Glu 595 600 605 Gly Gln Met Gly Glu Asp Gly Asn Ser Ile Lys Val Asn Leu Ile Lys 610 615 620 Gln Asp Asp Gly Gly Ser Pro Ile Arg His Tyr Leu Val Arg Tyr Arg 625 630 635 640 Ala Leu Ser Ser Glu Trp Lys Pro Glu Ile Arg Leu Pro Ser Gly Ser 645 650 655 Asp His Val Met Leu Lys Ser Leu Asp Trp Asn Ala Glu Tyr Glu Val 660 665 670 Tyr Val Val Ala Glu Asn Gln Gln Gly Lys Ser Lys Ala Ala His Phe 675 680 685 Val Phe Arg Thr Ser Ala Gln Pro Thr Ala Ile Pro Ala Thr Leu Gly 690 695 700 Gly Asn Ser Ala Ser Tyr Thr Phe Val Ser Leu Leu Phe Ser Ala Val 705 710 715 720 Thr Leu Leu Leu Leu Cys 725 <![CDATA[<210> 167]]> <![CDATA[<211> 735]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 167]]> Met Leu Gln Thr Lys Asp Leu Ile Trp Thr Leu Phe Phe Leu Gly Thr 1 5 10 15 Ala Val Ser Leu Gln Val Asp Ile Val Pro Ser Gln Gly Glu Ile Ser 20 25 30 Val Gly Glu Ser Lys Phe Phe Leu Cys Gln Val Ala Gly Asp Ala Lys 35 40 45 Asp Lys Asp Ile Ser Trp Phe Ser Pro Asn Gly Glu Lys Leu Thr Pro 50 55 60 Asn Gln Gln Arg Ile Ser Val Val Trp Asn Asp Asp Ser Ser Ser Thr 65 70 75 80 Leu Thr Ile Tyr Asn Ala Asn Ile Asp Asp Ala Gly Ile Tyr Lys Cys 85 90 95 Val Val Thr Gly Glu Asp Gly Ser Glu Ser Glu Ala Thr Val Asn Val 100 105 110 Lys Ile Phe Gln Lys Leu Met Phe Lys Asn Ala Pro Thr Pro Gln Glu 115 120 125 Phe Arg Glu Gly Glu Asp Ala Val Ile Val Cys Asp Val Val Ser Ser 130 135 140 Leu Pro Pro Thr Ile Ile Trp Lys His Lys Gly Arg Asp Val Ile Leu 145 150 155 160 Lys Lys Asp Val Arg Phe Ile Val Leu Ser Asn Asn Tyr Leu Gln Ile 165 170 175 Arg Gly Ile Lys Lys Thr Asp Glu Gly Thr Tyr Arg Cys Glu Gly Arg 180 185 190 Ile Leu Ala Arg Gly Glu Ile Asn Phe Lys Asp Ile Gln Val Ile Val 195 200 205 Asn Val Pro Pro Thr Ile Gln Ala Arg Gln Asn Ile Val Asn Ala Thr 210 215 220 Ala Asn Leu Gly Gln Ser Val Thr Leu Val Cys Asp Ala Glu Gly Phe 225 230 235 240 Pro Glu Pro Thr Met Ser Trp Thr Lys Asp Gly Glu Gln Ile Glu Gln 245 250 255 Glu Glu Asp Asp Glu Lys Tyr Ile Phe Ser Asp Asp Ser Ser Gln Leu 260 265 270 Thr Ile Lys Lys Val Asp Lys Asn Asp Glu Ala Glu Tyr Ile Cys Ile 275 280 285 Ala Glu Asn Lys Ala Gly Glu Gln Asp Ala Thr Ile His Leu Lys Val 290 295 300 Phe Ala Lys Pro Lys Ile Thr Tyr Val Glu Asn Gln Thr Ala Met Glu 305 310 315 320 Leu Glu Glu Gln Val Thr Leu Thr Cys Glu Ala Ser Gly Asp Pro Ile 325 330 335 Pro Ser Ile Thr Trp Arg Thr Ser Thr Arg Asn Ile Ser Ser Glu Glu 340 345 350 Lys Ala Ser Trp Thr Arg Pro Glu Lys Gln Glu Thr Leu Asp Gly His 355 360 365 Met Val Val Arg Ser His Ala Arg Val Ser Ser Leu Thr Leu Lys Ser 370 375 380 Ile Gln Tyr Thr Asp Ala Gly Glu Tyr Ile Cys Thr Ala Ser Asn Thr 385 390 395 400 Ile Gly Gln Asp Ser Gln Ser Met Tyr Leu Glu Val Gln Tyr Ala Pro 405 410 415 Lys Leu Gln Gly Pro Val Ala Val Tyr Thr Trp Glu Gly Asn Gln Val 420 425 430 Asn Ile Thr Cys Glu Val Phe Ala Tyr Pro Ser Ala Thr Ile Ser Trp 435 440 445 Phe Arg Asp Gly Gln Leu Leu Pro Ser Ser Asn Tyr Ser Asn Ile Lys 450 455 460 Ile Tyr Asn Thr Pro Ser Ala Ser Tyr Leu Glu Val Thr Pro Asp Ser 465 470 475 480 Glu Asn Asp Phe Gly Asn Tyr Asn Cys Thr Ala Val Asn Arg Ile Gly 485 490 495 Gln Glu Ser Leu Glu Phe Ile Leu Val Gln Ala Asp Thr Pro Ser Ser 500 505 510 Pro Ser Ile Asp Gln Val Glu Pro Tyr Ser Ser Thr Ala Gln Val Gln 515 520 525 Phe Asp Glu Pro Glu Ala Thr Gly Gly Val Pro Ile Leu Lys Tyr Lys 530 535 540 Ala Glu Trp Arg Ala Val Gly Glu Glu Val Trp His Ser Lys Trp Tyr 545 550 555 560 Asp Ala Lys Glu Ala Ser Met Glu Gly Ile Val Thr Ile Val Gly Leu 565 570 575 Lys Pro Glu Thr Thr Tyr Ala Val Arg Leu Ala Ala Leu Asn Gly Lys 580 585 590 Gly Leu Gly Glu Ile Ser Ala Ala Ser Glu Phe Lys Thr Gln Pro Val 595 600 605 Arg Glu Pro Ser Ala Pro Lys Leu Glu Gly Gln Met Gly Glu Asp Gly 610 615 620 Asn Ser Ile Lys Val Asn Leu Ile Lys Gln Asp Asp Gly Gly Ser Pro 625 630 635 640 Ile Arg His Tyr Leu Val Arg Tyr Arg Ala Leu Ser Ser Glu Trp Lys 645 650 655 Pro Glu Ile Arg Leu Pro Ser Gly Ser Asp His Val Met Leu Lys Ser 660 665 670 Leu Asp Trp Asn Ala Glu Tyr Glu Val Tyr Val Val Ala Glu Asn Gln 675 680 685 Gln Gly Lys Ser Lys Ala Ala His Phe Val Phe Arg Thr Ser Ala Gln 690 695 700 Pro Thr Ala Ile Pro Ala Thr Leu Gly Gly Asn Ser Ala Ser Tyr Thr 705 710 715 720 Phe Val Ser Leu Leu Phe Ser Ala Val Thr Leu Leu Leu Leu Cys 725 730 735 <![CDATA[<210> 168]]> <![CDATA[<211> 857]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 168]]> Met Leu Gln Thr Lys Asp Leu Ile Trp Thr Leu Phe Phe Leu Gly Thr 1 5 10 15 Ala Val Ser Leu Gln Val Asp Ile Val Pro Ser Gln Gly Glu Ile Ser 20 25 30 Val Gly Glu Ser Lys Phe Phe Leu Cys Gln Val Ala Gly Asp Ala Lys 35 40 45 Asp Lys Asp Ile Ser Trp Phe Ser Pro Asn Gly Glu Lys Leu Thr Pro 50 55 60 Asn Gln Gln Arg Ile Ser Val Val Trp Asn Asp Asp Ser Ser Ser Thr 65 70 75 80 Leu Thr Ile Tyr Asn Ala Asn Ile Asp Asp Ala Gly Ile Tyr Lys Cys 85 90 95 Val Val Thr Gly Glu Asp Gly Ser Glu Ser Glu Ala Thr Val Asn Val 100 105 110 Lys Ile Phe Gln Lys Leu Met Phe Lys Asn Ala Pro Thr Pro Gln Glu 115 120 125 Phe Arg Glu Gly Glu Asp Ala Val Ile Val Cys Asp Val Val Ser Ser 130 135 140 Leu Pro Pro Thr Ile Ile Trp Lys His Lys Gly Arg Asp Val Ile Leu 145 150 155 160 Lys Lys Asp Val Arg Phe Ile Val Leu Ser Asn Asn Tyr Leu Gln Ile 165 170 175 Arg Gly Ile Lys Lys Thr Asp Glu Gly Thr Tyr Arg Cys Glu Gly Arg 180 185 190 Ile Leu Ala Arg Gly Glu Ile Asn Phe Lys Asp Ile Gln Val Ile Val 195 200 205 Asn Val Pro Pro Thr Ile Gln Ala Arg Gln Asn Ile Val Asn Ala Thr 210 215 220 Ala Asn Leu Gly Gln Ser Val Thr Leu Val Cys Asp Ala Glu Gly Phe 225 230 235 240 Pro Glu Pro Thr Met Ser Trp Thr Lys Asp Gly Glu Gln Ile Glu Gln 245 250 255 Glu Glu Asp Asp Glu Lys Tyr Ile Phe Ser Asp Asp Ser Ser Gln Leu 260 265 270 Thr Ile Lys Lys Val Asp Lys Asn Asp Glu Ala Glu Tyr Ile Cys Ile 275 280 285 Ala Glu Asn Lys Ala Gly Glu Gln Asp Ala Thr Ile His Leu Lys Val 290 295 300 Phe Ala Lys Pro Lys Ile Thr Tyr Val Glu Asn Gln Thr Ala Met Glu 305 310 315 320 Leu Glu Glu Gln Val Thr Leu Thr Cys Glu Ala Ser Gly Asp Pro Ile 325 330 335 Pro Ser Ile Thr Trp Arg Thr Ser Thr Arg Asn Ile Ser Ser Glu Glu 340 345 350 Lys Ala Ser Trp Thr Arg Pro Glu Lys Gln Glu Thr Leu Asp Gly His 355 360 365 Met Val Val Arg Ser His Ala Arg Val Ser Ser Leu Thr Leu Lys Ser 370 375 380 Ile Gln Tyr Thr Asp Ala Gly Glu Tyr Ile Cys Thr Ala Ser Asn Thr 385 390 395 400 Ile Gly Gln Asp Ser Gln Ser Met Tyr Leu Glu Val Gln Tyr Ala Pro 405 410 415 Lys Leu Gln Gly Pro Val Ala Val Tyr Thr Trp Glu Gly Asn Gln Val 420 425 430 Asn Ile Thr Cys Glu Val Phe Ala Tyr Pro Ser Ala Thr Ile Ser Trp 435 440 445 Phe Arg Asp Gly Gln Leu Leu Pro Ser Ser Asn Tyr Ser Asn Ile Lys 450 455 460 Ile Tyr Asn Thr Pro Ser Ala Ser Tyr Leu Glu Val Thr Pro Asp Ser 465 470 475 480 Glu Asn Asp Phe Gly Asn Tyr Asn Cys Thr Ala Val Asn Arg Ile Gly 485 490 495 Gln Glu Ser Leu Glu Phe Ile Leu Val Gln Ala Asp Thr Pro Ser Ser 500 505 510 Pro Ser Ile Asp Gln Val Glu Pro Tyr Ser Ser Thr Ala Gln Val Gln 515 520 525 Phe Asp Glu Pro Glu Ala Thr Gly Gly Val Pro Ile Leu Lys Tyr Lys 530 535 540 Ala Glu Trp Arg Ala Val Gly Glu Glu Val Trp His Ser Lys Trp Tyr 545 550 555 560 Asp Ala Lys Glu Ala Ser Met Glu Gly Ile Val Thr Ile Val Gly Leu 565 570 575 Lys Pro Glu Thr Thr Tyr Ala Val Arg Leu Ala Ala Leu Asn Gly Lys 580 585 590 Gly Leu Gly Glu Ile Ser Ala Ala Ser Glu Phe Lys Thr Gln Pro Val 595 600 605 Arg Glu Pro Ser Ala Pro Lys Leu Glu Gly Gln Met Gly Glu Asp Gly 610 615 620 Asn Ser Ile Lys Val Asn Leu Ile Lys Gln Asp Asp Gly Gly Ser Pro 625 630 635 640 Ile Arg His Tyr Leu Val Arg Tyr Arg Ala Leu Ser Ser Glu Trp Lys 645 650 655 Pro Glu Ile Arg Leu Pro Ser Gly Ser Asp His Val Met Leu Lys Ser 660 665 670 Leu Asp Trp Asn Ala Glu Tyr Glu Val Tyr Val Val Ala Glu Asn Gln 675 680 685 Gln Gly Lys Ser Lys Ala Ala His Phe Val Phe Arg Thr Ser Ala Gln 690 695 700 Pro Thr Ala Ile Pro Ala Asn Gly Ser Pro Thr Ser Gly Leu Ser Thr 705 710 715 720 Gly Ala Ile Val Gly Ile Leu Ile Val Ile Phe Val Leu Leu Leu Val 725 730 735 Val Val Asp Ile Thr Cys Tyr Phe Leu Asn Lys Cys Gly Leu Phe Met 740 745 750 Cys Ile Ala Val Asn Leu Cys Gly Lys Ala Gly Pro Gly Ala Lys Gly 755 760 765 Lys Asp Met Glu Glu Gly Lys Ala Ala Phe Ser Lys Asp Glu Ser Lys 770 775 780 Glu Pro Ile Val Glu Val Arg Thr Glu Glu Glu Arg Thr Pro Asn His 785 790 795 800 Asp Gly Gly Lys His Thr Glu Pro Asn Glu Thr Thr Pro Leu Thr Glu 805 810 815 Pro Glu Lys Gly Pro Val Glu Ala Lys Pro Glu Cys Gln Glu Thr Glu 820 825 830 Thr Lys Pro Ala Pro Ala Glu Val Lys Thr Val Pro Asn Asp Ala Thr 835 840 845 Gln Thr Lys Glu Asn Glu Ser Lys Ala 850 855 <![CDATA[<210> 169]]> <![CDATA[<211> 725]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 169]]> Met Leu Gln Thr Lys Asp Leu Ile Trp Thr Leu Phe Phe Leu Gly Thr 1 5 10 15 Ala Val Ser Leu Gln Val Asp Ile Val Pro Ser Gln Gly Glu Ile Ser 20 25 30 Val Gly Glu Ser Lys Phe Phe Leu Cys Gln Val Ala Gly Asp Ala Lys 35 40 45 Asp Lys Asp Ile Ser Trp Phe Ser Pro Asn Gly Glu Lys Leu Thr Pro 50 55 60 Asn Gln Gln Arg Ile Ser Val Val Trp Asn Asp Asp Ser Ser Ser Thr 65 70 75 80 Leu Thr Ile Tyr Asn Ala Asn Ile Asp Asp Ala Gly Ile Tyr Lys Cys 85 90 95 Val Val Thr Gly Glu Asp Gly Ser Glu Ser Glu Ala Thr Val Asn Val 100 105 110 Lys Ile Phe Gln Lys Leu Met Phe Lys Asn Ala Pro Thr Pro Gln Glu 115 120 125 Phe Arg Glu Gly Glu Asp Ala Val Ile Val Cys Asp Val Val Ser Ser 130 135 140 Leu Pro Pro Thr Ile Ile Trp Lys His Lys Gly Arg Asp Val Ile Leu 145 150 155 160 Lys Lys Asp Val Arg Phe Ile Val Leu Ser Asn Asn Tyr Leu Gln Ile 165 170 175 Arg Gly Ile Lys Lys Thr Asp Glu Gly Thr Tyr Arg Cys Glu Gly Arg 180 185 190 Ile Leu Ala Arg Gly Glu Ile Asn Phe Lys Asp Ile Gln Val Ile Val 195 200 205 Asn Val Pro Pro Thr Ile Gln Ala Arg Gln Asn Ile Val Asn Ala Thr 210 215 220 Ala Asn Leu Gly Gln Ser Val Thr Leu Val Cys Asp Ala Glu Gly Phe 225 230 235 240 Pro Glu Pro Thr Met Ser Trp Thr Lys Asp Gly Glu Gln Ile Glu Gln 245 250 255 Glu Glu Asp Asp Glu Lys Tyr Ile Phe Ser Asp Asp Ser Ser Gln Leu 260 265 270 Thr Ile Lys Lys Val Asp Lys Asn Asp Glu Ala Glu Tyr Ile Cys Ile 275 280 285 Ala Glu Asn Lys Ala Gly Glu Gln Asp Ala Thr Ile His Leu Lys Val 290 295 300 Phe Ala Lys Pro Lys Ile Thr Tyr Val Glu Asn Gln Thr Ala Met Glu 305 310 315 320 Leu Glu Glu Gln Val Thr Leu Thr Cys Glu Ala Ser Gly Asp Pro Ile 325 330 335 Pro Ser Ile Thr Trp Arg Thr Ser Thr Arg Asn Ile Ser Ser Glu Glu 340 345 350 Lys Thr Leu Asp Gly His Met Val Val Arg Ser His Ala Arg Val Ser 355 360 365 Ser Leu Thr Leu Lys Ser Ile Gln Tyr Thr Asp Ala Gly Glu Tyr Ile 370 375 380 Cys Thr Ala Ser Asn Thr Ile Gly Gln Asp Ser Gln Ser Met Tyr Leu 385 390 395 400 Glu Val Gln Tyr Ala Pro Lys Leu Gln Gly Pro Val Ala Val Tyr Thr 405 410 415 Trp Glu Gly Asn Gln Val Asn Ile Thr Cys Glu Val Phe Ala Tyr Pro 420 425 430 Ser Ala Thr Ile Ser Trp Phe Arg Asp Gly Gln Leu Leu Pro Ser Ser 435 440 445 Asn Tyr Ser Asn Ile Lys Ile Tyr Asn Thr Pro Ser Ala Ser Tyr Leu 450 455 460 Glu Val Thr Pro Asp Ser Glu Asn Asp Phe Gly Asn Tyr Asn Cys Thr 465 470 475 480 Ala Val Asn Arg Ile Gly Gln Glu Ser Leu Glu Phe Ile Leu Val Gln 485 490 495 Ala Asp Thr Pro Ser Ser Pro Ser Ile Asp Gln Val Glu Pro Tyr Ser 500 505 510 Ser Thr Ala Gln Val Gln Phe Asp Glu Pro Glu Ala Thr Gly Gly Val 515 520 525 Pro Ile Leu Lys Tyr Lys Ala Glu Trp Arg Ala Val Gly Glu Glu Val 530 535 540 Trp His Ser Lys Trp Tyr Asp Ala Lys Glu Ala Ser Met Glu Gly Ile 545 550 555 560 Val Thr Ile Val Gly Leu Lys Pro Glu Thr Thr Tyr Ala Val Arg Leu 565 570 575 Ala Ala Leu Asn Gly Lys Gly Leu Gly Glu Ile Ser Ala Ala Ser Glu 580 585 590 Phe Lys Thr Gln Pro Val Arg Glu Pro Ser Ala Pro Lys Leu Glu Gly 595 600 605 Gln Met Gly Glu Asp Gly Asn Ser Ile Lys Val Asn Leu Ile Lys Gln 610 615 620 Asp Asp Gly Gly Ser Pro Ile Arg His Tyr Leu Val Arg Tyr Arg Ala 625 630 635 640 Leu Ser Ser Glu Trp Lys Pro Glu Ile Arg Leu Pro Ser Gly Ser Asp 645 650 655 His Val Met Leu Lys Ser Leu Asp Trp Asn Ala Glu Tyr Glu Val Tyr 660 665 670 Val Val Ala Glu Asn Gln Gln Gly Lys Ser Lys Ala Ala His Phe Val 675 680 685 Phe Arg Thr Ser Ala Gln Pro Thr Ala Ile Pro Ala Thr Leu Gly Gly 690 695 700 Asn Ser Ala Ser Tyr Thr Phe Val Ser Leu Leu Phe Ser Ala Val Thr 705 710 715 720 Leu Leu Leu Leu Cys 725 <![CDATA[<210> 170]]> <![CDATA[<211> 847]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 170]]> Met Leu Gln Thr Lys Asp Leu Ile Trp Thr Leu Phe Phe Leu Gly Thr 1 5 10 15 Ala Val Ser Leu Gln Val Asp Ile Val Pro Ser Gln Gly Glu Ile Ser 20 25 30 Val Gly Glu Ser Lys Phe Phe Leu Cys Gln Val Ala Gly Asp Ala Lys 35 40 45 Asp Lys Asp Ile Ser Trp Phe Ser Pro Asn Gly Glu Lys Leu Thr Pro 50 55 60 Asn Gln Gln Arg Ile Ser Val Val Trp Asn Asp Asp Ser Ser Ser Thr 65 70 75 80 Leu Thr Ile Tyr Asn Ala Asn Ile Asp Asp Ala Gly Ile Tyr Lys Cys 85 90 95 Val Val Thr Gly Glu Asp Gly Ser Glu Ser Glu Ala Thr Val Asn Val 100 105 110 Lys Ile Phe Gln Lys Leu Met Phe Lys Asn Ala Pro Thr Pro Gln Glu 115 120 125 Phe Arg Glu Gly Glu Asp Ala Val Ile Val Cys Asp Val Val Ser Ser 130 135 140 Leu Pro Pro Thr Ile Ile Trp Lys His Lys Gly Arg Asp Val Ile Leu 145 150 155 160 Lys Lys Asp Val Arg Phe Ile Val Leu Ser Asn Asn Tyr Leu Gln Ile 165 170 175 Arg Gly Ile Lys Lys Thr Asp Glu Gly Thr Tyr Arg Cys Glu Gly Arg 180 185 190 Ile Leu Ala Arg Gly Glu Ile Asn Phe Lys Asp Ile Gln Val Ile Val 195 200 205 Asn Val Pro Pro Thr Ile Gln Ala Arg Gln Asn Ile Val Asn Ala Thr 210 215 220 Ala Asn Leu Gly Gln Ser Val Thr Leu Val Cys Asp Ala Glu Gly Phe 225 230 235 240 Pro Glu Pro Thr Met Ser Trp Thr Lys Asp Gly Glu Gln Ile Glu Gln 245 250 255 Glu Glu Asp Asp Glu Lys Tyr Ile Phe Ser Asp Asp Ser Ser Gln Leu 260 265 270 Thr Ile Lys Lys Val Asp Lys Asn Asp Glu Ala Glu Tyr Ile Cys Ile 275 280 285 Ala Glu Asn Lys Ala Gly Glu Gln Asp Ala Thr Ile His Leu Lys Val 290 295 300 Phe Ala Lys Pro Lys Ile Thr Tyr Val Glu Asn Gln Thr Ala Met Glu 305 310 315 320 Leu Glu Glu Gln Val Thr Leu Thr Cys Glu Ala Ser Gly Asp Pro Ile 325 330 335 Pro Ser Ile Thr Trp Arg Thr Ser Thr Arg Asn Ile Ser Ser Glu Glu 340 345 350 Lys Thr Leu Asp Gly His Met Val Val Arg Ser His Ala Arg Val Ser 355 360 365 Ser Leu Thr Leu Lys Ser Ile Gln Tyr Thr Asp Ala Gly Glu Tyr Ile 370 375 380 Cys Thr Ala Ser Asn Thr Ile Gly Gln Asp Ser Gln Ser Met Tyr Leu 385 390 395 400 Glu Val Gln Tyr Ala Pro Lys Leu Gln Gly Pro Val Ala Val Tyr Thr 405 410 415 Trp Glu Gly Asn Gln Val Asn Ile Thr Cys Glu Val Phe Ala Tyr Pro 420 425 430 Ser Ala Thr Ile Ser Trp Phe Arg Asp Gly Gln Leu Leu Pro Ser Ser 435 440 445 Asn Tyr Ser Asn Ile Lys Ile Tyr Asn Thr Pro Ser Ala Ser Tyr Leu 450 455 460 Glu Val Thr Pro Asp Ser Glu Asn Asp Phe Gly Asn Tyr Asn Cys Thr 465 470 475 480 Ala Val Asn Arg Ile Gly Gln Glu Ser Leu Glu Phe Ile Leu Val Gln 485 490 495 Ala Asp Thr Pro Ser Ser Pro Ser Ile Asp Gln Val Glu Pro Tyr Ser 500 505 510 Ser Thr Ala Gln Val Gln Phe Asp Glu Pro Glu Ala Thr Gly Gly Val 515 520 525 Pro Ile Leu Lys Tyr Lys Ala Glu Trp Arg Ala Val Gly Glu Glu Val 530 535 540 Trp His Ser Lys Trp Tyr Asp Ala Lys Glu Ala Ser Met Glu Gly Ile 545 550 555 560 Val Thr Ile Val Gly Leu Lys Pro Glu Thr Thr Tyr Ala Val Arg Leu 565 570 575 Ala Ala Leu Asn Gly Lys Gly Leu Gly Glu Ile Ser Ala Ala Ser Glu 580 585 590 Phe Lys Thr Gln Pro Val Arg Glu Pro Ser Ala Pro Lys Leu Glu Gly 595 600 605 Gln Met Gly Glu Asp Gly Asn Ser Ile Lys Val Asn Leu Ile Lys Gln 610 615 620 Asp Asp Gly Gly Ser Pro Ile Arg His Tyr Leu Val Arg Tyr Arg Ala 625 630 635 640 Leu Ser Ser Glu Trp Lys Pro Glu Ile Arg Leu Pro Ser Gly Ser Asp 645 650 655 His Val Met Leu Lys Ser Leu Asp Trp Asn Ala Glu Tyr Glu Val Tyr 660 665 670 Val Val Ala Glu Asn Gln Gln Gly Lys Ser Lys Ala Ala His Phe Val 675 680 685 Phe Arg Thr Ser Ala Gln Pro Thr Ala Ile Pro Ala Asn Gly Ser Pro 690 695 700 Thr Ser Gly Leu Ser Thr Gly Ala Ile Val Gly Ile Leu Ile Val Ile 705 710 715 720 Phe Val Leu Leu Leu Val Val Val Asp Ile Thr Cys Tyr Phe Leu Asn 725 730 735 Lys Cys Gly Leu Phe Met Cys Ile Ala Val Asn Leu Cys Gly Lys Ala 740 745 750 Gly Pro Gly Ala Lys Gly Lys Asp Met Glu Glu Gly Lys Ala Ala Phe 755 760 765 Ser Lys Asp Glu Ser Lys Glu Pro Ile Val Glu Val Arg Thr Glu Glu 770 775 780 Glu Arg Thr Pro Asn His Asp Gly Gly Lys His Thr Glu Pro Asn Glu 785 790 795 800 Thr Thr Pro Leu Thr Glu Pro Glu Lys Gly Pro Val Glu Ala Lys Pro 805 810 815 Glu Cys Gln Glu Thr Glu Thr Lys Pro Ala Pro Ala Glu Val Lys Thr 820 825 830 Val Pro Asn Asp Ala Thr Gln Thr Lys Glu Asn Glu Ser Lys Ala 835 840 845 <![CDATA[<210> 171]]> <![CDATA[<211> 858]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 171]]> Met Leu Gln Thr Lys Asp Leu Ile Trp Thr Leu Phe Phe Leu Gly Thr 1 5 10 15 Ala Val Ser Leu Gln Val Asp Ile Val Pro Ser Gln Gly Glu Ile Ser 20 25 30 Val Gly Glu Ser Lys Phe Phe Leu Cys Gln Val Ala Gly Asp Ala Lys 35 40 45 Asp Lys Asp Ile Ser Trp Phe Ser Pro Asn Gly Glu Lys Leu Thr Pro 50 55 60 Asn Gln Gln Arg Ile Ser Val Val Trp Asn Asp Asp Ser Ser Ser Thr 65 70 75 80 Leu Thr Ile Tyr Asn Ala Asn Ile Asp Asp Ala Gly Ile Tyr Lys Cys 85 90 95 Val Val Thr Gly Glu Asp Gly Ser Glu Ser Glu Ala Thr Val Asn Val 100 105 110 Lys Ile Phe Gln Lys Leu Met Phe Lys Asn Ala Pro Thr Pro Gln Glu 115 120 125 Phe Arg Glu Gly Glu Asp Ala Val Ile Val Cys Asp Val Val Ser Ser 130 135 140 Leu Pro Pro Thr Ile Ile Trp Lys His Lys Gly Arg Asp Val Ile Leu 145 150 155 160 Lys Lys Asp Val Arg Phe Ile Val Leu Ser Asn Asn Tyr Leu Gln Ile 165 170 175 Arg Gly Ile Lys Lys Thr Asp Glu Gly Thr Tyr Arg Cys Glu Gly Arg 180 185 190 Ile Leu Ala Arg Gly Glu Ile Asn Phe Lys Asp Ile Gln Val Ile Val 195 200 205 Asn Val Pro Pro Thr Ile Gln Ala Arg Gln Asn Ile Val Asn Ala Thr 210 215 220 Ala Asn Leu Gly Gln Ser Val Thr Leu Val Cys Asp Ala Glu Gly Phe 225 230 235 240 Pro Glu Pro Thr Met Ser Trp Thr Lys Asp Gly Glu Gln Ile Glu Gln 245 250 255 Glu Glu Asp Asp Glu Lys Tyr Ile Phe Ser Asp Asp Ser Ser Gln Leu 260 265 270 Thr Ile Lys Lys Val Asp Lys Asn Asp Glu Ala Glu Tyr Ile Cys Ile 275 280 285 Ala Glu Asn Lys Ala Gly Glu Gln Asp Ala Thr Ile His Leu Lys Val 290 295 300 Phe Ala Lys Pro Lys Ile Thr Tyr Val Glu Asn Gln Thr Ala Met Glu 305 310 315 320 Leu Glu Glu Gln Val Thr Leu Thr Cys Glu Ala Ser Gly Asp Pro Ile 325 330 335 Pro Ser Ile Thr Trp Arg Thr Ser Thr Arg Asn Ile Ser Ser Glu Glu 340 345 350 Lys Ala Ser Trp Thr Arg Pro Glu Lys Gln Glu Thr Leu Asp Gly His 355 360 365 Met Val Val Arg Ser His Ala Arg Val Ser Ser Leu Thr Leu Lys Ser 370 375 380 Ile Gln Tyr Thr Asp Ala Gly Glu Tyr Ile Cys Thr Ala Ser Asn Thr 385 390 395 400 Ile Gly Gln Asp Ser Gln Ser Met Tyr Leu Glu Val Gln Tyr Ala Pro 405 410 415 Lys Leu Gln Gly Pro Val Ala Val Tyr Thr Trp Glu Gly Asn Gln Val 420 425 430 Asn Ile Thr Cys Glu Val Phe Ala Tyr Pro Ser Ala Thr Ile Ser Trp 435 440 445 Phe Arg Asp Gly Gln Leu Leu Pro Ser Ser Asn Tyr Ser Asn Ile Lys 450 455 460 Ile Tyr Asn Thr Pro Ser Ala Ser Tyr Leu Glu Val Thr Pro Asp Ser 465 470 475 480 Glu Asn Asp Phe Gly Asn Tyr Asn Cys Thr Ala Val Asn Arg Ile Gly 485 490 495 Gln Glu Ser Leu Glu Phe Ile Leu Val Gln Ala Asp Thr Pro Ser Ser 500 505 510 Pro Ser Ile Asp Gln Val Glu Pro Tyr Ser Ser Thr Ala Gln Val Gln 515 520 525 Phe Asp Glu Pro Glu Ala Thr Gly Gly Val Pro Ile Leu Lys Tyr Lys 530 535 540 Ala Glu Trp Arg Ala Val Gly Glu Glu Val Trp His Ser Lys Trp Tyr 545 550 555 560 Asp Ala Lys Glu Ala Ser Met Glu Gly Ile Val Thr Ile Val Gly Leu 565 570 575 Lys Pro Glu Thr Thr Tyr Ala Val Arg Leu Ala Ala Leu Asn Gly Lys 580 585 590 Gly Leu Gly Glu Ile Ser Ala Ala Ser Glu Phe Lys Thr Gln Pro Val 595 600 605 Gln Gly Glu Pro Ser Ala Pro Lys Leu Glu Gly Gln Met Gly Glu Asp 610 615 620 Gly Asn Ser Ile Lys Val Asn Leu Ile Lys Gln Asp Asp Gly Gly Ser 625 630 635 640 Pro Ile Arg His Tyr Leu Val Arg Tyr Arg Ala Leu Ser Ser Glu Trp 645 650 655 Lys Pro Glu Ile Arg Leu Pro Ser Gly Ser Asp His Val Met Leu Lys 660 665 670 Ser Leu Asp Trp Asn Ala Glu Tyr Glu Val Tyr Val Val Ala Glu Asn 675 680 685 Gln Gln Gly Lys Ser Lys Ala Ala His Phe Val Phe Arg Thr Ser Ala 690 695 700 Gln Pro Thr Ala Ile Pro Ala Asn Gly Ser Pro Thr Ser Gly Leu Ser 705 710 715 720 Thr Gly Ala Ile Val Gly Ile Leu Ile Val Ile Phe Val Leu Leu Leu 725 730 735 Val Val Val Asp Ile Thr Cys Tyr Phe Leu Asn Lys Cys Gly Leu Phe 740 745 750 Met Cys Ile Ala Val Asn Leu Cys Gly Lys Ala Gly Pro Gly Ala Lys 755 760 765 Gly Lys Asp Met Glu Glu Gly Lys Ala Ala Phe Ser Lys Asp Glu Ser 770 775 780 Lys Glu Pro Ile Val Glu Val Arg Thr Glu Glu Glu Arg Thr Pro Asn 785 790 795 800 His Asp Gly Gly Lys His Thr Glu Pro Asn Glu Thr Thr Pro Leu Thr 805 810 815 Glu Pro Glu Lys Gly Pro Val Glu Ala Lys Pro Glu Cys Gln Glu Thr 820 825 830 Glu Thr Lys Pro Ala Pro Ala Glu Val Lys Thr Val Pro Asn Asp Ala 835 840 845 Thr Gln Thr Lys Glu Asn Glu Ser Lys Ala 850 855 <![CDATA[<210> 172]]> <![CDATA[<211> 875]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 172]]> Met Phe Leu Leu Arg Arg Tyr Val Cys Ile Phe Thr Glu Lys Leu Lys 1 5 10 15 Asn Gln Ala Glu Leu Tyr Val Phe Leu Ser Val Lys Phe Ser Asn Cys 20 25 30 Asn Gly Lys Arg Lys Val Gln Tyr Glu Ser Ser Glu Pro Ala Asp Phe 35 40 45 Lys Val Asp Glu Asp Gly Met Val Tyr Ala Val Arg Ser Phe Pro Leu 50 55 60 Ser Ser Glu His Ala Lys Phe Leu Ile Tyr Ala Gln Asp Lys Glu Thr 65 70 75 80 Gln Glu Lys Trp Gln Val Ala Val Lys Leu Ser Leu Lys Pro Thr Leu 85 90 95 Thr Glu Glu Ser Val Lys Glu Ser Ala Glu Val Glu Glu Ile Val Phe 100 105 110 Pro Arg Gln Phe Ser Lys His Ser Gly His Leu Gln Arg Gln Lys Arg 115 120 125 Asp Trp Val Ile Pro Pro Ile Asn Leu Pro Glu Asn Ser Arg Gly Pro 130 135 140 Phe Pro Gln Glu Leu Val Arg Ile Arg Ser Asp Arg Asp Lys Asn Leu 145 150 155 160 Ser Leu Arg Tyr Ser Val Thr Gly Pro Gly Ala Asp Gln Pro Pro Thr 165 170 175 Gly Ile Phe Ile Ile Asn Pro Ile Ser Gly Gln Leu Ser Val Thr Lys 180 185 190 Pro Leu Asp Arg Glu Gln Ile Ala Arg Phe His Leu Arg Ala His Ala 195 200 205 Val Asp Ile Asn Gly Asn Gln Val Glu Asn Pro Ile Asp Ile Val Ile 210 215 220 Asn Val Ile Asp Met Asn Asp Asn Arg Pro Glu Phe Leu His Gln Val 225 230 235 240 Trp Asn Gly Thr Val Pro Glu Gly Ser Lys Pro Gly Thr Tyr Val Met 245 250 255 Thr Val Thr Ala Ile Asp Ala Asp Asp Pro Asn Ala Leu Asn Gly Met 260 265 270 Leu Arg Tyr Arg Ile Val Ser Gln Ala Pro Ser Thr Pro Ser Pro Asn 275 280 285 Met Phe Thr Ile Asn Asn Glu Thr Gly Asp Ile Ile Thr Val Ala Ala 290 295 300 Gly Leu Asp Arg Glu Lys Val Gln Gln Tyr Thr Leu Ile Ile Gln Ala 305 310 315 320 Thr Asp Met Glu Gly Asn Pro Thr Tyr Gly Leu Ser Asn Thr Ala Thr 325 330 335 Ala Val Ile Thr Val Thr Asp Val Asn Asp Asn Pro Pro Glu Phe Thr 340 345 350 Ala Met Thr Phe Tyr Gly Glu Val Pro Glu Asn Arg Val Asp Ile Ile 355 360 365 Val Ala Asn Leu Thr Val Thr Asp Lys Asp Gln Pro His Thr Pro Ala 370 375 380 Trp Asn Ala Val Tyr Arg Ile Ser Gly Gly Asp Pro Thr Gly Arg Phe 385 390 395 400 Ala Ile Gln Thr Asp Pro Asn Ser Asn Asp Gly Leu Val Thr Val Val 405 410 415 Lys Pro Ile Asp Phe Glu Thr Asn Arg Met Phe Val Leu Thr Val Ala 420 425 430 Ala Glu Asn Gln Val Pro Leu Ala Lys Gly Ile Gln His Pro Pro Gln 435 440 445 Ser Thr Ala Thr Val Ser Val Thr Val Ile Asp Val Asn Glu Asn Pro 450 455 460 Tyr Phe Ala Pro Asn Pro Lys Ile Ile Arg Gln Glu Glu Gly Leu His 465 470 475 480 Ala Gly Thr Met Leu Thr Thr Phe Thr Ala Gln Asp Pro Asp Arg Tyr 485 490 495 Met Gln Gln Asn Ile Arg Tyr Thr Lys Leu Ser Asp Pro Ala Asn Trp 500 505 510 Leu Lys Ile Asp Pro Val Asn Gly Gln Ile Thr Thr Ile Ala Val Leu 515 520 525 Asp Arg Glu Ser Pro Asn Val Lys Asn Asn Ile Tyr Asn Ala Thr Phe 530 535 540 Leu Ala Ser Asp Asn Gly Ile Pro Pro Met Ser Gly Thr Gly Thr Leu 545 550 555 560 Gln Ile Tyr Leu Leu Asp Ile Asn Asp Asn Ala Pro Gln Val Leu Pro 565 570 575 Gln Glu Ala Glu Thr Cys Glu Thr Pro Asp Pro Asn Ser Ile Asn Ile 580 585 590 Thr Ala Leu Asp Tyr Asp Ile Asp Pro Asn Ala Gly Pro Phe Ala Phe 595 600 605 Asp Leu Pro Leu Ser Pro Val Thr Ile Lys Arg Asn Trp Thr Ile Thr 610 615 620 Arg Leu Asn Gly Asp Phe Ala Gln Leu Asn Leu Lys Ile Lys Phe Leu 625 630 635 640 Glu Ala Gly Ile Tyr Glu Val Pro Ile Ile Ile Thr Asp Ser Gly Asn 645 650 655 Pro Pro Lys Ser Asn Ile Ser Ile Leu Arg Val Lys Val Cys Gln Cys 660 665 670 Asp Ser Asn Gly Asp Cys Thr Asp Val Asp Arg Ile Val Gly Ala Gly 675 680 685 Leu Gly Thr Gly Ala Ile Ile Ala Ile Leu Leu Cys Ile Ile Ile Leu 690 695 700 Leu Ile Leu Val Leu Met Phe Val Val Trp Met Lys Arg Arg Asp Lys 705 710 715 720 Glu Arg Gln Ala Lys Gln Leu Leu Ile Asp Pro Glu Asp Asp Val Arg 725 730 735 Asp Asn Ile Leu Lys Tyr Asp Glu Glu Gly Gly Gly Glu Glu Asp Gln 740 745 750 Asp Tyr Asp Leu Ser Gln Leu Gln Gln Pro Asp Thr Val Glu Pro Asp 755 760 765 Ala Ile Lys Pro Val Gly Ile Arg Arg Met Asp Glu Arg Pro Ile His 770 775 780 Ala Glu Pro Gln Tyr Pro Val Arg Ser Ala Ala Pro His Pro Gly Asp 785 790 795 800 Ile Gly Asp Phe Ile Asn Glu Gly Leu Lys Ala Ala Asp Asn Asp Pro 805 810 815 Thr Ala Pro Pro Tyr Asp Ser Leu Leu Val Phe Asp Tyr Glu Gly Ser 820 825 830 Gly Ser Thr Ala Gly Ser Leu Ser Ser Leu Asn Ser Ser Ser Ser Gly 835 840 845 Gly Glu Gln Asp Tyr Asp Tyr Leu Asn Asp Trp Gly Pro Arg Phe Lys 850 855 860 Lys Leu Ala Asp Met Tyr Gly Gly Gly Asp Asp 865 870 875 <![CDATA[<210> 173]]> <![CDATA[<211> 906]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 173]]> Met Cys Arg Ile Ala Gly Ala Leu Arg Thr Leu Leu Pro Leu Leu Ala 1 5 10 15 Ala Leu Leu Gln Ala Ser Val Glu Ala Ser Gly Glu Ile Ala Leu Cys 20 25 30 Lys Thr Gly Phe Pro Glu Asp Val Tyr Ser Ala Val Leu Ser Lys Asp 35 40 45 Val His Glu Gly Gln Pro Leu Leu Asn Val Lys Phe Ser Asn Cys Asn 50 55 60 Gly Lys Arg Lys Val Gln Tyr Glu Ser Ser Glu Pro Ala Asp Phe Lys 65 70 75 80 Val Asp Glu Asp Gly Met Val Tyr Ala Val Arg Ser Phe Pro Leu Ser 85 90 95 Ser Glu His Ala Lys Phe Leu Ile Tyr Ala Gln Asp Lys Glu Thr Gln 100 105 110 Glu Lys Trp Gln Val Ala Val Lys Leu Ser Leu Lys Pro Thr Leu Thr 115 120 125 Glu Glu Ser Val Lys Glu Ser Ala Glu Val Glu Glu Ile Val Phe Pro 130 135 140 Arg Gln Phe Ser Lys His Ser Gly His Leu Gln Arg Gln Lys Arg Asp 145 150 155 160 Trp Val Ile Pro Pro Ile Asn Leu Pro Glu Asn Ser Arg Gly Pro Phe 165 170 175 Pro Gln Glu Leu Val Arg Ile Arg Ser Asp Arg Asp Lys Asn Leu Ser 180 185 190 Leu Arg Tyr Ser Val Thr Gly Pro Gly Ala Asp Gln Pro Pro Thr Gly 195 200 205 Ile Phe Ile Ile Asn Pro Ile Ser Gly Gln Leu Ser Val Thr Lys Pro 210 215 220 Leu Asp Arg Glu Gln Ile Ala Arg Phe His Leu Arg Ala His Ala Val 225 230 235 240 Asp Ile Asn Gly Asn Gln Val Glu Asn Pro Ile Asp Ile Val Ile Asn 245 250 255 Val Ile Asp Met Asn Asp Asn Arg Pro Glu Phe Leu His Gln Val Trp 260 265 270 Asn Gly Thr Val Pro Glu Gly Ser Lys Pro Gly Thr Tyr Val Met Thr 275 280 285 Val Thr Ala Ile Asp Ala Asp Asp Pro Asn Ala Leu Asn Gly Met Leu 290 295 300 Arg Tyr Arg Ile Val Ser Gln Ala Pro Ser Thr Pro Ser Pro Asn Met 305 310 315 320 Phe Thr Ile Asn Asn Glu Thr Gly Asp Ile Ile Thr Val Ala Ala Gly 325 330 335 Leu Asp Arg Glu Lys Val Gln Gln Tyr Thr Leu Ile Ile Gln Ala Thr 340 345 350 Asp Met Glu Gly Asn Pro Thr Tyr Gly Leu Ser Asn Thr Ala Thr Ala 355 360 365 Val Ile Thr Val Thr Asp Val Asn Asp Asn Pro Pro Glu Phe Thr Ala 370 375 380 Met Thr Phe Tyr Gly Glu Val Pro Glu Asn Arg Val Asp Ile Ile Val 385 390 395 400 Ala Asn Leu Thr Val Thr Asp Lys Asp Gln Pro His Thr Pro Ala Trp 405 410 415 Asn Ala Val Tyr Arg Ile Ser Gly Gly Asp Pro Thr Gly Arg Phe Ala 420 425 430 Ile Gln Thr Asp Pro Asn Ser Asn Asp Gly Leu Val Thr Val Val Lys 435 440 445 Pro Ile Asp Phe Glu Thr Asn Arg Met Phe Val Leu Thr Val Ala Ala 450 455 460 Glu Asn Gln Val Pro Leu Ala Lys Gly Ile Gln His Pro Pro Gln Ser 465 470 475 480 Thr Ala Thr Val Ser Val Thr Val Ile Asp Val Asn Glu Asn Pro Tyr 485 490 495 Phe Ala Pro Asn Pro Lys Ile Ile Arg Gln Glu Glu Gly Leu His Ala 500 505 510 Gly Thr Met Leu Thr Thr Phe Thr Ala Gln Asp Pro Asp Arg Tyr Met 515 520 525 Gln Gln Asn Ile Arg Tyr Thr Lys Leu Ser Asp Pro Ala Asn Trp Leu 530 535 540 Lys Ile Asp Pro Val Asn Gly Gln Ile Thr Thr Ile Ala Val Leu Asp 545 550 555 560 Arg Glu Ser Pro Asn Val Lys Asn Asn Ile Tyr Asn Ala Thr Phe Leu 565 570 575 Ala Ser Asp Asn Gly Ile Pro Pro Met Ser Gly Thr Gly Thr Leu Gln 580 585 590 Ile Tyr Leu Leu Asp Ile Asn Asp Asn Ala Pro Gln Val Leu Pro Gln 595 600 605 Glu Ala Glu Thr Cys Glu Thr Pro Asp Pro Asn Ser Ile Asn Ile Thr 610 615 620 Ala Leu Asp Tyr Asp Ile Asp Pro Asn Ala Gly Pro Phe Ala Phe Asp 625 630 635 640 Leu Pro Leu Ser Pro Val Thr Ile Lys Arg Asn Trp Thr Ile Thr Arg 645 650 655 Leu Asn Gly Asp Phe Ala Gln Leu Asn Leu Lys Ile Lys Phe Leu Glu 660 665 670 Ala Gly Ile Tyr Glu Val Pro Ile Ile Ile Thr Asp Ser Gly Asn Pro 675 680 685 Pro Lys Ser Asn Ile Ser Ile Leu Arg Val Lys Val Cys Gln Cys Asp 690 695 700 Ser Asn Gly Asp Cys Thr Asp Val Asp Arg Ile Val Gly Ala Gly Leu 705 710 715 720 Gly Thr Gly Ala Ile Ile Ala Ile Leu Leu Cys Ile Ile Ile Leu Leu 725 730 735 Ile Leu Val Leu Met Phe Val Val Trp Met Lys Arg Arg Asp Lys Glu 740 745 750 Arg Gln Ala Lys Gln Leu Leu Ile Asp Pro Glu Asp Asp Val Arg Asp 755 760 765 Asn Ile Leu Lys Tyr Asp Glu Glu Gly Gly Gly Glu Glu Asp Gln Asp 770 775 780 Tyr Asp Leu Ser Gln Leu Gln Gln Pro Asp Thr Val Glu Pro Asp Ala 785 790 795 800 Ile Lys Pro Val Gly Ile Arg Arg Met Asp Glu Arg Pro Ile His Ala 805 810 815 Glu Pro Gln Tyr Pro Val Arg Ser Ala Ala Pro His Pro Gly Asp Ile 820 825 830 Gly Asp Phe Ile Asn Glu Gly Leu Lys Ala Ala Asp Asn Asp Pro Thr 835 840 845 Ala Pro Pro Tyr Asp Ser Leu Leu Val Phe Asp Tyr Glu Gly Ser Gly 850 855 860 Ser Thr Ala Gly Ser Leu Ser Ser Leu Asn Ser Ser Ser Ser Gly Gly 865 870 875 880 Glu Gln Asp Tyr Asp Tyr Leu Asn Asp Trp Gly Pro Arg Phe Lys Lys 885 890 895 Leu Ala Asp Met Tyr Gly Gly Gly Asp Asp 900 905 <![CDATA[<210> 174]]> <![CDATA[<211> 1079]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 174]]> Met Glu Asp Glu Ala Val Leu Asp Arg Gly Ala Ser Phe Leu Lys His 1 5 10 15 Val Cys Asp Glu Glu Glu Val Glu Gly His His Thr Ile Tyr Ile Gly 20 25 30 Val His Val Pro Lys Ser Tyr Arg Arg Arg Arg Arg His Lys Arg Lys 35 40 45 Thr Gly His Lys Glu Lys Lys Glu Lys Glu Arg Ile Ser Glu Asn Tyr 50 55 60 Ser Asp Lys Ser Asp Ile Glu Asn Ala Asp Glu Ser Ser Ser Ser Ile 65 70 75 80 Leu Lys Pro Leu Ile Ser Pro Ala Ala Glu Arg Ile Arg Phe Ile Leu 85 90 95 Gly Glu Glu Asp Asp Ser Pro Ala Pro Pro Gln Leu Phe Thr Glu Leu 100 105 110 Asp Glu Leu Leu Ala Val Asp Gly Gln Glu Met Glu Trp Lys Glu Thr 115 120 125 Ala Arg Trp Ile Lys Phe Glu Glu Lys Val Glu Gln Gly Gly Glu Arg 130 135 140 Trp Ser Lys Pro His Val Ala Thr Leu Ser Leu His Ser Leu Phe Glu 145 150 155 160 Leu Arg Thr Cys Met Glu Lys Gly Ser Ile Met Leu Asp Arg Glu Ala 165 170 175 Ser Ser Leu Pro Gln Leu Val Glu Met Ile Val Asp His Gln Ile Glu 180 185 190 Thr Gly Leu Leu Lys Pro Glu Leu Lys Asp Lys Val Thr Tyr Thr Leu 195 200 205 Leu Arg Lys His Arg His Gln Thr Lys Lys Ser Asn Leu Arg Ser Leu 210 215 220 Ala Asp Ile Gly Lys Thr Val Ser Ser Ala Ser Arg Met Phe Thr Asn 225 230 235 240 Pro Asp Asn Gly Ser Pro Ala Met Thr His Arg Asn Leu Thr Ser Ser 245 250 255 Ser Leu Asn Asp Ile Ser Asp Lys Pro Glu Lys Asp Gln Leu Lys Asn 260 265 270 Lys Phe Met Lys Lys Leu Pro Arg Asp Ala Glu Ala Ser Asn Val Leu 275 280 285 Val Gly Glu Val Asp Phe Leu Asp Thr Pro Phe Ile Ala Phe Val Arg 290 295 300 Leu Gln Gln Ala Val Met Leu Gly Ala Leu Thr Glu Val Pro Val Pro 305 310 315 320 Thr Arg Phe Leu Phe Ile Leu Leu Gly Pro Lys Gly Lys Ala Lys Ser 325 330 335 Tyr His Glu Ile Gly Arg Ala Ile Ala Thr Leu Met Ser Asp Glu Val 340 345 350 Phe His Asp Ile Ala Tyr Lys Ala Lys Asp Arg His Asp Leu Ile Ala 355 360 365 Gly Ile Asp Glu Phe Leu Asp Glu Val Ile Val Leu Pro Pro Gly Glu 370 375 380 Trp Asp Pro Ala Ile Arg Ile Glu Pro Pro Lys Ser Leu Pro Ser Ser 385 390 395 400 Asp Lys Arg Lys Asn Met Tyr Ser Gly Gly Glu Asn Val Gln Met Asn 405 410 415 Gly Asp Thr Pro His Asp Gly Gly His Gly Gly Gly Gly His Gly Asp 420 425 430 Cys Glu Glu Leu Gln Arg Thr Gly Arg Phe Cys Gly Gly Leu Ile Lys 435 440 445 Asp Ile Lys Arg Lys Ala Pro Phe Phe Ala Ser Asp Phe Tyr Asp Ala 450 455 460 Leu Asn Ile Gln Ala Leu Ser Ala Ile Leu Phe Ile Tyr Leu Ala Thr 465 470 475 480 Val Thr Asn Ala Ile Thr Phe Gly Gly Leu Leu Gly Asp Ala Thr Asp 485 490 495 Asn Met Gln Gly Val Leu Glu Ser Phe Leu Gly Thr Ala Val Ser Gly 500 505 510 Ala Ile Phe Cys Leu Phe Ala Gly Gln Pro Leu Thr Ile Leu Ser Ser 515 520 525 Thr Gly Pro Val Leu Val Phe Glu Arg Leu Leu Phe Asn Phe Ser Lys 530 535 540 Asp Asn Asn Phe Asp Tyr Leu Glu Phe Arg Leu Trp Ile Gly Leu Trp 545 550 555 560 Ser Ala Phe Leu Cys Leu Ile Leu Val Ala Thr Asp Ala Ser Phe Leu 565 570 575 Val Gln Tyr Phe Thr Arg Phe Thr Glu Glu Gly Phe Ser Ser Leu Ile 580 585 590 Ser Phe Ile Phe Ile Tyr Asp Ala Phe Lys Lys Met Ile Lys Leu Ala 595 600 605 Asp Tyr Tyr Pro Ile Asn Ser Asn Phe Lys Val Gly Tyr Asn Thr Leu 610 615 620 Phe Ser Cys Thr Cys Val Pro Pro Asp Pro Ala Asn Ile Ser Ile Ser 625 630 635 640 Asn Asp Thr Thr Leu Ala Pro Glu Tyr Leu Pro Thr Met Ser Ser Thr 645 650 655 Asp Met Tyr His Asn Thr Thr Phe Asp Trp Ala Phe Leu Ser Lys Lys 660 665 670 Glu Cys Ser Lys Tyr Gly Gly Asn Leu Val Gly Asn Asn Cys Asn Phe 675 680 685 Val Pro Asp Ile Thr Leu Met Ser Phe Ile Leu Phe Leu Gly Thr Tyr 690 695 700 Thr Ser Ser Met Ala Leu Lys Lys Phe Lys Thr Ser Pro Tyr Phe Pro 705 710 715 720 Thr Thr Ala Arg Lys Leu Ile Ser Asp Phe Ala Ile Ile Leu Ser Ile 725 730 735 Leu Ile Phe Cys Val Ile Asp Ala Leu Val Gly Val Asp Thr Pro Lys 740 745 750 Leu Ile Val Pro Ser Glu Phe Lys Pro Thr Ser Pro Asn Arg Gly Trp 755 760 765 Phe Val Pro Pro Phe Gly Glu Asn Pro Trp Trp Val Cys Leu Ala Ala 770 775 780 Ala Ile Pro Ala Leu Leu Val Thr Ile Leu Ile Phe Met Asp Gln Gln 785 790 795 800 Ile Thr Ala Val Ile Val Asn Arg Lys Glu His Lys Leu Lys Lys Gly 805 810 815 Ala Gly Tyr His Leu Asp Leu Phe Trp Val Ala Ile Leu Met Val Ile 820 825 830 Cys Ser Leu Met Ala Leu Pro Trp Tyr Val Ala Ala Thr Val Ile Ser 835 840 845 Ile Ala His Ile Asp Ser Leu Lys Met Glu Thr Glu Thr Ser Ala Pro 850 855 860 Gly Glu Gln Pro Lys Phe Leu Gly Val Arg Glu Gln Arg Val Thr Gly 865 870 875 880 Thr Leu Val Phe Ile Leu Thr Gly Leu Ser Val Phe Met Ala Pro Ile 885 890 895 Leu Lys Phe Ile Pro Met Pro Val Leu Tyr Gly Val Phe Leu Tyr Met 900 905 910 Gly Val Ala Ser Leu Asn Gly Val Gln Phe Met Asp Arg Leu Lys Leu 915 920 925 Leu Leu Met Pro Leu Lys His Gln Pro Asp Phe Ile Tyr Leu Arg His 930 935 940 Val Pro Leu Arg Arg Val His Leu Phe Thr Phe Leu Gln Val Leu Cys 945 950 955 960 Leu Ala Leu Leu Trp Ile Leu Lys Ser Thr Val Ala Ala Ile Ile Phe 965 970 975 Pro Val Met Ile Leu Ala Leu Val Ala Val Arg Lys Gly Met Asp Tyr 980 985 990 Leu Phe Ser Gln His Asp Leu Ser Phe Leu Asp Asp Val Ile Pro Glu 995 1000 1005 Lys Asp Lys Lys Lys Lys Glu Asp Glu Lys Lys Lys Lys Lys Lys 1010 1015 1020 Lys Gly Ser Leu Asp Ser Asp Asn Asp Asp Ser Asp Cys Pro Tyr 1025 1030 1035 Ser Glu Lys Val Pro Ser Ile Lys Ile Pro Met Asp Ile Met Glu 1040 1045 1050 Gln Gln Pro Phe Leu Ser Asp Ser Lys Pro Ser Asp Arg Glu Arg 1055 1060 1065 Ser Pro Thr Phe Leu Glu Arg His Thr Ser Cys 1070 1075 <![CDATA[<210> 175]]> <![CDATA[<211> 1094]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 175]]> Met Glu Asp Glu Ala Val Leu Asp Arg Gly Ala Ser Phe Leu Lys His 1 5 10 15 Val Cys Asp Glu Glu Glu Val Glu Gly His His Thr Ile Tyr Ile Gly 20 25 30 Val His Val Pro Lys Ser Tyr Arg Arg Arg Arg Arg His Lys Arg Lys 35 40 45 Thr Gly His Lys Glu Lys Lys Glu Lys Glu Arg Ile Ser Glu Asn Tyr 50 55 60 Ser Asp Lys Ser Asp Ile Glu Asn Ala Asp Glu Ser Ser Ser Ser Ile 65 70 75 80 Leu Lys Pro Leu Ile Ser Pro Ala Ala Glu Arg Ile Arg Phe Ile Leu 85 90 95 Gly Glu Glu Asp Asp Ser Pro Ala Pro Pro Gln Leu Phe Thr Glu Leu 100 105 110 Asp Glu Leu Leu Ala Val Asp Gly Gln Glu Met Glu Trp Lys Glu Thr 115 120 125 Ala Arg Trp Ile Lys Phe Glu Glu Lys Val Glu Gln Gly Gly Glu Arg 130 135 140 Trp Ser Lys Pro His Val Ala Thr Leu Ser Leu His Ser Leu Phe Glu 145 150 155 160 Leu Arg Thr Cys Met Glu Lys Gly Ser Ile Met Leu Asp Arg Glu Ala 165 170 175 Ser Ser Leu Pro Gln Leu Val Glu Met Ile Val Asp His Gln Ile Glu 180 185 190 Thr Gly Leu Leu Lys Pro Glu Leu Lys Asp Lys Val Thr Tyr Thr Leu 195 200 205 Leu Arg Lys His Arg His Gln Thr Lys Lys Ser Asn Leu Arg Ser Leu 210 215 220 Ala Asp Ile Gly Lys Thr Val Ser Ser Ala Ser Arg Met Phe Thr Asn 225 230 235 240 Pro Asp Asn Gly Ser Pro Ala Met Thr His Arg Asn Leu Thr Ser Ser 245 250 255 Ser Leu Asn Asp Ile Ser Asp Lys Pro Glu Lys Asp Gln Leu Lys Asn 260 265 270 Lys Phe Met Lys Lys Leu Pro Arg Asp Ala Glu Ala Ser Asn Val Leu 275 280 285 Val Gly Glu Val Asp Phe Leu Asp Thr Pro Phe Ile Ala Phe Val Arg 290 295 300 Leu Gln Gln Ala Val Met Leu Gly Ala Leu Thr Glu Val Pro Val Pro 305 310 315 320 Thr Arg Phe Leu Phe Ile Leu Leu Gly Pro Lys Gly Lys Ala Lys Ser 325 330 335 Tyr His Glu Ile Gly Arg Ala Ile Ala Thr Leu Met Ser Asp Glu Val 340 345 350 Phe His Asp Ile Ala Tyr Lys Ala Lys Asp Arg His Asp Leu Ile Ala 355 360 365 Gly Ile Asp Glu Phe Leu Asp Glu Val Ile Val Leu Pro Pro Gly Glu 370 375 380 Trp Asp Pro Ala Ile Arg Ile Glu Pro Pro Lys Ser Leu Pro Ser Ser 385 390 395 400 Asp Lys Arg Lys Asn Met Tyr Ser Gly Gly Glu Asn Val Gln Met Asn 405 410 415 Gly Asp Thr Pro His Asp Gly Gly His Gly Gly Gly Gly His Gly Asp 420 425 430 Cys Glu Glu Leu Gln Arg Thr Gly Arg Phe Cys Gly Gly Leu Ile Lys 435 440 445 Asp Ile Lys Arg Lys Ala Pro Phe Phe Ala Ser Asp Phe Tyr Asp Ala 450 455 460 Leu Asn Ile Gln Ala Leu Ser Ala Ile Leu Phe Ile Tyr Leu Ala Thr 465 470 475 480 Val Thr Asn Ala Ile Thr Phe Gly Gly Leu Leu Gly Asp Ala Thr Asp 485 490 495 Asn Met Gln Gly Val Leu Glu Ser Phe Leu Gly Thr Ala Val Ser Gly 500 505 510 Ala Ile Phe Cys Leu Phe Ala Gly Gln Pro Leu Thr Ile Leu Ser Ser 515 520 525 Thr Gly Pro Val Leu Val Phe Glu Arg Leu Leu Phe Asn Phe Ser Lys 530 535 540 Asp Asn Asn Phe Asp Tyr Leu Glu Phe Arg Leu Trp Ile Gly Leu Trp 545 550 555 560 Ser Ala Phe Leu Cys Leu Ile Leu Val Ala Thr Asp Ala Ser Phe Leu 565 570 575 Val Gln Tyr Phe Thr Arg Phe Thr Glu Glu Gly Phe Ser Ser Leu Ile 580 585 590 Ser Phe Ile Phe Ile Tyr Asp Ala Phe Lys Lys Met Ile Lys Leu Ala 595 600 605 Asp Tyr Tyr Pro Ile Asn Ser Asn Phe Lys Val Gly Tyr Asn Thr Leu 610 615 620 Phe Ser Cys Thr Cys Val Pro Pro Asp Pro Ala Asn Ile Ser Ile Ser 625 630 635 640 Asn Asp Thr Thr Leu Ala Pro Glu Tyr Leu Pro Thr Met Ser Ser Thr 645 650 655 Asp Met Tyr His Asn Thr Thr Phe Asp Trp Ala Phe Leu Ser Lys Lys 660 665 670 Glu Cys Ser Lys Tyr Gly Gly Asn Leu Val Gly Asn Asn Cys Asn Phe 675 680 685 Val Pro Asp Ile Thr Leu Met Ser Phe Ile Leu Phe Leu Gly Thr Tyr 690 695 700 Thr Ser Ser Met Ala Leu Lys Lys Phe Lys Thr Ser Pro Tyr Phe Pro 705 710 715 720 Thr Thr Ala Arg Lys Leu Ile Ser Asp Phe Ala Ile Ile Leu Ser Ile 725 730 735 Leu Ile Phe Cys Val Ile Asp Ala Leu Val Gly Val Asp Thr Pro Lys 740 745 750 Leu Ile Val Pro Ser Glu Phe Lys Pro Thr Ser Pro Asn Arg Gly Trp 755 760 765 Phe Val Pro Pro Phe Gly Glu Asn Pro Trp Trp Val Cys Leu Ala Ala 770 775 780 Ala Ile Pro Ala Leu Leu Val Thr Ile Leu Ile Phe Met Asp Gln Gln 785 790 795 800 Ile Thr Ala Val Ile Val Asn Arg Lys Glu His Lys Leu Lys Lys Gly 805 810 815 Ala Gly Tyr His Leu Asp Leu Phe Trp Val Ala Ile Leu Met Val Ile 820 825 830 Cys Ser Leu Met Ala Leu Pro Trp Tyr Val Ala Ala Thr Val Ile Ser 835 840 845 Ile Ala His Ile Asp Ser Leu Lys Met Glu Thr Glu Thr Ser Ala Pro 850 855 860 Gly Glu Gln Pro Lys Phe Leu Gly Val Arg Glu Gln Arg Val Thr Gly 865 870 875 880 Thr Leu Val Phe Ile Leu Thr Gly Leu Ser Val Phe Met Ala Pro Ile 885 890 895 Leu Lys Phe Ile Pro Met Pro Val Leu Tyr Gly Val Phe Leu Tyr Met 900 905 910 Gly Val Ala Ser Leu Asn Gly Val Gln Phe Met Asp Arg Leu Lys Leu 915 920 925 Leu Leu Met Pro Leu Lys His Gln Pro Asp Phe Ile Tyr Leu Arg His 930 935 940 Val Pro Leu Arg Arg Val His Leu Phe Thr Phe Leu Gln Val Leu Cys 945 950 955 960 Leu Ala Leu Leu Trp Ile Leu Lys Ser Thr Val Ala Ala Ile Ile Phe 965 970 975 Pro Val Met Ile Leu Ala Leu Val Ala Val Arg Lys Gly Met Asp Tyr 980 985 990 Leu Phe Ser Gln His Asp Leu Ser Phe Leu Asp Asp Val Ile Pro Glu 995 1000 1005 Lys Asp Lys Lys Lys Lys Glu Asp Glu Lys Lys Lys Lys Lys Lys 1010 1015 1020 Lys Gly Ser Leu Asp Ser Asp Asn Asp Asp Glu Lys Asp His Gln 1025 1030 1035 His Ser Leu Asn Ala Thr His His Ala Asp Lys Ile Pro Phe Leu 1040 1045 1050 Gln Ser Leu Gly Met Pro Ser Pro Pro Arg Thr Pro Val Lys Val 1055 1060 1065 Val Pro Gln Ile Arg Ile Glu Leu Glu Pro Glu Asp Asn Asp Tyr 1070 1075 1080 Phe Trp Arg Ser Lys Gly Thr Glu Thr Thr Leu 1085 1090 <![CDATA[<210> 176]]> <![CDATA[<211> 1035]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 176]]> Met Ser Thr Glu Asn Val Glu Gly Lys Pro Ser Asn Leu Gly Glu Arg 1 5 10 15 Gly Arg Ala Arg Ser Ser Thr Phe Leu Arg Val Val Gln Pro Met Phe 20 25 30 Asn His Ser Ile Phe Thr Ser Ala Val Ser Pro Ala Ala Glu Arg Ile 35 40 45 Arg Phe Ile Leu Gly Glu Glu Asp Asp Ser Pro Ala Pro Pro Gln Leu 50 55 60 Phe Thr Glu Leu Asp Glu Leu Leu Ala Val Asp Gly Gln Glu Met Glu 65 70 75 80 Trp Lys Glu Thr Ala Arg Trp Ile Lys Phe Glu Glu Lys Val Glu Gln 85 90 95 Gly Gly Glu Arg Trp Ser Lys Pro His Val Ala Thr Leu Ser Leu His 100 105 110 Ser Leu Phe Glu Leu Arg Thr Cys Met Glu Lys Gly Ser Ile Met Leu 115 120 125 Asp Arg Glu Ala Ser Ser Leu Pro Gln Leu Val Glu Met Ile Val Asp 130 135 140 His Gln Ile Glu Thr Gly Leu Leu Lys Pro Glu Leu Lys Asp Lys Val 145 150 155 160 Thr Tyr Thr Leu Leu Arg Lys His Arg His Gln Thr Lys Lys Ser Asn 165 170 175 Leu Arg Ser Leu Ala Asp Ile Gly Lys Thr Val Ser Ser Ala Ser Arg 180 185 190 Met Phe Thr Asn Pro Asp Asn Gly Ser Pro Ala Met Thr His Arg Asn 195 200 205 Leu Thr Ser Ser Ser Leu Asn Asp Ile Ser Asp Lys Pro Glu Lys Asp 210 215 220 Gln Leu Lys Asn Lys Phe Met Lys Lys Leu Pro Arg Asp Ala Glu Ala 225 230 235 240 Ser Asn Val Leu Val Gly Glu Val Asp Phe Leu Asp Thr Pro Phe Ile 245 250 255 Ala Phe Val Arg Leu Gln Gln Ala Val Met Leu Gly Ala Leu Thr Glu 260 265 270 Val Pro Val Pro Thr Arg Phe Leu Phe Ile Leu Leu Gly Pro Lys Gly 275 280 285 Lys Ala Lys Ser Tyr His Glu Ile Gly Arg Ala Ile Ala Thr Leu Met 290 295 300 Ser Asp Glu Val Phe His Asp Ile Ala Tyr Lys Ala Lys Asp Arg His 305 310 315 320 Asp Leu Ile Ala Gly Ile Asp Glu Phe Leu Asp Glu Val Ile Val Leu 325 330 335 Pro Pro Gly Glu Trp Asp Pro Ala Ile Arg Ile Glu Pro Pro Lys Ser 340 345 350 Leu Pro Ser Ser Asp Lys Arg Lys Asn Met Tyr Ser Gly Gly Glu Asn 355 360 365 Val Gln Met Asn Gly Asp Thr Pro His Asp Gly Gly His Gly Gly Gly 370 375 380 Gly His Gly Asp Cys Glu Glu Leu Gln Arg Thr Gly Arg Phe Cys Gly 385 390 395 400 Gly Leu Ile Lys Asp Ile Lys Arg Lys Ala Pro Phe Phe Ala Ser Asp 405 410 415 Phe Tyr Asp Ala Leu Asn Ile Gln Ala Leu Ser Ala Ile Leu Phe Ile 420 425 430 Tyr Leu Ala Thr Val Thr Asn Ala Ile Thr Phe Gly Gly Leu Leu Gly 435 440 445 Asp Ala Thr Asp Asn Met Gln Gly Val Leu Glu Ser Phe Leu Gly Thr 450 455 460 Ala Val Ser Gly Ala Ile Phe Cys Leu Phe Ala Gly Gln Pro Leu Thr 465 470 475 480 Ile Leu Ser Ser Thr Gly Pro Val Leu Val Phe Glu Arg Leu Leu Phe 485 490 495 Asn Phe Ser Lys Asp Asn Asn Phe Asp Tyr Leu Glu Phe Arg Leu Trp 500 505 510 Ile Gly Leu Trp Ser Ala Phe Leu Cys Leu Ile Leu Val Ala Thr Asp 515 520 525 Ala Ser Phe Leu Val Gln Tyr Phe Thr Arg Phe Thr Glu Glu Gly Phe 530 535 540 Ser Ser Leu Ile Ser Phe Ile Phe Ile Tyr Asp Ala Phe Lys Lys Met 545 550 555 560 Ile Lys Leu Ala Asp Tyr Tyr Pro Ile Asn Ser Asn Phe Lys Val Gly 565 570 575 Tyr Asn Thr Leu Phe Ser Cys Thr Cys Val Pro Pro Asp Pro Ala Asn 580 585 590 Ile Ser Ile Ser Asn Asp Thr Thr Leu Ala Pro Glu Tyr Leu Pro Thr 595 600 605 Met Ser Ser Thr Asp Met Tyr His Asn Thr Thr Phe Asp Trp Ala Phe 610 615 620 Leu Ser Lys Lys Glu Cys Ser Lys Tyr Gly Gly Asn Leu Val Gly Asn 625 630 635 640 Asn Cys Asn Phe Val Pro Asp Ile Thr Leu Met Ser Phe Ile Leu Phe 645 650 655 Leu Gly Thr Tyr Thr Ser Ser Met Ala Leu Lys Lys Phe Lys Thr Ser 660 665 670 Pro Tyr Phe Pro Thr Thr Ala Arg Lys Leu Ile Ser Asp Phe Ala Ile 675 680 685 Ile Leu Ser Ile Leu Ile Phe Cys Val Ile Asp Ala Leu Val Gly Val 690 695 700 Asp Thr Pro Lys Leu Ile Val Pro Ser Glu Phe Lys Pro Thr Ser Pro 705 710 715 720 Asn Arg Gly Trp Phe Val Pro Pro Phe Gly Glu Asn Pro Trp Trp Val 725 730 735 Cys Leu Ala Ala Ala Ile Pro Ala Leu Leu Val Thr Ile Leu Ile Phe 740 745 750 Met Asp Gln Gln Ile Thr Ala Val Ile Val Asn Arg Lys Glu His Lys 755 760 765 Leu Lys Lys Gly Ala Gly Tyr His Leu Asp Leu Phe Trp Val Ala Ile 770 775 780 Leu Met Val Ile Cys Ser Leu Met Ala Leu Pro Trp Tyr Val Ala Ala 785 790 795 800 Thr Val Ile Ser Ile Ala His Ile Asp Ser Leu Lys Met Glu Thr Glu 805 810 815 Thr Ser Ala Pro Gly Glu Gln Pro Lys Phe Leu Gly Val Arg Glu Gln 820 825 830 Arg Val Thr Gly Thr Leu Val Phe Ile Leu Thr Gly Leu Ser Val Phe 835 840 845 Met Ala Pro Ile Leu Lys Phe Ile Pro Met Pro Val Leu Tyr Gly Val 850 855 860 Phe Leu Tyr Met Gly Val Ala Ser Leu Asn Gly Val Gln Phe Met Asp 865 870 875 880 Arg Leu Lys Leu Leu Leu Met Pro Leu Lys His Gln Pro Asp Phe Ile 885 890 895 Tyr Leu Arg His Val Pro Leu Arg Arg Val His Leu Phe Thr Phe Leu 900 905 910 Gln Val Leu Cys Leu Ala Leu Leu Trp Ile Leu Lys Ser Thr Val Ala 915 920 925 Ala Ile Ile Phe Pro Val Met Ile Leu Ala Leu Val Ala Val Arg Lys 930 935 940 Gly Met Asp Tyr Leu Phe Ser Gln His Asp Leu Ser Phe Leu Asp Asp 945 950 955 960 Val Ile Pro Glu Lys Asp Lys Lys Lys Lys Glu Asp Glu Lys Lys Lys 965 970 975 Lys Lys Lys Lys Gly Ser Leu Asp Ser Asp Asn Asp Asp Ser Asp Cys 980 985 990 Pro Tyr Ser Glu Lys Val Pro Ser Ile Lys Ile Pro Met Asp Ile Met 995 1000 1005 Glu Gln Gln Pro Phe Leu Ser Asp Ser Lys Pro Ser Asp Arg Glu 1010 1015 1020 Arg Ser Pro Thr Phe Leu Glu Arg His Thr Ser Cys 1025 1030 1035 <![CDATA[<210> 177]]> <![CDATA[<211> 570]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 177]]> Met Glu Ser Lys Gly Ala Ser Ser Cys Arg Leu Leu Phe Cys Leu Leu 1 5 10 15 Ile Ser Ala Thr Val Phe Arg Pro Gly Leu Gly Trp Tyr Thr Val Asn 20 25 30 Ser Ala Tyr Gly Asp Thr Ile Ile Ile Pro Cys Arg Leu Asp Val Pro 35 40 45 Gln Asn Leu Met Phe Gly Lys Trp Lys Tyr Glu Lys Pro Asp Gly Ser 50 55 60 Pro Val Phe Ile Ala Phe Arg Ser Ser Thr Lys Lys Ser Val Gln Tyr 65 70 75 80 Asp Asp Val Pro Glu Tyr Lys Asp Arg Leu Asn Leu Ser Glu Asn Tyr 85 90 95 Thr Leu Ser Ile Ser Asn Ala Arg Ile Ser Asp Glu Lys Arg Phe Val 100 105 110 Cys Met Leu Val Thr Glu Asp Asn Val Phe Glu Ala Pro Thr Ile Val 115 120 125 Lys Val Phe Lys Gln Pro Ser Lys Pro Glu Ile Val Ser Lys Ala Leu 130 135 140 Phe Leu Glu Thr Glu Gln Leu Lys Lys Leu Gly Asp Cys Ile Ser Glu 145 150 155 160 Asp Ser Tyr Pro Asp Gly Asn Ile Thr Trp Tyr Arg Asn Gly Lys Val 165 170 175 Leu His Pro Leu Glu Gly Ala Val Val Ile Ile Phe Lys Lys Glu Met 180 185 190 Asp Pro Val Thr Gln Leu Tyr Thr Met Thr Ser Thr Leu Glu Tyr Lys 195 200 205 Thr Thr Lys Ala Asp Ile Gln Met Pro Phe Thr Cys Ser Val Thr Tyr 210 215 220 Tyr Gly Pro Ser Gly Gln Lys Thr Ile His Ser Glu Gln Ala Val Phe 225 230 235 240 Asp Ile Tyr Tyr Pro Thr Glu Gln Val Thr Ile Gln Val Leu Pro Pro 245 250 255 Lys Asn Ala Ile Lys Glu Gly Asp Asn Ile Thr Leu Lys Cys Leu Gly 260 265 270 Asn Gly Asn Pro Pro Pro Glu Glu Phe Leu Phe Tyr Leu Pro Gly Gln 275 280 285 Pro Glu Gly Ile Arg Ser Ser Asn Thr Tyr Thr Leu Thr Asp Val Arg 290 295 300 Arg Asn Ala Thr Gly Asp Tyr Lys Cys Ser Leu Ile Asp Lys Lys Ser 305 310 315 320 Met Ile Ala Ser Thr Ala Ile Thr Val His Tyr Leu Asp Leu Ser Leu 325 330 335 Asn Pro Ser Gly Glu Val Thr Arg Gln Ile Gly Asp Ala Leu Pro Val 340 345 350 Ser Cys Thr Ile Ser Ala Ser Arg Asn Ala Thr Val Val Trp Met Lys 355 360 365 Asp Asn Ile Arg Leu Arg Ser Ser Pro Ser Phe Ser Ser Leu His Tyr 370 375 380 Gln Asp Ala Gly Asn Tyr Val Cys Glu Thr Ala Leu Gln Glu Val Glu 385 390 395 400 Gly Leu Lys Lys Arg Glu Ser Leu Thr Leu Ile Val Glu Gly Lys Pro 405 410 415 Gln Ile Lys Met Thr Lys Lys Thr Asp Pro Ser Gly Leu Ser Lys Thr 420 425 430 Ile Ile Cys His Val Glu Gly Phe Pro Lys Pro Ala Ile Gln Trp Thr 435 440 445 Ile Thr Gly Ser Gly Ser Val Ile Asn Gln Thr Glu Glu Ser Pro Tyr 450 455 460 Ile Asn Gly Arg Tyr Tyr Ser Lys Ile Ile Ile Ser Pro Glu Glu Asn 465 470 475 480 Val Thr Leu Thr Cys Thr Ala Glu Asn Gln Leu Glu Arg Thr Val Asn 485 490 495 Ser Leu Asn Val Ser Ala Asn Glu Asn Arg Glu Lys Val Asn Asp Gln 500 505 510 Ala Lys Leu Ile Val Gly Ile Val Val Gly Leu Leu Leu Ala Ala Leu 515 520 525 Val Ala Gly Val Val Tyr Trp Leu Tyr Met Lys Lys Ser Lys Thr Ala 530 535 540 Ser Lys His Val Asn Lys Asp Leu Gly Asn Met Glu Glu Asn Lys Lys 545 550 555 560 Leu Glu Glu Asn Asn His Lys Thr Glu Ala 565 570 <![CDATA[<210> 178]]> <![CDATA[<211> 555]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 178]]> Met Glu Ser Lys Gly Ala Ser Ser Cys Arg Leu Leu Phe Cys Leu Leu 1 5 10 15 Ile Ser Ala Thr Val Phe Arg Pro Gly Leu Gly Trp Tyr Thr Val Asn 20 25 30 Ser Ala Tyr Gly Asp Thr Ile Ile Ile Pro Cys Arg Leu Asp Val Pro 35 40 45 Gln Asn Leu Met Phe Gly Lys Trp Lys Tyr Glu Lys Pro Asp Gly Ser 50 55 60 Pro Val Phe Ile Ala Phe Arg Ser Ser Thr Lys Lys Ser Val Gln Tyr 65 70 75 80 Asp Asp Val Pro Glu Tyr Lys Asp Arg Leu Asn Leu Ser Glu Asn Tyr 85 90 95 Thr Leu Ser Ile Ser Asn Ala Arg Ile Ser Asp Glu Lys Arg Phe Val 100 105 110 Cys Met Leu Val Thr Glu Asp Asn Val Phe Glu Ala Pro Thr Ile Val 115 120 125 Lys Val Phe Lys Gln Pro Ser Lys Pro Glu Ile Val Ser Lys Ala Leu 130 135 140 Phe Leu Glu Thr Glu Gln Leu Lys Lys Leu Gly Asp Cys Ile Ser Glu 145 150 155 160 Asp Ser Tyr Pro Asp Gly Asn Ile Thr Trp Tyr Arg Asn Gly Lys Val 165 170 175 Leu His Pro Leu Glu Gly Ala Val Val Ile Ile Phe Lys Lys Glu Met 180 185 190 Asp Pro Val Thr Gln Leu Tyr Thr Met Thr Ser Thr Leu Glu Tyr Lys 195 200 205 Thr Thr Lys Ala Asp Ile Gln Met Pro Phe Thr Cys Ser Val Thr Tyr 210 215 220 Tyr Gly Pro Ser Gly Gln Lys Thr Ile His Ser Glu Gln Ala Val Phe 225 230 235 240 Asp Ile Tyr Tyr Pro Thr Glu Gln Val Thr Ile Gln Val Leu Pro Pro 245 250 255 Lys Asn Ala Ile Lys Glu Gly Asp Asn Ile Thr Leu Lys Cys Leu Gly 260 265 270 Asn Gly Asn Pro Pro Pro Glu Glu Phe Leu Phe Tyr Leu Pro Gly Gln 275 280 285 Pro Glu Gly Ile Arg Ser Ser Asn Thr Tyr Thr Leu Thr Asp Val Arg 290 295 300 Arg Asn Ala Thr Gly Asp Tyr Lys Cys Ser Leu Ile Asp Lys Lys Ser 305 310 315 320 Met Ile Ala Ser Thr Ala Ile Thr Val His Tyr Leu Asp Leu Ser Leu 325 330 335 Asn Pro Ser Gly Glu Val Thr Arg Gln Ile Gly Asp Ala Leu Pro Val 340 345 350 Ser Cys Thr Ile Ser Ala Ser Arg Asn Ala Thr Val Val Trp Met Lys 355 360 365 Asp Asn Ile Arg Leu Arg Ser Ser Pro Ser Phe Ser Ser Leu His Tyr 370 375 380 Gln Asp Ala Gly Asn Tyr Val Cys Glu Thr Ala Leu Gln Glu Val Glu 385 390 395 400 Gly Leu Lys Lys Arg Glu Ser Leu Thr Leu Ile Val Glu Gly Lys Pro 405 410 415 Gln Ile Lys Met Thr Lys Lys Thr Asp Pro Ser Gly Leu Ser Lys Thr 420 425 430 Ile Ile Cys His Val Glu Gly Phe Pro Lys Pro Ala Ile Gln Trp Thr 435 440 445 Ile Thr Gly Ser Gly Ser Val Ile Asn Gln Thr Glu Glu Ser Pro Tyr 450 455 460 Ile Asn Gly Arg Tyr Tyr Ser Lys Ile Ile Ile Ser Pro Glu Glu Asn 465 470 475 480 Val Thr Leu Thr Cys Thr Ala Glu Asn Gln Leu Glu Arg Thr Val Asn 485 490 495 Ser Leu Asn Val Ser Ala Ile Ser Ile Pro Glu His Asp Glu Ala Asp 500 505 510 Glu Ile Ser Asp Glu Asn Arg Glu Lys Val Asn Asp Gln Ala Lys Leu 515 520 525 Ile Val Gly Ile Val Val Gly Leu Leu Leu Ala Ala Leu Val Ala Gly 530 535 540 Val Val Tyr Trp Leu Tyr Met Lys Lys Ser Lys 545 550 555 <![CDATA[<210> 179]]> <![CDATA[<211> 133]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 179]]> Met Glu Ser Lys Gly Ala Ser Ser Cys Arg Leu Leu Phe Cys Leu Leu 1 5 10 15 Ile Ser Ala Thr Val Phe Arg Pro Gly Leu Gly Trp Tyr Thr Val Asn 20 25 30 Ser Ala Tyr Gly Asp Thr Ile Ile Ile Pro Cys Arg Leu Asp Val Pro 35 40 45 Gln Asn Leu Met Phe Gly Lys Trp Lys Tyr Glu Lys Pro Asp Gly Ser 50 55 60 Pro Val Phe Ile Ala Phe Arg Ser Ser Thr Lys Lys Ser Val Gln Tyr 65 70 75 80 Asp Asp Val Pro Glu Tyr Lys Asp Arg Leu Asn Leu Ser Glu Asn Tyr 85 90 95 Thr Leu Ser Ile Ser Asn Ala Arg Ile Ser Asp Glu Lys Arg Phe Val 100 105 110 Cys Met Leu Val Thr Glu Asp Asn Val Phe Glu Ala Pro Thr Ile Val 115 120 125 Lys Val Phe Ser Lys 130 <![CDATA[<210> 180]]> <![CDATA[<211> ]]>583 <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 180]]> Met Glu Ser Lys Gly Ala Ser Ser Cys Arg Leu Leu Phe Cys Leu Leu 1 5 10 15 Ile Ser Ala Thr Val Phe Arg Pro Gly Leu Gly Trp Tyr Thr Val Asn 20 25 30 Ser Ala Tyr Gly Asp Thr Ile Ile Ile Pro Cys Arg Leu Asp Val Pro 35 40 45 Gln Asn Leu Met Phe Gly Lys Trp Lys Tyr Glu Lys Pro Asp Gly Ser 50 55 60 Pro Val Phe Ile Ala Phe Arg Ser Ser Thr Lys Lys Ser Val Gln Tyr 65 70 75 80 Asp Asp Val Pro Glu Tyr Lys Asp Arg Leu Asn Leu Ser Glu Asn Tyr 85 90 95 Thr Leu Ser Ile Ser Asn Ala Arg Ile Ser Asp Glu Lys Arg Phe Val 100 105 110 Cys Met Leu Val Thr Glu Asp Asn Val Phe Glu Ala Pro Thr Ile Val 115 120 125 Lys Val Phe Lys Gln Pro Ser Lys Pro Glu Ile Val Ser Lys Ala Leu 130 135 140 Phe Leu Glu Thr Glu Gln Leu Lys Lys Leu Gly Asp Cys Ile Ser Glu 145 150 155 160 Asp Ser Tyr Pro Asp Gly Asn Ile Thr Trp Tyr Arg Asn Gly Lys Val 165 170 175 Leu His Pro Leu Glu Gly Ala Val Val Ile Ile Phe Lys Lys Glu Met 180 185 190 Asp Pro Val Thr Gln Leu Tyr Thr Met Thr Ser Thr Leu Glu Tyr Lys 195 200 205 Thr Thr Lys Ala Asp Ile Gln Met Pro Phe Thr Cys Ser Val Thr Tyr 210 215 220 Tyr Gly Pro Ser Gly Gln Lys Thr Ile His Ser Glu Gln Ala Val Phe 225 230 235 240 Asp Ile Tyr Tyr Pro Thr Glu Gln Val Thr Ile Gln Val Leu Pro Pro 245 250 255 Lys Asn Ala Ile Lys Glu Gly Asp Asn Ile Thr Leu Lys Cys Leu Gly 260 265 270 Asn Gly Asn Pro Pro Pro Glu Glu Phe Leu Phe Tyr Leu Pro Gly Gln 275 280 285 Pro Glu Gly Ile Arg Ser Ser Asn Thr Tyr Thr Leu Thr Asp Val Arg 290 295 300 Arg Asn Ala Thr Gly Asp Tyr Lys Cys Ser Leu Ile Asp Lys Lys Ser 305 310 315 320 Met Ile Ala Ser Thr Ala Ile Thr Val His Tyr Leu Asp Leu Ser Leu 325 330 335 Asn Pro Ser Gly Glu Val Thr Arg Gln Ile Gly Asp Ala Leu Pro Val 340 345 350 Ser Cys Thr Ile Ser Ala Ser Arg Asn Ala Thr Val Val Trp Met Lys 355 360 365 Asp Asn Ile Arg Leu Arg Ser Ser Pro Ser Phe Ser Ser Leu His Tyr 370 375 380 Gln Asp Ala Gly Asn Tyr Val Cys Glu Thr Ala Leu Gln Glu Val Glu 385 390 395 400 Gly Leu Lys Lys Arg Glu Ser Leu Thr Leu Ile Val Glu Gly Lys Pro 405 410 415 Gln Ile Lys Met Thr Lys Lys Thr Asp Pro Ser Gly Leu Ser Lys Thr 420 425 430 Ile Ile Cys His Val Glu Gly Phe Pro Lys Pro Ala Ile Gln Trp Thr 435 440 445 Ile Thr Gly Ser Gly Ser Val Ile Asn Gln Thr Glu Glu Ser Pro Tyr 450 455 460 Ile Asn Gly Arg Tyr Tyr Ser Lys Ile Ile Ile Ser Pro Glu Glu Asn 465 470 475 480 Val Thr Leu Thr Cys Thr Ala Glu Asn Gln Leu Glu Arg Thr Val Asn 485 490 495 Ser Leu Asn Val Ser Ala Ile Ser Ile Pro Glu His Asp Glu Ala Asp 500 505 510 Glu Ile Ser Asp Glu Asn Arg Glu Lys Val Asn Asp Gln Ala Lys Leu 515 520 525 Ile Val Gly Ile Val Val Gly Leu Leu Leu Ala Ala Leu Val Ala Gly 530 535 540 Val Val Tyr Trp Leu Tyr Met Lys Lys Ser Lys Thr Ala Ser Lys His 545 550 555 560 Val Asn Lys Asp Leu Gly Asn Met Glu Glu Asn Lys Lys Leu Glu Glu 565 570 575 Asn Asn His Lys Thr Glu Ala 580 <![CDATA[<210> 181]]> <![CDATA[<211> 757]]> <![CDATA[<212> P]]>RT <![CDATA[<213> 智人]]> <![CDATA[<400> 181]]> Met Leu Leu Arg Leu Leu Leu Ala Trp Ala Ala Ala Gly Pro Thr Leu 1 5 10 15 Gly Gln Asp Pro Trp Ala Ala Glu Pro Arg Ala Ala Cys Gly Pro Ser 20 25 30 Ser Cys Tyr Ala Leu Phe Pro Arg Arg Arg Thr Phe Leu Glu Ala Trp 35 40 45 Arg Ala Cys Arg Glu Leu Gly Gly Asp Leu Ala Thr Pro Arg Thr Pro 50 55 60 Glu Glu Ala Gln Arg Val Asp Ser Leu Val Gly Ala Gly Pro Ala Ser 65 70 75 80 Arg Leu Leu Trp Ile Gly Leu Gln Arg Gln Ala Arg Gln Cys Gln Leu 85 90 95 Gln Arg Pro Leu Arg Gly Phe Thr Trp Thr Thr Gly Asp Gln Asp Thr 100 105 110 Ala Phe Thr Asn Trp Ala Gln Pro Ala Ser Gly Gly Pro Cys Pro Ala 115 120 125 Gln Arg Cys Val Ala Leu Glu Ala Ser Gly Glu His Arg Trp Leu Glu 130 135 140 Gly Ser Cys Thr Leu Ala Val Asp Gly Tyr Leu Cys Gln Phe Gly Phe 145 150 155 160 Glu Gly Ala Cys Pro Ala Leu Gln Asp Glu Ala Gly Gln Ala Gly Pro 165 170 175 Ala Val Tyr Thr Thr Pro Phe His Leu Val Ser Thr Glu Phe Glu Trp 180 185 190 Leu Pro Phe Gly Ser Val Ala Ala Val Gln Cys Gln Ala Gly Arg Gly 195 200 205 Ala Ser Leu Leu Cys Val Lys Gln Pro Glu Gly Gly Val Gly Trp Ser 210 215 220 Arg Ala Gly Pro Leu Cys Leu Gly Thr Gly Cys Ser Pro Asp Asn Gly 225 230 235 240 Gly Cys Glu His Glu Cys Val Glu Glu Val Asp Gly His Val Ser Cys 245 250 255 Arg Cys Thr Glu Gly Phe Arg Leu Ala Ala Asp Gly Arg Ser Cys Glu 260 265 270 Asp Pro Cys Ala Gln Ala Pro Cys Glu Gln Gln Cys Glu Pro Gly Gly 275 280 285 Pro Gln Gly Tyr Ser Cys His Cys Arg Leu Gly Phe Arg Pro Ala Glu 290 295 300 Asp Asp Pro His Arg Cys Val Asp Thr Asp Glu Cys Gln Ile Ala Gly 305 310 315 320 Val Cys Gln Gln Met Cys Val Asn Tyr Val Gly Gly Phe Glu Cys Tyr 325 330 335 Cys Ser Glu Gly His Glu Leu Glu Ala Asp Gly Ile Ser Cys Ser Pro 340 345 350 Ala Gly Ala Met Gly Ala Gln Ala Ser Gln Asp Leu Gly Asp Glu Leu 355 360 365 Leu Asp Asp Gly Glu Asp Glu Glu Asp Glu Asp Glu Ala Trp Lys Ala 370 375 380 Phe Asn Gly Gly Trp Thr Glu Met Pro Gly Ile Leu Trp Met Glu Pro 385 390 395 400 Thr Gln Pro Pro Asp Phe Ala Leu Ala Tyr Arg Pro Ser Phe Pro Glu 405 410 415 Asp Arg Glu Pro Gln Ile Pro Tyr Pro Glu Pro Thr Trp Pro Pro Pro 420 425 430 Leu Ser Ala Pro Arg Val Pro Tyr His Ser Ser Val Leu Ser Val Thr 435 440 445 Arg Pro Val Val Val Ser Ala Thr His Pro Thr Leu Pro Ser Ala His 450 455 460 Gln Pro Pro Val Ile Pro Ala Thr His Pro Ala Leu Ser Arg Asp His 465 470 475 480 Gln Ile Pro Val Ile Ala Ala Asn Tyr Pro Asp Leu Pro Ser Ala Tyr 485 490 495 Gln Pro Gly Ile Leu Ser Val Ser His Ser Ala Gln Pro Pro Ala His 500 505 510 Gln Pro Pro Met Ile Ser Thr Lys Tyr Pro Glu Leu Phe Pro Ala His 515 520 525 Gln Ser Pro Met Phe Pro Asp Thr Arg Val Ala Gly Thr Gln Thr Thr 530 535 540 Thr His Leu Pro Gly Ile Pro Pro Asn His Ala Pro Leu Val Thr Thr 545 550 555 560 Leu Gly Ala Gln Leu Pro Pro Gln Ala Pro Asp Ala Leu Val Leu Arg 565 570 575 Thr Gln Ala Thr Gln Leu Pro Ile Ile Pro Thr Ala Gln Pro Ser Leu 580 585 590 Thr Thr Thr Ser Arg Ser Pro Val Ser Pro Ala His Gln Ile Ser Val 595 600 605 Pro Ala Ala Thr Gln Pro Ala Ala Leu Pro Thr Leu Leu Pro Ser Gln 610 615 620 Ser Pro Thr Asn Gln Thr Ser Pro Ile Ser Pro Thr His Pro His Ser 625 630 635 640 Lys Ala Pro Gln Ile Pro Arg Glu Asp Gly Pro Ser Pro Lys Leu Ala 645 650 655 Leu Trp Leu Pro Ser Pro Ala Pro Thr Ala Ala Pro Thr Ala Leu Gly 660 665 670 Glu Ala Gly Leu Ala Glu His Ser Gln Arg Asp Asp Arg Trp Leu Leu 675 680 685 Val Ala Leu Leu Val Pro Thr Cys Val Phe Leu Val Val Leu Leu Ala 690 695 700 Leu Gly Ile Val Tyr Cys Thr Arg Cys Gly Pro His Ala Pro Asn Lys 705 710 715 720 Arg Ile Thr Asp Cys Tyr Arg Trp Val Ile His Ala Gly Ser Lys Ser 725 730 735 Pro Thr Glu Pro Met Pro Pro Arg Gly Ser Leu Thr Gly Val Gln Thr 740 745 750 Cys Arg Thr Ser Val 755 <![CDATA[<210> 182]]> <![CDATA[<211> 21]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 182]]> Gly Ser Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu 1 5 10 15 Glu Asn Pro Gly Pro 20 <![CDATA[<210> 183]]> <![CDATA[<211> 22]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 183]]> Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val 1 5 10 15 Glu Glu Asn Pro Gly Pro 20 <![CDATA[<210> 184]]> <![CDATA[<211> 23]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 184]]> Gly Ser Gly Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp 1 5 10 15 Val Glu Ser Asn Pro Gly Pro 20 <![CDATA[<210> 185]]> <![CDATA[<211> 25]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 185]]> Gly Ser Gly Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala 1 5 10 15 Gly Asp Val Glu Ser Asn Pro Gly Pro 20 25
Claims (224)
- 一種用於產生角膜內皮細胞之方法,該方法包含增加角膜內皮祖細胞中之至少一種選自由PITX2、FOXC1、TFAP2B、LMX1B及POU6F2組成之群之轉錄因子之表現,藉此產生角膜內皮細胞。
- 如請求項1之方法,其中該等角膜內皮細胞為成熟角膜內皮細胞。
- 如請求項1或2之方法,其中該轉錄因子為PITX2。
- 如請求項1至3中任一項之方法,其中PITX2為至少一種選自由以下組成之群之PITX2之同功型:PITX2,同功型1;PITX2,同功型2;PITX2,同功型3;PITX2,同功型4;及PITX2,同功型5。
- 如請求項1或2之方法,其中該轉錄因子為FOXC1。
- 如請求項1或2之方法,其中該轉錄因子為TFAP2B。
- 如請求項1、2或6中任一項之方法,其中TFAP2B為至少一種選自由以下組成之群之TFAP2B之同功型:TFAP2B,同功型1;及TFAP2B,同功型2。
- 如請求項1或2之方法,其中該轉錄因子為LMX1B。
- 如請求項1、2或8中任一項之方法,其中LMX1B為至少一種選自由以下組成之群之LMX1B之同功型:LMX1B,同功型1;LMX1B,同功型2;及LMX1B,同功型3。
- 如請求項1或2之方法,其中該轉錄因子為POU6F2。
- 如請求項1、2或9中任一項之方法,其中POU6F2為至少一種選自由以下組成之群之POU6F2之同功型:POU6F2,同功型1;及POU6F2,同功型2。
- 如請求項1至11中任一項之方法,其進一步包含增加角膜內皮祖細胞中之一或多種選自由以下組成之群之轉錄因子之表現:ATF4、ATMIN、BHLHE40、CEBPD、CSRNP1、DRAP1、EGR1、ELF2、EMX2、ESRRA、ETS2、FOS、FOSB、FOSL2、GTF3A、HIF1A、JUN、JUN B、JUN D、KLF10、KLF9、MBD3、NFE2L1、NME2、NR1D1、NR4A1、PA2G4、POU3F3、RELA、TBX2、TFDP1、TSC22D1、USF2、YBX1、ZNF207、ZNF358及ZNF395。
- 如請求項1至12中任一項之方法,其中增加該等角膜內皮祖細胞中之該至少一種轉錄因子之表現包含使該等角膜內皮祖細胞與該至少一種轉錄因子接觸。
- 如請求項1至13中任一項之方法,其中該等角膜內皮祖細胞包含表現載體,其包含編碼該至少一種轉錄因子之核酸。
- 如請求項14之方法,其中該表現載體為病毒載體。
- 如請求項14之方法,其中該表現載體為非病毒載體。
- 如請求項14之方法,其中該表現載體為誘導型表現載體。
- 如請求項14至17中任一項之方法,其中該表現載體包含以可操作方式連接至編碼該至少一種轉錄因子之核酸之啟動子。
- 如請求項18之方法,其中該啟動子為內源性啟動子。
- 如請求項18之方法,其中該啟動子為人工啟動子。
- 如請求項18至20中任一項之方法,其中該啟動子為誘導型啟動子。
- 如請求項1至14中任一項之方法,其中增加該等角膜內皮祖細胞中之該至少一種轉錄因子之表現包含用編碼該至少一種轉錄因子之病毒載體轉導角膜內皮祖細胞。
- 如請求項1至14中任一項之方法,其中增加該等角膜內皮祖細胞中之該至少一種轉錄因子之表現包含用編碼該至少一種轉錄因子之表現載體轉染角膜內皮祖細胞。
- 如請求項1至23中任一項之方法,其中在增加該至少一種轉錄因子之表現之前,由該等角膜內皮祖細胞培養至少2、3、4、5、6、7、8、9、10、11或12天。
- 如請求項1至24中任一項之方法,其中在增加該至少一種轉錄因子之表現之後,由該等角膜內皮祖細胞培養至少10、12、14、16、18、20、21、22、23、24、25、26、27、28、29或30天。
- 如請求項1至4或12至25中任一項之方法,其中增加該PITX2之表現包含相對於該等角膜內皮祖細胞中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1,000倍或10,000倍。
- 如請求項1、2、5或12至25中任一項之方法,其中增加該FOXC1之表現包含相對於該等角膜內皮祖細胞中之FOXC1之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項1、2、6、7或12至25中任一項之方法,其中增加該TFAP2B之表現包含相對於該等角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項1、2、8、9或12至25中任一項之方法,其中增加該LMX1B之表現包含相對於該等角膜內皮祖細胞中之LMX1B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項1、2、10、11或12至25中任一項之方法,其中增加該POU6F2之表現包含相對於該等角膜內皮祖細胞中之POU6F2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項1至30中任一項之方法,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現增加之一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B、LMX1B及MRGPRX3。
- 如請求項1至31中任一項之方法,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現增加之一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B及LMX1B。
- 如請求項1至32中任一項之方法,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現增加之一或多種選自由以下組成之群之標記物之表現:COL8A1、COL8A2、SLC4A11及MRGPRX3。
- 如請求項31至33中任一項之方法,其中該增加之一或多種標記物之表現包含相對於角膜內皮祖細胞增加至少2倍、5倍、10倍、50倍、100倍、200倍、500倍、1,000倍、2,000倍、5,000倍或10,000倍。
- 如請求項1至34中任一項之方法,其中該角膜內皮細胞相對於角膜內皮祖細胞,呈現降低之NGFR、SOX10、HNK1、SSEA4、NANOG、OCT4、vWF及/或CD31之表現。
- 如請求項35之方法,其中該降低之NGFR、SOX10、HNK1、SSEA4、NANOG、OCT4、vWF及/或CD31之表現包含相對於角膜內皮祖細胞降低至少0.1倍、0.2倍、0.5倍、1倍、2倍、3倍或4倍。
- 如請求項1至36中任一項之方法,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現以下中之一或多者:增加之泵送功能、增強之緊密接合區形成、增加之對氧化應力之抗性及增加之多邊形形態。
- 如請求項37之方法,其中該增加之泵送功能、增強之緊密接合區形成、增加之對氧化應力之抗性及增加之多邊形形態包含相對於角膜內皮祖細胞增加至少5%、10%、15%、20%或25%。
- 如請求項1至38中任一項之方法,其中增加該至少一種轉錄因子之表現,使角膜內皮祖細胞之總轉錄本朝向角膜內皮細胞之總轉錄本偏移至少1%、5%、10%、20%、30%、40%或50%。
- 如請求項1至39中任一項之方法,其中該等角膜內皮祖細胞係衍生自富潛能幹細胞。
- 如請求項40之方法,其中該等富潛能幹細胞為胚胎幹細胞或誘導性富潛能幹細胞。
- 如請求項1至41中任一項之方法,其中誘導該等角膜內皮祖細胞中之該至少一種轉錄因子之表現包含使用編碼該至少一種轉錄因子之基因開關構築體。
- 如請求項42之方法,其中該基因開關構築體為轉錄基因開關構築體。
- 如請求項43之方法,其中該基因開關構築體為轉錄後基因開關構築體。
- 一種產生富潛能幹細胞衍生之角膜內皮細胞之方法,該方法包含: (a) 培養富潛能幹細胞及誘導角膜內皮祖細胞之形成,其中該等富潛能幹細胞包含表現載體,該表現載體包含編碼至少一種選自由以下組成之群之轉錄因子之核酸:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2,及 (b) 增加該等角膜內皮祖細胞中來自該表現載體之該至少一種轉錄因子之表現,藉此產生角膜內皮細胞。
- 如請求項45之方法,其中該角膜內皮細胞為成熟角膜內皮細胞。
- 如請求項45之方法,其中該等富潛能幹細胞為胚胎幹細胞。
- 如請求項45之方法,其中該等富潛能幹細胞為誘導性富潛能幹細胞。
- 如請求項45或46之方法,其中該轉錄因子為PITX2。
- 如請求項45、46或49中任一項之方法,其中該PITX2為至少一種選自由以下組成之群之PITX2之同功型:PITX2,同功型1;PITX2,同功型2;PITX2,同功型3;PITX2,同功型4;及PITX2,同功型5。
- 如請求項45或46之方法,其中該轉錄因子為FOXC1。
- 如請求項45或46之方法,其中該轉錄因子為TFAP2B。
- 如請求項45、46或52中任一項之方法,其中TFAP2B為至少一種選自由以下組成之群之TFAP2B之同功型:TFAP2B,同功型1;及TFAP2B,同功型2。
- 如請求項45或46之方法,其中該轉錄因子為LMX1B。
- 如請求項45、46或54中任一項之方法,其中LMX1B為至少一種選自由以下組成之群之LMX1B之同功型:LMX1B,同功型1;LMX1B,同功型2;及LMX1B,同功型3。
- 如請求項45或46之方法,其中該轉錄因子為POU6F2。
- 如請求項45、46或56中任一項之方法,其中POU6F2為至少一種選自由以下組成之群之POU6F2之同功型:POU6F2,同功型1;及POU6F2,同功型2。
- 如請求項45至57中任一項之方法,其進一步包含增加一或多種選自由以下組成之群之轉錄因子之表現:ERG、ATF4、ATMIN、BHLHE40、CEBPD、CSRNP1、DRAP1、EGR1、ELF2、EMX2、ESRRA、ETS2、FOS、FOSB、FOSL2、GTF3A、HIF1A、JUN、JUNB、JUND、KLF10、KLF9、MBD3、NFE2L1、NME2、NR1D1、NR4A1、PA2G4、POU3F3、RELA、TBX2、TFDP1、TSC22D1、USF2、YBX1、ZNF207、ZNF358及ZNF395。
- 如請求項45至48中任一項之方法,其中該表現載體為病毒載體。
- 如請求項45至48中任一項之方法,其中該表現載體為非病毒載體。
- 如請求項45至60中任一項之方法,其中該表現載體為誘導型表現載體。
- 如請求項45至61中任一項之方法,其中該表現載體包含以可操作方式連接至編碼該至少一種轉錄因子之核酸之啟動子。
- 如請求項62之方法,其中該啟動子為內源性啟動子。
- 如請求項62之方法,其中該啟動子為人工啟動子。
- 如請求項62至64中任一項之方法,其中該啟動子為誘導型啟動子。
- 如請求項45至65中任一項之方法,其中增加該等角膜內皮祖細胞中該至少一種轉錄因子之表現包含誘導該等角膜內皮祖細胞中該至少一種轉錄因子之表現。
- 如請求項66之方法,其中誘導該等角膜內皮祖細胞中該至少一種轉錄因子之表現包含使用編碼該至少一種轉錄因子之基因開關構築體。
- 如請求項67之方法,其中該基因開關構築體為轉錄基因開關構築體。
- 如請求項67之方法,其中該基因開關構築體為轉錄後基因開關構築體。
- 如請求項45至59及61至69中任一項之方法,其中用編碼該至少一種轉錄因子之病毒載體轉導該等富潛能幹細胞。
- 如請求項45至58及60至69中任一項之方法,其中用編碼該至少一種轉錄因子之表現載體轉染該等富潛能幹細胞。
- 如請求項45之方法,其中步驟(a)包含由該等富潛能幹細胞與小型/母體抗果蠅皮膚生長因子(Small/Mothers Against Decapentaplegic;SMAD)蛋白質信號傳導之至少一種抑制劑一起培養,以誘導該等富潛能幹細胞分化成角膜內皮祖細胞。
- 如請求項42至68中任一項之方法,其中在增加該至少一種轉錄因子之表現之前,將該等角膜內皮祖細胞培養至少2、3、4、5、6、7、8、9、10、11或12天。
- 如請求項45至72中任一項之方法,其中在增加該至少一種轉錄因子之表現之後,將該等角膜內皮祖細胞培養至少8、10、12、14、16、18、20、21、22、23、24、25、26、27、28、29或30天。
- 如請求項45至50及58至74中任一項之方法,其中增加該PITX2之表現包含相對於該等角膜內皮祖細胞中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項45至48、51及58至74中任一項之方法,其中增加該FOXC1之表現包含相對於該等角膜內皮祖細胞中之FOXC1之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項45至48、52、53及58至74中任一項之方法,其中增加該TFAP2B之表現包含相對於該等角膜內皮祖細胞中之TFAP2B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項45至48、54至55及58至74中任一項之方法,其中增加該LMX1B之表現包含相對於該等角膜內皮祖細胞中之LMX1B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項45至48及56至74中任一項之方法,其中增加該POU6F2之表現包含相對於該等角膜內皮祖細胞中之POU6F2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項45至79中任一項之方法,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現增加一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B、LMX1B及MRGPRX3。
- 如請求項45至80中任一項之方法,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現增加一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B及LMX1B。
- 如請求項45至81中任一項之方法,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現增加一或多種選自由以下組成之群之標記物之表現:COL8A1、COL8A2、SLC4A11及MRGPRX3。
- 如請求項80至82中任一項之方法,其中該增加之一或多種標記物之表現包含相對於角膜內皮祖細胞增加至少2倍、5倍、10倍、50倍、100倍、200倍、500倍、1,000倍、2,000倍、5,000倍或10,000倍。
- 如請求項45至83中任一項之方法,其中該角膜內皮細胞相對於角膜內皮祖細胞呈現降低之NGFR、SOX10、HNK1、SSEA4、NANOG、OCT4、vWF及/或CD31之表現。
- 如請求項84之方法,其中該降低之NGFR、SOX10、HNK1、SSEA4、NANOG、OCT4、vWF及/或CD31之表現包含相對於角膜內皮祖細胞降低至少0.1倍、0.2倍、0.5倍、1倍、2倍、3倍或4倍。
- 如請求項45至85中任一項之方法,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現以下中之一或多者:增加之泵送功能、增強之緊密接合區形成、增加對氧化應力之抗性、及增加之多邊形形態。
- 如請求項86之方法,其中該增加之泵送功能、增強之緊密接合區形成、增加對氧化應力之抗性、及增加之多邊形形態包含相對於角膜內皮祖細胞增加至少5%、10%、15%、20%或25%。
- 如請求項45至87中任一項之方法,其中增加該至少一種轉錄因子之表現,使角膜內皮祖細胞之總轉錄本朝向角膜內皮細胞之總轉錄本偏移至少1%、5%、10%、20%、30%、40%或50%。
- 一種角膜內皮細胞群體,其係藉由如請求項45至88中任一項之方法產生。
- 一種醫藥組合物,其包含藉由如請求項1至89中任一項之方法產生之角膜內皮細胞群體,及醫藥學上可接受之載劑。
- 一種角膜內皮細胞群體,其包含相對於該角膜內皮細胞群體中之轉錄因子之內源性表現量增加至少一種選自由以下組成之群之轉錄因子之表現量;PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
- 如請求項91之角膜內皮細胞群體,其中該等角膜內皮細胞為成熟角膜內皮細胞。
- 如請求項91或92之角膜內皮細胞群體,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現增加一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B、LMX1B及MRGPRX3。
- 如請求項91至93中任一項之角膜內皮細胞群體,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現增加一或多種選自由以下組成之群之標記物之表現:PITX2、SLC4A11、FOXC1、COL8A1、COL8A2、TFAP2B及LMX1B。
- 如請求項91至94中任一項之角膜內皮細胞群體,其中該等角膜內皮細胞相對於角膜內皮祖細胞呈現增加一或多種選自由以下組成之群之標記物之表現:COL8A1、COL8A2、SLC4A11及MRGPRX3。
- 如請求項91至95中任一項之角膜內皮細胞群體,其中該增加之表現包含該至少一種轉錄因子之外源性表現。
- 如請求項91至96中任一項之角膜內皮細胞群體,其中該等角膜內皮細胞包含表現載體,其包含編碼該至少一種轉錄因子之核酸。
- 如請求項97之角膜內皮細胞群體,其中該表現載體為病毒載體。
- 如請求項98之角膜內皮細胞群體,其中該病毒載體係選自由以下組成之群:腺相關病毒(AAV)載體、腺病毒載體、慢病毒載體、單純疱疹病毒載體、仙台病毒(sendai virus)載體及反轉錄病毒載體。
- 如請求項97之角膜內皮細胞群體,其中該表現載體為非病毒載體。
- 如請求項100之角膜內皮細胞群體,其中該非病毒載體係選自由以下組成之群:質體DNA、線性雙股DNA (dsDNA)、線性單股DNA (ssDNA)、奈米質體、微型環DNA、單股寡脫氧核苷酸(ssODN)、DDNA寡核苷酸、單股mRNA (ssRNA)、及雙股mRNA (dsRNA)。
- 如請求項100至101中任一項之角膜內皮細胞群體,其中該非病毒載體包含裸核酸、脂質體、樹枝狀聚合物、奈米粒子、脂質-聚合物系統、固體脂質奈米粒子、及/或脂質體魚精蛋白/DNA脂質複合物(LPD)。
- 如請求項97之角膜內皮細胞群體,其中該表現載體為誘導型表現載體。
- 如請求項97至103中任一項之角膜內皮細胞群體,其中該表現載體包含以可操作方式連接至編碼該至少一種轉錄因子之核酸之啟動子。
- 如請求項104之角膜內皮細胞群體,其中該啟動子為內源性啟動子。
- 如請求項104之角膜內皮細胞群體,其中該啟動子為人工啟動子。
- 如請求項104至106中任一項之角膜內皮細胞群體,其中該啟動子為誘導型啟動子。
- 如請求項91至107中任一項之角膜內皮細胞群體,其中該轉錄因子為PITX2。
- 如請求項108之角膜內皮細胞群體,其中該增加之PITX2之表現包含相對於該角膜內皮細胞群體中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項91至107中任一項之角膜內皮細胞群體,其中該轉錄因子為FOXC1。
- 如請求項110之角膜內皮細胞群體,其中該增加之FOXC1之表現包含相對於該角膜內皮細胞群體中之FOXC1之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項91至107中任一項之角膜內皮細胞群體,其中該轉錄因子為TFAP2B。
- 如請求項112之角膜內皮細胞群體,其中該增加之TFAP2B之表現包含相對於該角膜內皮細胞群體中之TFAP2B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項91至107中任一項之角膜內皮細胞群體,其中該轉錄因子為LMX1B。
- 如請求項114之角膜內皮細胞群體,其中該增加之LMX1B之表現包含相對於該角膜內皮細胞群體中之LMX1B之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項91至107中任一項之角膜內皮細胞群體,其中該轉錄因子為POU6F2。
- 如請求項116之角膜內皮細胞群體,其中該增加之POU6F2之表現包含相對於該角膜內皮細胞群體中之PITX2之內源性表現量增加至少0.1倍、0.2倍、0.5倍、1倍、2倍、5倍、10倍、20倍、50倍、100倍、200倍、500倍、1000倍或10,000倍。
- 如請求項91至117中任一項之角膜內皮細胞群體,其中該角膜內皮細胞群體為成熟角膜內皮細胞群體。
- 如請求項91至117中任一項之角膜內皮細胞群體,其中該等角膜內皮細胞係衍生自富潛能幹細胞。
- 如請求項119之角膜內皮細胞群體,其中該等富潛能幹細胞為胚胎幹細胞或誘導性富潛能幹細胞。
- 如請求項91至120中任一項之角膜內皮細胞群體,其中該角膜內皮細胞群體包含至少10 6個角膜內皮細胞。
- 一種富潛能幹細胞,其包含表現載體,該表現載體包含編碼至少一種選自由以下組成之群之轉錄因子之核酸:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
- 如請求項122之富潛能幹細胞,其中該表現載體為病毒載體。
- 如請求項122之富潛能幹細胞,其中該表現載體為非病毒載體。
- 如請求項122之富潛能幹細胞,其中該表現載體為誘導型表現載體。
- 如請求項122至125中任一項之富潛能幹細胞,其中該表現載體包含以可操作方式連接至編碼該至少一種轉錄因子之核酸之啟動子。
- 如請求項126之富潛能幹細胞,其中該啟動子為內源性啟動子。
- 如請求項126之富潛能幹細胞,其中該啟動子為人工啟動子。
- 如請求項126至128中任一項之富潛能幹細胞,其中該啟動子為誘導型啟動子。
- 如請求項122至129中任一項之富潛能幹細胞,其中該等富潛能幹細胞包含編碼該至少一種轉錄因子之基因開關構築體。
- 如請求項130之富潛能幹細胞,其中該基因開關構築體為轉錄基因開關構築體。
- 如請求項130之富潛能幹細胞,其中該基因開關構築體為轉錄後基因開關構築體。
- 一種角膜內皮細胞,其包含表現載體,該表現載體包含編碼至少一種選自由以下組成之群之轉錄因子之核酸:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
- 如請求項133之角膜內皮細胞,其中該角膜內皮細胞為成熟角膜內皮細胞。
- 如請求項133或134中任一項之角膜內皮細胞,其中該表現載體為病毒載體。
- 如請求項133或134中任一項之角膜內皮細胞,其中該表現載體為非病毒載體。
- 如請求項133或134中任一項之角膜內皮細胞,其中該表現載體為誘導型表現載體。
- 如請求項133至137中任一項之角膜內皮細胞,其中該表現載體包含以可操作方式連接至編碼該至少一種轉錄因子之核酸之啟動子。
- 如請求項138之角膜內皮細胞,其中該啟動子為內源性啟動子。
- 如請求項138之角膜內皮細胞,其中該啟動子為人工啟動子。
- 如請求項138至140中任一項之角膜內皮細胞,其中該啟動子為誘導型啟動子。
- 如請求項133至141中任一項之角膜內皮細胞,其中該等富潛能幹細胞包含編碼該至少一種轉錄因子之基因開關構築體。
- 如請求項142之角膜內皮細胞,其中該基因開關構築體為轉錄基因開關構築體。
- 如請求項142之角膜內皮細胞,其中該基因開關構築體為轉錄後基因開關構築體。
- 一種醫藥組合物,其包含如請求項89之角膜內皮細胞群體、如請求項91至121中任一項之角膜內皮細胞群體、或如請求項133至144中任一項之角膜內皮細胞,及醫藥學上可接受之載劑。
- 一種治療有需要之個體中之疾病之方法,該方法包含向該個體投與有效量之如請求項89之角膜內皮細胞群體、如請求項91至121中任一項之角膜內皮細胞群體、如請求項133至144中任一項之角膜內皮細胞、或如請求項145之醫藥組合物,藉此治療該個體中之疾病。
- 如請求項144之方法,其中該疾病係選自由以下組成之群:法曲氏營養不良(Fuch's dystrophy)、虹膜角膜內皮症候群、後部多形性營養不良、先天性遺傳性內皮營養不良、角膜營養不良、及角膜移植中之晚期內皮衰竭。
- 一種治療有需要之個體之方法,其中該個體呈現引起大皰性角膜病變之角膜水腫之症狀,其中該個體患有由使用隱形眼鏡或白內障手術引起之眼部損傷或其中該個體患有持續性手術創傷,該方法包含向該個體投與有效量之如請求項89之成熟角膜內皮細胞群體、如請求項92至121中任一項之角膜內皮細胞群體、如請求項133至144中任一項之角膜內皮細胞、或如請求項145之醫藥組合物,藉此治療該個體。
- 一種套組,其包含如請求項89之成熟角膜內皮細胞群體、如請求項91至121中任一項之角膜內皮細胞群體、如請求項133至144中任一項之角膜內皮細胞、或如請求項145之醫藥組合物。
- 一種套組,其包含表現載體,該表現載體包含編碼至少一種選自由以下組成之群之轉錄因子之核酸:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
- 一種套組,其包含至少一種選自由以下組成之群之轉錄因子:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2。
- 如請求項14之方法,其中該表現載體包含自我裂解序列。
- 如請求項45之方法,其中該表現載體包含自我裂解序列。
- 一種產生富潛能幹細胞衍生之角膜內皮細胞之方法,該方法包含: (a) 培養富潛能幹細胞及誘導形成神經脊幹細胞,其中該等富潛能幹細胞包含表現載體,該表現載體包含編碼至少一種選自由以下組成之群之轉錄因子之核酸:PITX2、FOXC1、TFAP2B、LMX1B及POU6F2,及 (b) 增加神經脊幹細胞中來自該表現載體之至少一種轉錄因子之表現,藉此產生角膜內皮細胞。
- 如請求項1之方法,其中PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項1之方法,其中FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項1之方法,其中TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項1之方法,其中LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項1之方法,其中POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項150之套組,其中PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項150之套組,其中FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項150之套組,其中TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項150之套組,其中LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 請求項150之套組,其中POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中PITX2包含與由SEQ ID NO:1至SEQ ID NO:6之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中FOXC1包含與由SEQ ID NO:7之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中TFAP2B包含與由SEQ ID NO:8之核苷酸序列編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中LMX1B包含與由SEQ ID NO:9至SEQ ID NO:11之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中POU6F2包含與由SEQ ID NO:12至SEQ ID NO:13之核苷酸序列中之任一者編碼的胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項1之方法,其中PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項1之方法,其中FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項1之方法,其中TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項1之方法,其中LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項1之方法,其中POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項45之方法,其中POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中PITX2包含與SEQ ID NO:51至SEQ ID NO:52中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項91之群體,其中POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項122之富潛能幹細胞,其中POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項133之角膜內皮細胞,其中POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項150之套組,其中PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項150之套組,其中FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項150之套組,其中TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項150之套組,其中LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項150之套組,其中POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中PITX2包含與SEQ ID NO:51至SEQ ID NO:53中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中FOXC1包含與SEQ ID NO:54中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中TFAP2B包含與SEQ ID NO:55中所闡述之胺基酸序列至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中LMX1B包含與SEQ ID NO:56至SEQ ID NO:58中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
- 如請求項154之方法,其中POU6F2包含與SEQ ID NO:59至SEQ ID NO:60中所闡述之胺基酸序列中之任一者至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%一致之胺基酸序列。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202163183562P | 2021-05-03 | 2021-05-03 | |
US63/183,562 | 2021-05-03 |
Publications (1)
Publication Number | Publication Date |
---|---|
TW202309274A true TW202309274A (zh) | 2023-03-01 |
Family
ID=81750591
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW111116689A TW202309274A (zh) | 2021-05-03 | 2022-05-03 | 產生成熟角膜內皮細胞之方法 |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP4334437A1 (zh) |
JP (1) | JP2024519218A (zh) |
KR (1) | KR20240005837A (zh) |
CN (1) | CN117242173A (zh) |
AU (1) | AU2022270611A1 (zh) |
BR (1) | BR112023021993A2 (zh) |
CA (1) | CA3216719A1 (zh) |
TW (1) | TW202309274A (zh) |
WO (1) | WO2022235586A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024092086A1 (en) * | 2022-10-26 | 2024-05-02 | The Trustees Of The University Of Pennsylvania | Compositions and methods for regenerating corneal endothelium |
Family Cites Families (108)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3421217A (en) | 1967-06-29 | 1969-01-14 | Schick Electric Inc | Hair receptacle for electric shaver |
US5166048A (en) | 1981-03-02 | 1992-11-24 | Soll David B | Protection of human corneal endothelial cells |
US4678783B1 (en) | 1983-11-04 | 1995-04-04 | Asahi Chemical Ind | Substituted isoquinolinesulfonyl compounds |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4959319A (en) | 1985-08-01 | 1990-09-25 | Skelnik Debra L | Process of corneal enhancement |
US5269812A (en) | 1986-05-16 | 1993-12-14 | White Thomas C | Methods and devices employed in replacement of the corneal endothelium |
GB2197915B (en) | 1986-11-19 | 1990-11-14 | Rolls Royce Plc | Improvements in or relating to fluid bearings |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5302523A (en) | 1989-06-21 | 1994-04-12 | Zeneca Limited | Transformation of plant cells |
US5550318A (en) | 1990-04-17 | 1996-08-27 | Dekalb Genetics Corporation | Methods and compositions for the production of stably transformed, fertile monocot plants and cells thereof |
US7705215B1 (en) | 1990-04-17 | 2010-04-27 | Dekalb Genetics Corporation | Methods and compositions for the production of stably transformed, fertile monocot plants and cells thereof |
US5322783A (en) | 1989-10-17 | 1994-06-21 | Pioneer Hi-Bred International, Inc. | Soybean transformation by microparticle bombardment |
US5484956A (en) | 1990-01-22 | 1996-01-16 | Dekalb Genetics Corporation | Fertile transgenic Zea mays plant comprising heterologous DNA encoding Bacillus thuringiensis endotoxin |
AU8532691A (en) | 1990-08-01 | 1992-03-02 | Chiron Ophthalmics Inc. | Method for treating corneal endothelial wounds |
CA2093664C (en) | 1990-10-12 | 2003-07-29 | Fritz Eckstein | Modified ribozymes |
US5486359A (en) | 1990-11-16 | 1996-01-23 | Osiris Therapeutics, Inc. | Human mesenchymal stem cells |
US5384253A (en) | 1990-12-28 | 1995-01-24 | Dekalb Genetics Corporation | Genetic transformation of maize cells by electroporation of cells pretreated with pectin degrading enzymes |
WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
US5610042A (en) | 1991-10-07 | 1997-03-11 | Ciba-Geigy Corporation | Methods for stable transformation of wheat |
US5652094A (en) | 1992-01-31 | 1997-07-29 | University Of Montreal | Nucleozymes |
ATE398679T1 (de) | 1992-07-07 | 2008-07-15 | Japan Tobacco Inc | Verfahren zur transformation einer monokotyledon pflanze |
US5702932A (en) | 1992-07-20 | 1997-12-30 | University Of Florida | Microinjection methods to transform arthropods with exogenous DNA |
WO1994002620A2 (en) | 1992-07-27 | 1994-02-03 | Pioneer Hi-Bred International, Inc. | An improved method of agrobacterium-mediated transformation of cultured soybean cells |
DE4228457A1 (de) | 1992-08-27 | 1994-04-28 | Beiersdorf Ag | Herstellung von heterodimerem PDGF-AB mit Hilfe eines bicistronischen Vektorsystems in Säugerzellen |
US5589451A (en) | 1992-09-21 | 1996-12-31 | Board Of Regents, The University Of Texas System | Methods and treaments for corneal healing with hepatocyte and keratinocyte growth factors |
US5703047A (en) | 1992-09-21 | 1997-12-30 | Board Of Regents, The University Of Texas System | Methods and treatments for corneal healing with growth factors |
GB9222888D0 (en) | 1992-10-30 | 1992-12-16 | British Tech Group | Tomography |
US5656610A (en) | 1994-06-21 | 1997-08-12 | University Of Southern California | Producing a protein in a mammal by injection of a DNA-sequence into the tongue |
FR2722208B1 (fr) | 1994-07-05 | 1996-10-04 | Inst Nat Sante Rech Med | Nouveau site interne d'entree des ribosomes, vecteur le contenant et utilisation therapeutique |
US5584881A (en) | 1994-08-12 | 1996-12-17 | Rowsey; J. James | Sutureless corneal transplantation apparatus and method |
US5649944A (en) | 1994-08-12 | 1997-07-22 | Collins; Joseph Patrick | Apparatus for preparing cornea material for tabbed (sutureless) transplantation |
US5755785A (en) | 1994-08-12 | 1998-05-26 | The University Of South Florida | Sutureless corneal transplantation method |
US5736524A (en) | 1994-11-14 | 1998-04-07 | Merck & Co.,. Inc. | Polynucleotide tuberculosis vaccine |
US5843780A (en) | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
US7410773B2 (en) | 1995-02-02 | 2008-08-12 | Ghazi Jaswinder Dhoot | Method of preparing an undifferentiated cell |
US5908782A (en) | 1995-06-05 | 1999-06-01 | Osiris Therapeutics, Inc. | Chemically defined medium for human mesenchymal stem cells |
US5780448A (en) | 1995-11-07 | 1998-07-14 | Ottawa Civic Hospital Loeb Research | DNA-based vaccination of fish |
US5686414A (en) | 1995-11-14 | 1997-11-11 | Xoma Corporation | Methods of treating conditions associated with corneal transplantation |
US5928906A (en) | 1996-05-09 | 1999-07-27 | Sequenom, Inc. | Process for direct sequencing during template amplification |
US5945100A (en) | 1996-07-31 | 1999-08-31 | Fbp Corporation | Tumor delivery vehicles |
EP0931158A1 (en) | 1996-09-06 | 1999-07-28 | The Trustees Of The University Of Pennsylvania | An inducible method for production of recombinant adeno-associated viruses utilizing t7 polymerase |
US5981274A (en) | 1996-09-18 | 1999-11-09 | Tyrrell; D. Lorne J. | Recombinant hepatitis virus vectors |
EP1005486A4 (en) | 1997-08-22 | 2004-09-29 | Univ Washington | INDUCTIBLE REGULATOR SYSTEM AND USE THEREOF |
US5994624A (en) | 1997-10-20 | 1999-11-30 | Cotton Incorporated | In planta method for the production of transgenic plants |
JP4316794B2 (ja) | 1997-10-22 | 2009-08-19 | 株式会社デ・ウエスタン・セラピテクス研究所 | イソキノリン誘導体及び医薬 |
US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
DE69931051D1 (de) | 1998-05-25 | 2006-06-01 | Santen Pharmaceutical Co Ltd | Neue vinylbenzolderivate |
US7410798B2 (en) | 2001-01-10 | 2008-08-12 | Geron Corporation | Culture system for rapid expansion of human embryonic stem cells |
DK1975243T3 (da) | 1998-12-07 | 2010-06-28 | Univ Duke | BODIPY-aminoacetaldehyddiethylacetal |
AUPQ147799A0 (en) | 1999-07-07 | 1999-07-29 | Medvet Science Pty. Ltd. | Mesenchymal precursor cell |
US7015037B1 (en) | 1999-08-05 | 2006-03-21 | Regents Of The University Of Minnesota | Multiponent adult stem cells and methods for isolation |
JP2004501664A (ja) | 2000-06-30 | 2004-01-22 | ボード・オブ・リージェンツ,ザ・ユニヴァーシティ・オヴ・テキサス・システム | 標的化薬剤送達のための腫瘍組織を浸潤する細胞特異的な内部移行ペプチドの単離 |
US20030082561A1 (en) | 2000-07-21 | 2003-05-01 | Takashi Sera | Zinc finger domain recognition code and uses thereof |
MY142915A (en) | 2001-03-23 | 2011-01-31 | Bayer Healthcare Llc | Rho-kinase inhibitors |
JP4329003B2 (ja) | 2001-03-23 | 2009-09-09 | バイエル コーポレイション | Rhoキナーゼ阻害剤 |
JPWO2002100833A1 (ja) | 2001-06-12 | 2004-09-24 | 住友製薬株式会社 | Rhoキナーゼ阻害剤 |
US20030211603A1 (en) | 2001-08-14 | 2003-11-13 | Earp David J. | Reprogramming cells for enhanced differentiation capacity using pluripotent stem cells |
WO2003059913A1 (en) | 2002-01-10 | 2003-07-24 | Bayer Healthcare Ag | Roh-kinase inhibitors |
CA2473910C (en) | 2002-01-23 | 2011-03-15 | Bayer Pharmaceuticals Corporation | Pyrimidine derivatives as rho-kinase inhibitors |
WO2003092762A1 (fr) | 2002-04-30 | 2003-11-13 | Amniotec Inc. | Feuille de type endothelium corneen et procede permettant de la produire |
DE10224242A1 (de) | 2002-05-29 | 2003-12-11 | Max Delbrueck Centrum | Frog Prince, ein Transposonvektor für den Gentransfer bei Wirbeltieren |
WO2004009555A1 (ja) | 2002-07-22 | 2004-01-29 | Asahi Kasei Pharma Corporation | 5−置換イソキノリン誘導体 |
US7422736B2 (en) | 2002-07-26 | 2008-09-09 | Food Industry Research And Development Institute | Somatic pluripotent cells |
CA2400996A1 (en) | 2002-09-03 | 2004-03-03 | Lisa Mckerracher | 1,4-substituted cyclohexane derivatives |
EP2267115B8 (en) | 2003-02-06 | 2014-07-23 | Cellseed Inc. | Anterior ocular segment related cell sheets, three-dimensional structures, and processes for producing the same |
WO2004073761A1 (ja) | 2003-02-20 | 2004-09-02 | Cellseed Inc. | 再生角膜内皮細胞シート、製造方法及びその利用方法 |
US20060104968A1 (en) | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
US7871607B2 (en) | 2003-03-05 | 2011-01-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases |
AU2004242586C1 (en) | 2003-05-28 | 2011-02-24 | Regeneron Pharmaceuticals, Inc. | Method of treating corneal transplant rejection by using VEGF antagonists |
US7300654B2 (en) | 2003-05-28 | 2007-11-27 | Regeneron Pharmaceuticals, Inc. | Method of treating corneal transplant rejection in high risk keratoplasty patients |
US7160894B2 (en) | 2003-06-06 | 2007-01-09 | Asahi Kasei Pharma Corporation | Tricyclic compound |
CA2530389A1 (en) | 2003-07-02 | 2005-01-13 | Biofocus Discovery Limited | Pyrazine and pyridine derivatives as rho kinase inhibitors |
US7147648B2 (en) | 2003-07-08 | 2006-12-12 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Device for cutting and holding a cornea during a transplant procedure |
WO2005039564A1 (en) | 2003-10-02 | 2005-05-06 | Vertex Pharmaceuticals Incorporated | Phthalimide compounds useful as protein kinase inhibitors |
WO2005037198A2 (en) | 2003-10-06 | 2005-04-28 | Glaxo Group Limited | Preparation of 1,7-disubstituted azabenzimidazoles as kinase inhibitors |
US20070004771A1 (en) | 2003-10-06 | 2007-01-04 | Glaxo Group Limited | Preparation of 1,6,7-trisubstituted azabenzimidazoles as kinase inhibitors |
JP4764823B2 (ja) | 2003-10-06 | 2011-09-07 | グラクソ グループ リミテッド | キナーゼ阻害剤としての1,6−二置換アザベンゾイミダゾールの調製 |
EP1675944B1 (en) | 2003-10-10 | 2010-11-24 | Ge Ming Lui | Human corneal endothelial cells and methods of obtaining and culturing cells for corneal cell transplantation |
US20070092550A1 (en) | 2003-10-10 | 2007-04-26 | Cellular Bioengineering, Inc. | Methods and compositions for growing corneal endothelial and related cells on biopolymers and creation of artifical corneal transplants |
JP2007008816A (ja) | 2003-10-15 | 2007-01-18 | Ube Ind Ltd | 新規イソキノリン誘導体 |
ES2426288T3 (es) | 2003-10-15 | 2013-10-22 | Ube Industries, Ltd. | Novedoso derivado de imidazol |
JP2007015928A (ja) | 2003-10-15 | 2007-01-25 | Ube Ind Ltd | 新規オレフィン誘導体 |
US7087369B2 (en) | 2003-12-17 | 2006-08-08 | The Regents Of The University Of California | Cornea preservation medium |
EP1720874A4 (en) | 2004-02-24 | 2010-03-03 | Bioaxone Therapeutique Inc | SUBSTITUTED PIPERIDINE DERIVATIVES IN POSITION 4 |
CA2561724A1 (en) | 2004-04-02 | 2005-11-03 | Vertex Pharmaceuticals Incorporated | Azaindoles useful as inhibitors of rock and other protein kinases |
ES2708384T3 (es) | 2004-09-08 | 2019-04-09 | Wisconsin Alumni Res Found | Cultivo de células madre embrionarias humanas |
EP2479256A1 (en) | 2004-11-04 | 2012-07-25 | Advanced Cell Technology, Inc. | Derivation of embryonic stem cells |
US7893315B2 (en) | 2004-11-04 | 2011-02-22 | Advanced Cell Technology, Inc. | Derivation of embryonic stem cells and embryo-derived cells |
WO2006057270A1 (ja) | 2004-11-26 | 2006-06-01 | Asahi Kasei Pharma Corporation | 含窒素3環化合物 |
EP1835023A4 (en) | 2004-12-09 | 2008-09-10 | Amano Shiro | PRECIPITATING CELL DERIVED FROM HUMAN HORNHAIL ENTHELIAL CELLS, OR DERIVED CELL ASSOCIATION, METHOD FOR THE MANUFACTURE THEREOF, AND METHOD FOR TRANSPLANTING THE PRECURSOR CELL OR THE CELL ASSOCIATION |
US9999497B2 (en) | 2005-01-31 | 2018-06-19 | Yichieh Shiuey | Corneal implants and methods and systems for placement |
WO2006110552A2 (en) | 2005-04-12 | 2006-10-19 | Cleo Cosmetic And Pharmaceutical Co., Llc | Composition and method for in vitro preservation of corneal tissues |
JP5220414B2 (ja) | 2005-08-30 | 2013-06-26 | 旭化成ファーマ株式会社 | スルホンアミド化合物 |
CN101384704B (zh) | 2005-10-12 | 2012-02-08 | 细胞生物工程公司 | 可再吸收的角膜扣状体 |
EP1980274B1 (en) | 2006-01-19 | 2016-03-23 | Senju Pharmaceutical Co., Ltd. | Corneal endothelial preparation which enables cells to grow in vivo |
US20080050423A1 (en) | 2006-08-23 | 2008-02-28 | National Tsing Hua University | Biopolymer-bioengineered cell sheet construct |
KR20210070407A (ko) | 2007-08-29 | 2021-06-14 | 센주 세이야꾸 가부시키가이샤 | 각막 내피 세포 접착 촉진제 |
CA2705465C (en) | 2007-10-30 | 2016-01-19 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Lipoxin a4 protection for cornea endothelial cells |
US8636795B2 (en) | 2008-04-25 | 2014-01-28 | The Regents Of The University Of California | Device to store and inject corneal graft |
US20110166650A1 (en) | 2008-09-04 | 2011-07-07 | Massimo Busin | New technique for preparing, storing and transplanting endothelial grafts |
WO2010096496A2 (en) | 2009-02-17 | 2010-08-26 | Memorial Sloan-Kettering Cancer Center | Methods of neural conversion of human embryonic stem cells |
WO2010099310A1 (en) | 2009-02-26 | 2010-09-02 | Wake Forest University Health Sciences | Endothelial scaffolds |
CA2833173C (en) | 2011-04-20 | 2023-09-05 | University Of Washington Through Its Center For Commercialization | Beta-2 microglobulin-deficient cells |
PT2788472T (pt) | 2011-12-06 | 2019-04-01 | Astellas Inst For Regenerative Medicine | Método de diferenciação dirigida para a produção de células endoteliais corneanas |
EP4253409A3 (en) | 2012-04-17 | 2023-12-06 | University of Washington through its Center for Commercialization | Hla class ii deficient cells, hla class i deficient cells capable of expressing hla class ii proteins, and uses thereof |
US20200063105A1 (en) * | 2017-05-01 | 2020-02-27 | President And Fellows Of Harvard College | Transcription factors controlling differentiation of stem cells |
JP6758631B2 (ja) * | 2017-06-19 | 2020-09-23 | 国立大学法人大阪大学 | 角膜内皮細胞マーカー及びその利用 |
IL277914B1 (en) | 2018-04-11 | 2024-03-01 | Precise Bio 3D Ltd | Corneal implant and biotechnological methods for its preparation |
-
2022
- 2022-05-02 CN CN202280032423.4A patent/CN117242173A/zh active Pending
- 2022-05-02 JP JP2023568269A patent/JP2024519218A/ja active Pending
- 2022-05-02 EP EP22725037.0A patent/EP4334437A1/en active Pending
- 2022-05-02 KR KR1020237041521A patent/KR20240005837A/ko unknown
- 2022-05-02 WO PCT/US2022/027335 patent/WO2022235586A1/en active Application Filing
- 2022-05-02 AU AU2022270611A patent/AU2022270611A1/en active Pending
- 2022-05-02 BR BR112023021993A patent/BR112023021993A2/pt unknown
- 2022-05-02 CA CA3216719A patent/CA3216719A1/en active Pending
- 2022-05-03 TW TW111116689A patent/TW202309274A/zh unknown
Also Published As
Publication number | Publication date |
---|---|
AU2022270611A1 (en) | 2023-10-12 |
JP2024519218A (ja) | 2024-05-09 |
WO2022235586A1 (en) | 2022-11-10 |
CN117242173A (zh) | 2023-12-15 |
EP4334437A1 (en) | 2024-03-13 |
AU2022270611A9 (en) | 2024-02-22 |
BR112023021993A2 (pt) | 2024-02-20 |
CA3216719A1 (en) | 2022-11-10 |
KR20240005837A (ko) | 2024-01-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2020270508B2 (en) | C/EBP alpha short activating RNA compositions and methods of use | |
AU2022201307B2 (en) | Genetically modified cells, tissues, and organs for treating disease | |
CN114176043B (zh) | 用于治疗疾病的遗传修饰的细胞、组织和器官 | |
KR102301464B1 (ko) | 종양 세포에 의한 면역 억제를 감소시키기 위한 방법 및 조성물 | |
AU2023274083A1 (en) | Compositions and methods for treating non-age-associated hearing impairment in a human subject | |
KR101840618B1 (ko) | 종양 억제 유전자에 대한 천연 안티센스 전사체의 억제에 의해 종양 억제 유전자 관련된 질환의 치료 | |
KR20120082906A (ko) | 자가포식현상-향상 유전자 생성물의 조절을 통한 자가포식현상의 조절 방법 | |
KR20160027968A (ko) | Foxp3 발현을 조절하기 위한 조성물 및 방법 | |
KR20200126997A (ko) | 인간 대상체에서의 비-노화-관련 청각 손상의 치료를 위한 조성물 및 방법 | |
KR20210138587A (ko) | 개선된 면역요법을 위한 조합 유전자 표적 | |
DK1939287T3 (en) | Method of gene transfer specific to a trophectodermal cell | |
KR20220157944A (ko) | 인간 대상체에서 비-연령-연관 청각 장애를 치료하기 위한 조성물 및 방법 | |
TW202309274A (zh) | 產生成熟角膜內皮細胞之方法 | |
KR20220077916A (ko) | 세포를 형질세포양 수지상 세포 또는 인터페론 유형 i-생산 세포로 재프로그래밍하기 위한 조성물, 방법 및 이의 용도 | |
US20220395582A1 (en) | Compositions and methods of inducing differentiation of a hair cell | |
KR20190126812A (ko) | 질환 진단용 바이오마커 | |
US20220265798A1 (en) | Cancer vaccine compositions and methods for using same to prevent and/or treat cancer | |
TW202227102A (zh) | 治療脂肪肝病之方法 | |
US20230035235A1 (en) | Swi/snf family chromatin remodeling complexes and uses thereof | |
KR20240005887A (ko) | 성숙한 간세포를 발생시키는 방법 | |
KR20230173074A (ko) | 향상된 이종이식편 생존 및 관용을 위한 하나 이상의 변형된 유전자를 갖는 세포, 조직, 기관, 및 동물 |