人白血病相关逆转录病毒基因及其应用

摘要

人白血病相关逆转录病毒基因及其应用,是从人白血病细胞中分离、纯化和克隆获得涉及四种常见类型白血病相关的人类逆转录病毒基因:急性淋巴细胞性白血病,慢性粒细胞性白血病,急性早幼粒细胞性白血病,急性粒单细胞性白血病。本发明不仅论证了人白血病逆转录病毒病因学学说,也阐明了人白血病发病机制,并可研制出新的更有效的白血病早期诊断和预后判断的试剂盒,也可研制出能有效预防和控制人白血病发生和发展的抗病毒疫苗和抗病毒药物。

主权项

1.人白血病相关逆转录病毒基因及其应用，其特征在于：以人白血病细胞通过联合应用多种因子诱导整合状态的前病毒DNA，使其产生病毒颗粒释放到体外细胞培养体系中，应用低温超速密度梯度离心法分离纯化培养液中的病毒颗粒，提取病毒颗粒中的RNA，构建相应cDNA文库，文库筛检与分析，用获得的病毒cDNA作为探针，对白血病细胞内病毒RNA和整合的前病毒DNA进行克隆与鉴定，获得四种常见类型白血病相关的人类逆转录病毒基因：急性淋巴细胞性白血病(ALL，SEQ ID NO.1)慢性粒细胞性白血病(CML，SEQ ID NO.2)，急性早幼粒细胞性白血病(APL或AML-M3，SEQ ID NO.3)，急性粒单细胞性白血病(AML-M4，SEQ ID NO.4)，他们的核酸序列及碱基计数为：(a)SEQ ID NO.1：5′ATG AAG GCA GAA ATA AAG ATG TTC TTT GAA ACC AAT GAG AAC AAA GAC ACA ACAM K A E I K M F F E T N E N K D T T TAC CAG AAT CTC TGG GAC ACA TTC AAA GCA GTG TGT AGA GGG AAA TTT ATA GCAY Q N L W D T F K A V C R G K F I A CTA AAT GCC CAC AAG AGA AAG CAG GAA AGA TCC AAA ATT GAC ACC CTA ACA TCAL N A H K R K Q E R S K I D T L T SCAA TTA AAA GAA CTA GAG AAG CAA GAG CAA ATA CCT TCA AAA GCT AGC AGA AGGQ L K E L E K Q E Q I P S K A S R RCAA GAA ATA ACT AAG ATC AGA GCA GAA CTG AAG GAA ATA GTG ACA CAA AAA ACCQ E I T K I R A E L K E I V T Q K TCTT CAA AAA ATC AAT GAA TCC AGG AGC TGG TTT TTT GAA AAG ATC AAC AAA ATTL Q K I N E S R S W F F E K I N K IGAT AGA CCG CTA GCA AGA CTA ATA AAG AAG AAA AGA GAG AAG AAT CAA ATA CATD R P L A R L I K K K R E K N Q I HGCA ATA AAA AAT GAC AAA GGG GAT ATC ACC ACC AAT CCC ACA GAA ATA CAA ACTA I K N D K G D I T T N P T E I Q TAAC ATC AGA GAA TAC TAT AAA CAC CTC TAT GCA AAT AAA CTG GAA AAT CTA GAAN I R E Y Y K H L Y A N K L E N L EGAA ATG GAT AAA TTC CTC GAC ACA TAC ACC CTC CCA AGA CTA AAC CAG GAA GAAE M D K F L D T Y T L P R L N Q E EGTG GAA TCT CTG AAT AGA CCA ATA ACA GGC TCT GAA ATT GTG GCA ATA ATT AATV E S L N R P I T G S E I V A I I NAGC TTA CCA ACC AAA AAA AGT CCA GGA CCA GAT GGA TTC ACA GCC AAA TTC TACS L P T K K S P G P D G F T A K F YCAG AGG CAT AAG GAG GAG CTG GTA CCA TTC CTT CTG AAA CTA TTC CAA TCA ATAQ R H K E E L V P F L L K L F Q S IGAA AAA GAG GGA ATC CTC CCT AAC TCA TTT TAT GAG GCC AGC GTC ATC CTG ATAE K E G I L P N S F Y E A S V I L ICCA AAG CCT GGC AGA GAC ACA ACA AAA AAA GAG AAT TTT AGA CCA ATA TCC TTGP K P G R D T T K K E N F R P I S LATG AAC ATT GAT GCA AAA ATC CTC AAT AAA ATA CTG GCA AAC CGA ATC CAG CAA M N I D A K I L N K I L A N R I Q Q CTC ATC AAA AAG CTT ATC CAC CAT GAT CAA GTG GGC TTC ATC CTT GGG ATG CAA L I K K L I H H D Q V G F I L G M Q GGC TGC TTC AAC ATA CGA AAA TCA ATA AAT GTA ATC CAC CAT ATA AAC AGA ACC G C F N I R K S I N V I H H I N R T AAA GAC AAA AAC CAG ATG ATT TTC TCA ATA GAT GCA GAA AAG GCC TTT GAC ACA K D K N Q M I F S I D A E K A F D TATT CAA CAG CTC TTC ATG CTA AAA ACT CTC AAT AAA TTA GGT ATT GAT GGG ACG I Q Q L F M L K T L N K L G I D G TTAT CTC AAA ATA ATA AGA GCT ATC TAT GAC AAA CCC ACA GCC AAT ATC ATA CTG Y L K I I R A I Y D K P T A N I I LAAT GGA CAG AAA CTG GAA GCA TTC CCT TTG AAA ACT GGC ACA AGA CAG GGA TGC N G Q K L E A F P L K T G T R Q G CCGT CTC TCA CCA CTC CTA TTC AAC ATA GTG TTG GAA GTT CTG GCC AGG GCA ATC R L S P L L F N I V L E V L A R A IAGG CAG GAG AAG GAA ATA AAA GGC ATT CAA TTA GGA AAA GAG GAA GTC AAA TTG R Q E K E I K G I Q L G K E E V K LTCC CTG TTT GCA GAT GAC ATG ATT TTA TAT CTA GAA AAC CCC ATC GTC TCA GCC S L F A D D M I L Y L E N P I V S ACAA AAT CTC CTT AAG CTG ATA AGC AAC TTC TTC TCT CAA CTC GTC AAA GTC ATT Q N L L K L I S N F F S Q L V K V ICTC TGT CCA TCT TTG TTC TGT TGC TGG TGA 3′ L C P S L F C C W *(b)SEQ ID NO.2： 1 CCCTTTGATC CCGATAGCCC TGAAATCAGC GCATGATTCA CATGGCTTTA GTCCATCAAA 61 ACACAGAAGA CATGAGAAGA AAACTGCAGA AACAGGCTGG GCTTGCAGGG ATGAATACAT 121 GCGCAGAAGA CATGCGAAGA AAACTGCAGA AACAGGCTGG GCTTGCAGGG ATGAATACAT 181 CACAATTACT AGAAATAGCT AGCCAGGTGT TTGTAAACAG GGATGCAGTA AGCCGTAAGG 241 CACAATTACC AGAAATAGCT AGCCAGGTGT TTGTAAACAG GGATGCAGTA AGCCGTAAGG 301 AAAACGGCAA AGAGAATGGA GGTCAGGCCC AGTGAAACAC CGAACTGTGG GTTAGCTGCA 361 GCAATCAGAG GGGCCCCCCC GCAAAGAGGC AAGGGAAGGG GGGTCCTGGG AAAGAAACTC 421 AGCTTGGCTG TCAGAGTTTG CAGCGTAACC AGTGTGCTTA TTGTAAAGAA ATAGGACAGT 481 GGAAGAACAA ATGCCCTCAG CTCAAAAGAA AACAAGGTGA CTCCGAGCAG GAGGCCCCGG 541 ACAAGGAGGA AGGGGCCCTG CTCAACCTGG CTGAAGAGTT ATTGGACTGA CGGAGACCGG 601 GCTCAAGCGT CCCCAAAGAG CCTCTGGTCA GAATGACAGT TGGGGGAAGA GACATTGATT 661 TTCTTGTAGA TAGCGGTGCT GAACATTCGC TAGTAACTGC CGCGGTCGCC CCCTTATCCA 721 AAAAGACTAT TGACGTCATC GGAGCCACGG GGGTTTCAGC AAAGCAAGCT TCCTGCTTGC 781 CTCGGACTTG TACTGTGGGA GGATATCAAG TCATTCATCA GTTTTGGTAC ATGCCTGACT 841 GCCCCTTGCC CTTTTGGGGA AGGGACTTGC TCAGCAAGCT GAGAGCCACT ATCTCTGACA 901 GAGCATGGCT CTTTGCTGCT AAAGTTACCC GGAACAGGAG TCATTATGAC CCTTATGGTC 961 CCCTGAGAGG AGGAATGTAG ACTTTTCTGA ACGGAGCCGG GCCAAGAGAG AAGACCAGCT1021 CTGGCTAAGA GGTGGCCAAG AGTACAGGCA GAACACAACC CTCCGGGATT GGCCAGTTAA1081 GACCGGCACC CAGCCAGTTA GGCACAAACA GGAACCCGTC CCCAGAGAAG CTCTTCAAAG1141 TATCCAGGTC CGTCTCAAGC ACCTAAGAAC TTTTGGAATG ATTGTTCCTT GTCAGTCTCC1201 GTGGAACACT CCCCTCCTGC CTGTTCCCAA GCCACGGACC AAGGACTACC GGCCGATACA1261 AGATTTGCGC TTGCTTAATC AAGCTACACT GACTTTCCAT CCAACAGGAG CTAACCCGTC1321 CGCATTGTTG GGGTTGCTGC CAGCTGAGGA CAGCTGCTTC ACCTGCTTGG ACCCGAAAGA1381 TGCTTTCTTT CCTATCAGAT TAGCCCCTGA GAGGCAGAAT CTGTTTCCCT TTCAGTGGGA1441 AGATCTGGAG TCAGGTGTAC ACTTGGACCG GGCTTCCCCA AGGGTTCAAG AACTCCCCCA1501 CCATCTTCGG GGAGGCATTG GCTCGAGACC TCCAGAAGTT TCCCACCAGA GACCTAGGCT1561 GCGTGTTGCT CAAGTAGGTT GATGACCTTC TGCTGGGACA CCCCACAGCA GTCGGGTGTG1621 CCAAGGGAAC AGATGCCCTA CTCCGGCACC TGGAGGACTG TGGGTATATG GTGTCCAAGA1681 AGAAAGCTCA GATCTGCCGA CAGCAGGTAC GTTACTTGGG AATTTACTAT CCAACAGGGG1741 TCGGAACGCA GCCCGGGATC AGAAAGAAAG CAGGTCATTT GCAATCTAGC GGAGCCTAAG1801 AGCAGAAGGC AAGTGAGAGA ATTCTTAGGA GCTGTGGGAT TTTGTAGACT CTGGGTCCCA1861 AACTTTGCAG TATTAGCCAA GCCTTTGTAT GAGGTCACAA AGGGGGCGGG GACTGGGAAC1921 CTTTGGAATG CGGATCCCAA CAACAGCAAG TCTTTCATGA GTTAAAGGAA AAACTTCTGG1981 CAGCCCCAGC CCTGGGGCTA CCTGACCTGA CAAAGCCTTT TCCATTGTAT GCATCAGAGA2041 GAGAAGAGAT GGCAGCTGGA CTTTGAACCC AAACTGTGGG GCCCTGGCTG AGGCCAGTGG2101 CCTACTTCTC TAAACAACTA GACGGGGTTT CTAAAGGATG GCCCCCCTGT TTGAGGGCCT2161 TGGCAGCAAC TGCCCTGCTA GGACAAGAAG CAAATAAGCT GACTCTTGGG CAAAACCTGA2221 GCATAAAGGC CTCCCATGCT GTGGTGACTT TAATGAATAC TAAAGGACAT CGTTGGCTAA2281 CGAATGCCAG ACTCACCAAG TACCAAATTT TGCTCTGTGA AAATCCCCGT ATAACCATTG2341 AAGTTTGTAA CACCCTACAC CCCGCCACCT TGCTCCTGGT ATCAGAGAGC CCTGTCGAGC2401 CTGATTGTGT AGAACTGTTG GACTCAGTTG ACTCTAGCAG ACCTGACTTC CAGGACCAGC2461 CTTGGGCATC AGTAGACTTG GAACTATACG TGGATGGGAG CAGCTTCTTC AACCCCCAAG2521 GAGAGAGAGG TGCAGGGTGT GCCGTGGTAA CCCTGGACAC TGTTGTTGAA GCCAGATCGC2581 TGCCCCAGGG CACTTCAGCC CAGAAAGCTG AACTCATTGC TTTCATTCGG GCCTTAGAAC2641 TCAGTGAGGG TGGGACTGTC AACATTTACA CTGATTCTTG GTATGTCTTT TTAACCCTTC2701 AAGTGCATGG AGCGTGATAG AAAGAAAAGG GCCTATTGAA CTCTGGGGGA AAAGACAGAA2761 AATATCAACA AGAAATCTTG CAATTATTAG AAGCAGTATG GAAACCCCAC AAGGTGGCAG2821 TTGTGCATTG CAGAAGACAC CAGCGAGCTT CTACCTTGGT GGGTTTGGGG AATTCCCGCA2881 CTGACTCAGA GGCTCGAAAA GCAGCATCTG CCCCCTTCCA GGCATCAGTG CTCCCTCAAG2941 CACCTGATCT TGGACTTACT TCTTCTAAAG AAGAAAAGGA CTTTCTCCAG GTAGAGGGAA3001 GGACAAGTGA TGCAGGAAGG ATGGATTCGG TTACCAGATG GGAGAGTAGC CGTGCCACAC3061 TTGCTAGGAG GTGCAGTTAT ACTGGCTGTG CATGAAACCA CGCATGTAGG TCAGGAGTCA3121 CTGGAAAAGT TGTTAGGCTG GTATTTGTAC ATCTCGCATT TGTCAGCCCT CGCCAAAACG3181 GTGAGGCAGC AGTGTGTTAC CTGCCAACAG CATAATGCGA GGCAAGGTCC AGCCGTTCCA3241 CCCGGCATAC AAGCTTACGG AGCAGCCCCC TTTGAAAATC TCCAGGTAGA CTTCACAGAG3301 ATGACAAAGT GTGGAGATAA CACGTATTTA CTAGTTCTTG CACATACCTA CTCTGGGTGG3361 GTGGAGGCCT ATCCAACATG AACTGAGAAA TCTCGTGAAG TAACCCCTGT GCTTCTTCGA3421 GATCTGATTC CGAGATTTTG ACTGGCCTTA TGGATTGGCT CAGATAACGG GCCTGCGTCT3481 TTGGCTGCCT TGGTACAGAA GACGGCAAAG GTATTGGGGA TCACACGGAA ACTGCATGCC3541 ACCTCCCGGC CTAAGAGTTC CGGAAAGTTG GAGCGGATGA ATCAGACTAT CAAAAATAGT3601 ACTATTATCT TCCCCGCTGG ATATTTAAAA CAACACCACA AGCAAGGGGC CTCAAAGCAC3661 CTGCTAAATT TGAGGGAATG TTATCCTCTC CCCCCCCTCC CCTGACCCTG GATATTAGAG3721 ACAATAACAT TGAGGGAATG TTATCCTCTC CCCACCTCCC CCGGCCCCGG ATATTAGAGA3781 CAATAACACA GGGGTAATGT ACACCCACTG CTTTATTGGG AGTACCATCA TCCTCTCCCT3841 TCTTGAATAT TAGGAGCAGT ATCACACTGC GCGTGTACGC CTGTCGTGAA ATTCTATGGA3901 ATGTCACCCT TTGCCTCCCT GGATATGATG AACAATATCA CGGGGGATGT ACAACTTCCG3961 AGATATTGGC AGTGATATCA TCCTCTCCCC TCTGGAAGTT AGGGAAAATA TCACAGGGGT4021 AGTGTACACC CTCTGGGATG TTGGGATTAA TATCATCCTC CCGCCCACTG GATATTAAAA4081 ACCATATCAC AAGGGCATGT ACACACACTT CGATATTGGT ATTAATACCA TCCTCTCCCT4141 CTTTGGATAT TCGGTGCCAT ATTTCAGGTG GGGTATATAC CACCTGCAAT ATTGGAAGTA4201 ATATGATTTT CTCCACCCCC CACATATCAG AAACAATAAC ACAGGGGGGT GTCAACAACC4261 CCTGCGATAT TTGGAGGAAT ATCATCGTCT CTCCTCAAGA ATATTAAGAA CAATATCGTA4321 GGGGTGGGGG GTGTACACCC CCTTTCATAT TTGATATCAT CCTCTTCCCC CCTGGATATT4381 AGGAACAATA TCAGGAAGGG ATGTACAGAC CCTGCGACCT TTGCTGTCAT ATAATTTTCT4441 CTCCCCTAGA TATTAGGACA AATGTCACTG GGGATGTGAA CAGCCCTGCG ATATTCGGAG4501 TAGTGTCATC CTCATTGGGA ACAACATCAC AGGTGGGGTG TACTGCCTCT GCGATATTGG4561 GAGTAAAATT TTCCTCTCTT CCCCTGGACA TTAGGAAGGG TATCAGAGGG GGAGGGTGTA4621 CATTCCCTGC GATATTCAAC GTAACCTTAT CCTCTCCCTC CCATGGTATT CAGAACAATA4681 AGACAGGAGG GGTGTACACA CCCTGCGATA TTGAGAGTCA TATCATCCTC TTTCGCTCTG4741 GATATTAGGA ACAATATCAC AGGGTTGTGT ACACCCCTTA CAATAGTGGG AGTAATATCA4801 TCCTCTCTCC CTGTGGATAT TAGGAAGAGT ATCACAGGGC TGTGTAAACC CCCTGCGGTA4861 CTGGGAGTAA TATCATCCTC TCTCCCTCTG GATATTAGGA AGATTTTCAC AGGGGTGTGT4921 ACACCCCCTA CGATATTGGG AGTAATATCA TCCTCTCCAC CCAGGAAATG ACTAACAAGG4981 TCACGGGGGA GTGTACTCCC CCTGTGATAT TGGGAGTAAT GTCGTCCTCC CCAAACCTGG5041 ATGTTAGCAA CAGGATCACA GAGGGGGTGT ACACACCCTG CGACATTGGA AATAATAATG5101 ATCCTCTCCC CACCTGGATA TGGGGAAAGA TATCACAGCG CGGGTATACA TTTCCTACGC5161 TGTTAGGAGT AATATCATTC TTTTCCTTTC TGGATATTAG GAAGAATATC ACAGGGGTGC5221 TGTACAATTA CTTCGATATT GGGATACTCT ATTTTCCTGG ATATTGGGCA CAAAAACACA5281 AAAGGGTGTA CAGCCCCTGC GATATTGGGA ATAATAGCAT ACTCTCCTTC CCTGGATGTT5341 AGAAAACAAT ATCATCAGGG CTGAACACCC CCGGCGATAA GGGGAGTCAT AGTGACTCTT5401 TCACAGGCCA TTTGGAACAA TATCACAGGG GGTGTTTACA AACAGGGGTG GTGTACACCC5461 CCTGGGATAT TGGGAGTAAC ATCATTCTCT CCACCTCCGG ATATTAAGAA CAATATCCTG5521 GCGGGAGGTG GTACACCCCC AGTGATATTG GGAATAATGT CATCCTCTCC TTCCCTGGAT5581 ATTCGGAACA ATATCACAGG GGGGTGTACA CCTTCTGTGA TATTGGAAGC AATATCATCC5641 TCTCCCCCGC TGGATATTAG AAAAAATATC ACTCATGGTG TACATCCACT GTGATATTAG5701 GAAGAATATT ACAGGGTGTA CACCCACTCT GATTTTAGGA GAAATAGCTC CCTCAAATGT5761 CACAAATAAT ACCACAGGGT ATACACTGAT GTCTCCCTAG GATATTACAA ATACTATCAC5821 AGGGTGTACA CCCACTGTGA TAACAGGAGT AATACGTCGC AAGGATACTA CCAATAATAT5881 CCCAAGGCCG TACACCCACT ATGACACAGG GAGTGATATC TCCCTAGGGT ATTACGAATA5941 ATATCACAGA ATGTACACCA ATGATGTGCA CCCACGGTGA CATTAGGAGT AATATCAACC6001 CAGGACATAA CCAATAACAC CACAGGGAGT ACAGACATGA TGTACACCGA CAGTGATGTT6061 AGGAGAACTA TCTCCCTAGG ATAATACGAA TAACATCACA GAGTTTACAC ACATGGTATA6121 CACCGAACTA TCTCCCTAGG ATAATACCAA TAACATCACA GAGCGTACAC ACATGGTATA6181 CACCCACTGT GGCACTGGGA CTAATAACTT TCTAAGATAT TATGAATAGC ATCACAGAAT6241 AGAAACACAT GGTGTACACC CACTGTAACA CAAGGTGTAA TTTCTCCCTA GGATATTACG6301 AGTGACATCT CAGTGCGTAC ACACATGGTA AACACCCACT GTGACATTAA GGGTAATATC6361 CCCCTAGGAT ATTACCAATA ACATCACAGG GTGTCCACCC ATGGTGTACA CGCTCTGTGA6421 TGTTAGGGAT AATAACTCCC TAGGATATGA TGAATAATAC CACAGGGTGT ACAGAAACTG6481 TGATATTAGA GGTAATATCG CTCTAGGATA TTATGAATAA TATCACAGGG TGTACATCCA6541 CTGTGATACT GGGAGCAATA TCTCTCTAGG ATAGTACAAA TAATATCACA GAGTGGACAC6601 CCACTGTGAT GTTAGGAGAA ATATCTCTCT GGGATATTAC AAATCATATC ACAGAGTGTA6661 CACACGTGGT GTACATCCAC TTTGCTATTA GGAGTAATAT CTTCCTAGGA CATTACAAAT6721 AACATCGCAG AGTGTACACC CACTGTAATA TTAGGAATCG TATTTCCCTA GGTGATTACA6781 AATACTATCA CAGGGTGTAC ACCCACTGTG ATATTAGGAG TAATATCCTC CTAGGGTATT6841 ACAAATAATT TCACAGTCTG TACACACATG GTGTACACTC ACTGTGATAT TAGGAGTAAT6901 ATCTACCTAG TGGATAACAA ATAACATCGC AGGGTGTACA CCCACTTTGA TATTAGCTGT6961 AATATTTTCC TAAGTTGTTA CAAATAATAT CACAGGGTGT ACGAACAGGG TGTACACTAA7021 CTGTGATATT CAGAGTCGTA TCTCCATAAT ATATTATGAA TAATATCACA GGGTGTACAC7081 CCACTGTATT ATTAGGAGTG ATATCTCTGT AGGATATTAC AATTAATATC ACAGGGTGTG7141 CAGCCACTGT GATATTAGGA GCAATATCTT TCTAGGATAT TACAAACAAT ATCACAGGGT7201 GTATGCTCAC TCTGCTGTCA GGAGCAATAT CTCCCTAGGA TATCCAAAAT AATATCACAG7261 GGTGTACAAT CTCTGCCTTC CAGGTTCTAA GGGATTCTCC TGCTTCAGCC TCCCGAGTAG7321 CTAGGGTTAC CCGCCAGCAC GCCCGGCTAA TTTTTTTTTT ATTTTCACTA GAGACGGGGT7381 TTCACCACGT TGGCCAGGCT GGTCTGGAAC TCCTGACCTC AGGTGATCCG TCGGCCTCGG7441 CCGCCCAAAG TGCTGGGATT ACAGGTGTGA GCCATGGCGC TCGGCCAAGA GTTATATATT7501 AAATTCATTT GGAAACACAG CTCCCATATT TGAGTGTGCA TGTACTTCTA TGAAGAAATG7561 ATGTCAGAAA ACCTAAGGAT GATAATAAAT ATGAAAAGTA ACAGGCATGT GAAAAGGTGT7621 TCCGATTGAG AACTCTAAGG TTCGATTTCG TTTTTAGATA ATGGGGTCCT AGCTCTTGTA7681 TCATCCTCTT ACATATTCTA CATCAAAGGA ATTTGTAGCA CGGTGTCAGA ATAAAATAGA7741 GCGTATTTCA CTGCTTCTTA ATTTCTTTCA ATTAGACTGA GATCTTTTTC TTAAAGAGAG7801 AAGGACATTT TCATTGCATT TTATTTTTTC TGAAAAGAGT AGGCCGTATT TTACTGAGAT7861 CACGGATTTG TTATATATTA AGTTTTGGTC TTCCAACATT CTTCAGTGGG TTTTCTCTAA7921 AGTAGTATGT ACAGAAGGAG TTGAATAGCA AAAAAGTAAA TCACGTAATA ACTCTGAGAT7981 TTTTGGGTTT GTCACAACTG AGAAATATTG CTGATGGCGT ATGGTCCTCA AGTGTGAAAA8041 TGTTCCCTGT GAATTGCTTG CATCCAAAAT ATACACACAG CATTAAGGGC TGGTTTTTAT8101 CTTTTATTTT TCCAATCCTC TTTCCTTCTC AAGGTGTCCA AGACACACGG AGCCACGGAA8161 TCTCACAGGT GTCTGAGAAT TCCTCCTCCT GGGACTCTCA GAGGATCCAG AACTGCAGCC8221 GGTCCTCGCT TTGCTGTCCC TGTCCCTGTC CATGTCCATG TATCTGGTCA CGGTGCTGAG8281 GAACCTGCTC AGCATCCTGG CTGTCAGCTC TGACTCCCAA CTCCACACCC CCATGTACTT8341 CTTCCTCTCC AACCTGTGCT GGGCTGACAT CGGTTTCACC TCGCCCATGG TTCCCAAGAT8401 GATCATGGAC ATGCAGTCGC ATAGCAGAGT CATCTCTCAT GCGGGCTGCC TGACACGGAT8461 GTCTTTCTTG GTCCTTTTTG CATGTATAGA AGACATGCTC CTGACTGTGA TGGCCTATGA8521 CTGCTTTGTA GCCATCTGTC GCCCTCTGCA CTACCCAGTC ATCATGAATC CTCACCTCTG8581 TGTCTTCTTC GTTTTGGTGT CCTTTTTCCT TAGCCTGTTG GATTCCCAGC TGCACAGTTA8641 GATTGTGTTA CAATTCACTT TCTTCAATAA TGTGGAAATT GCTAATTTTG TCTATGAGCC8701 ATCTCAACTT CTCAACCTTG ACTGTTCTGA CACCGTCATC AATAGCGTAT TTATATATTT8761 CGATAGTACT GTTTGGTTTT CTTCCCATTT CAGGGATCCT TTGTCTTAGT ATAAAATTGT8821 CCCCTCCATT CTAAGGATGT CATCGTCAGA TGGGAAGTAT AAAGCCTTCG CCACCTGTGG8881 CTCTCACCTA GCAGTTGTTT GCTGATTTGA TGGAACAGGC ATTGGCATGT ACCTGACTTC8941 AGCTGTGTCA CCACCCCCCA GGAATGGTGT GGCGGCGTCA GTGATGTACG CTGTGGTCAC9001 CCCCATGCTG AACCTTTTCA TCTACAGCCT GAGAAACAGG GACATTCAAA GTGCCCTGCA9061 GAGGCTGAGT AGCAGAACAG TGGAATCTCA TGATCTGTTC CATCCTTTTT CTTGTGTGGG9121 TGAGAAAGGG CAACCACATT AAATCCCTAC ATCTGCAAAT CCTGCCCCTT AGTCACATTC9181 TTTTTGTGGC TTGATGGCTT TTATTCCTTT CCGCATTTCC TTTGTGAATA TTGCTTTCTT9241 CGTTATGCCT TTAACTGGAA TGGGTGAGTA TTCTGGGATC CTCTGTTTAG CAGGAACCTC9301 ATGACAGAAT CCTCTATACC TAGGCGGCCT CTTTTAGTTT CTGAGCAATA ACCCTGTCAT9361 CCAGGTGGAA TCACAACCAT CTTTTTATAT ACACGAAGTC CTCTCTTCAT TTTGGAATTC9421 CCTGAAGACT GACTTTATGG AAACAATGTA CAGGAGGTCC TCCAACACCA CTGGTTGTTC9481 AAAGTTGTGT AGTTATACTG TTGGTGAGGA ATAAGTGGTT TCGCTATATC TAATTTTGCT9541 TAAAGGTGAA GTTTCCAAGA GACTTTCAAA GATGTTAAGT GAGGACATAC TGTAAAT CA9601 AATTCATATC CTCTTCCAGA GTTCATGTGG AATTTCTTTA TAAACTG(c)SEQ ID NO.3： 1 GGCCCCGCCA AGCTTGCATG CCTGCAGGTC AGGAGAAAGA GGAGGAGGAG GAGGAGAAGA 61 AAAAGGAGGA GGAGGAAAAA GAGCAGCAGA AGGAGGAGGA AGAAGAAGAG GAGAAAGAGG 121 AGCAAACTTT GAAAGAATTT TACAGATGCA TGTGGACTAA CTATAAATTA TAAATAGGGT 181 TTATTGGTAT TAGGGTTTTC TTTGTTAGTA TTAGTAACAG AAATTCAACA GGAACAGTCA 241 CAGACTGAAA CTAATGTGAA GTATTGTTAA AAATTTTCCT TTGATTACAT TGCAGAATAT 301 ATACATACAT TTTCTAATTT GTTCAAATAT TTTGTTTGTA TCTGAACCTA CAAAATATTT 361 TCCTTTGCAT GTTGACAAAG TAATTTTTCT TACTGTGATG CTGAACTCCA ATATCTCCTG 421 CCCTTCTCTG ACACATTGTT GTGACTAACC CATTATGCAA ACTGCTGAAA AATGTAGTTC 481 CAGCCTCAAA TCTGTATTGG TCAGTGCCAG CCACTGCTGT ATCTTCATTT TCCAATATTC 541 TTATCAGTAT TCCTTGAGTC ATTAACTTAG TCATATTTAA TGAAAAGTTC TTGTCATAAG 601 ATTACTTACA CTATTCTTTA AATTTCTTCT AAAATCTATT TAGGTTTATG TCAGTAGGCA 661 TTAGGTGTTC TCCACCACAG AACACAAAAA ATCAATCATT TGATTTTCAT GTTCATATTT 721 TCATTCCTCT CTTAATATCT CAAATTACTC TATCTGATTA ATGTAGATAT TTAACAGTTA 781 CTAATTAAAA TAGTCATCAT GCTATCTTTT AGATCAACAG AAGATAAAAA TAAATCATTT 841 AAAATTTTTA TTTTTAATTG ACAAATAATT GCATATATTA TATATTTATG AGGTAAAATA 901 GCTTTTGATA TGTGTTTAAA ATGTGAAATG ATTAAATAAA GCTAATAAAT CTATCACCTC 961 ATATTCATAC CATATTTTTG TGGTGAAAAC ATTTAAAATT CATTCAGTGA TTTTGAAATA1021 TACAATGCAT TATTATTTAT TATTGTCACT ATTCTGTGCA ATGGATGACT AAAGCTCTTT1081 CCTCCTATCT AACCAATCAA AGGGTACAAA TACATCCTTT AATATTCAAC TGTTTAGTGT1141 TATTTCCCAG AATTCTACAA AAGTCTTATA ATGTTATATC ATATATTTCC TTGAAAATAG1201 GCCAGGTGTG GTGACTTATG CCTGTAATCT CAGCACTTTC GGAGGCCGAG GTTGGTGGAT1261 TACTTGAGGT CAAGTGTTCG AGACCAGCCT GACCAACATG GCGAAACCCC GACTCTACTA1321 AAAATACAAA AATTAGCTGG GTGCTGTGGT GGGCTCCTGT AATGCCAGCT ACTCGGAGGT1381 TGAGGCAGGA GAATCGCTTA AACCCGGGAA GATGAGGTTG CAGTGAGCTG AGATCAAGCC1441 AATTCACTCC AGCCTGAGTG ATAGAGTGAG ACTCTTTCTC AAAAAAACAA CAAAACAAAA1501 CAAAACAAAA ACCATCCACC ATTTTGAAGA TAAAATTACA TCTTATTGTA AAGTTTTAAA1561 TCCCAATTGT ATACTATGGA TTTCAATTAT AATTTGTTTT CCTGGAGAGA AAGCTGCTTG1621 CTTTCTTTAA ACATTTGGAT ATTAGGATTT GCTCTAGCAA TTAGTTAAGT ACTGTTTCCA1681 ACATTTACTA GCTGTGTGAC CAACATTCAG TAGCTTTGTC ACCTTGAGGC AAGTTACTTT1741 AAATCTCTGT TCCTCAGTTT TCGTAGCAAG AGAATAGGGA TAATTATCAT ACCTATTTCA1801 TAGGGCTTAT GTGATTTTTG CATTTTGTAA TGCATCAAAG TCCCAACAGT ATAAAGGACT1861 TAACTATTAT TATTACCATC ACTATAATTA TTGATTATTT ATACTTGCTG AGAGCTCATA1921 GTATGCTCTG GAAATAGGAA TAATTTTTGA ATAAGATAAA ATATTATCAG AACATTTAAG1981 ACATTTTCCT GAAATTATGG CTTTTACCTA CATCCTGGCT TCTGGTCTAG AAACTCTTAT2041 AATTTGAGCA GATTAACTAT AATAAAAAAA TCCTCAACAA TCTTACCACT TACTGCCAAT2101 GAAGTTAATG TTCAACTTCA TTAAAATCCG CATTCCTTAT CTGATAAAAT AGATAAGGGA2161 GAAAGAAGGT GGATTTCAAT TCCTCTTCAG AGCCATTAAC AGTAGAAAAA GGCTCATTCA2221 ACTGTCCTAA TTGGTACATT AAATGGGGAC ATGATTATGG CAAAGAAGCC TCAACACGGG2281 CTTTCTCTAG CATCATCCAG AAGTATCTCC TGCTCAGAGA AATAATAAGA TAATAAGGAG2341 AAAAATTATT GTGTATAATA GTCATAAGCA TGGAAAAAAT AAGATGACAG AAGAAGTAGT2401 CCTTGAAAAG GAGAAAGAAC ATTTGCAATC CATTGACAAT ATGAGAAGAG AAAACAAATT2461 ATAGTAAAAA CAACAGAACT TGAATGTGGA GTAGTCCAGA TTTGTGATAC TTTTTGCATA2521 GAAGGGCCCT GTGGGAGGGA AACAAATAAC AAAGTATCAA TTACCCAAAT TTGGCCTCTC2581 AATACAATTC CAGTTCCCCA GAGAGGTGCT ACCCAATTCC TTCATTTTTT TTTAAACAGA2641 ATGTTAAATC TCTTTTTTTC TCCATGTGTC AGAGTGCAGA GAAATGCTTG TGGACAGTTG2701 GAACACTGCT AGACATACAT TAAAAACTTG GTGAAACCTA GACTGATTTG TGGTTTCGGA2761 GATAATTTGT GAATTTTCTC TGCTAACACT TTAGAGGACA TATGGCACTA ACTGAAAGAG2821 GGACTCTATA CATATGGTGG GGTGACAGAT AAAAGACTTC TGGAATAGTA GTGCCAAGAT2881 TGATGAATAT AAAAAAACTT TTGAAAGTAT AACATAGGTG GGTGGCAAGA TGGCTGAATA2941 GGAACAACTC TGGTCTGCAG CTCCCAGCGA GATCAATGCA GAAGGCAGGT GATTTCTGCA3001 TTTCCAACTG AGGTATCCGG CTCATCTCAT TGGGACTGGT TAGACAGTGG GTGCAGCCCA3061 CGGAGGATGA GCCAAAGCAA GGTGGGGCAT CGCTTCACCC TGGAAGCGCA AGCAGTCAGG3121 GAACTCCCTC CCCTAGCCAA GGGAAGCCAT GAGGGACTGT GCCATGAGGA ATGGTGCATT3181 CAGGCCCAGA TATTATGCTT TTCCCATGGT CTTCACAACC CACAGACCAG GAGATTCCCT3241 TGGGTGCCTA CACCACCATG GCCCTGGGTT TCAAGCACAA AACTGGCTGG CCATTTGGGT3301 AGACACTGAG CTAGCTATAG TTTTTTTAAT ACACCGGTGG TACCTGGAAC ACCACCGAAA3361 CAGAACTGTT CACTCTCCTG GAAAGGGAGC TGAAACCAGG GAGCCAGGTG GTCTAGCTCA3421 GCAGATCCCA CCCCCACGGA GCCCAGCAAG CTAAGATCCA CTGGCTTGAA ATCCTCCCTG3481 CCAGCACAGC AGTCTGAAGT CGACCTGGGA CTCTCCAGCT TGGTGGGGGG AGGGGCGTCC3541 ACCATTACTG AAGCTTGAGT AAGCAAGCAG TTTTCCCCTC ACAGTGTAAG CAAAGCCTAC3601 AGGAAGTTGG AACTGGGTCG AGCCCACTGA AGCTCCGAAA AGCCACTGTA GCCAGACTGA3661 ATCTCTAGAT TTCTCCTCTC TGGGCAGGGC ATCTCTGAAA GAAAGGCAGC AGACCCAGTC3721 AGAAGTTTAT AAATAAAACT CCCATCTCCC TGGGACAGAG CACCTAGGGG AAGGGGCAGC3781 TGTGGGTGCA ACTTCAGCAG ACTTAAACAT TCCTGTCTGC CAGCTCTGAA GAGAGCAGCA3841 GATCTCCCAG CACAGCGCTC GAGCTCTGCT AAGGGACAGA CCTGCCTCCT CAAGTGGGTC3901 CCTGCCCCCC GTGCCTCCTG ACTGGCAGAC ACCTCCCAAC AGGGATTTTG ACAGACACCT3961 CATACAGGAG AGCTCTGGCA GGCATCTGGG GGGTGCCCCT CTGGGATGAA GCTTCCAGAG4021 GAAGGAACAG GCAGCAATCT TTGCTGTTTT GCAGCCTCTG CTGGTGATAC CCAGGTAAAC4081 AGGTTCTGGA GTTGACCTCC AGCAAACTCC AGCAGACCTG CATCAGAGGG GCCTGACTGT4141 TAGAAGGAGA ACTAACAAAC AGAAAGGAAT AGCATCAACA TAAAAGAAAA GGACTTCCAC4201 ACAGAAATCC CATCTGAAAC TCACCAACAT CAGAGACCAA ATGTAGATCA ATCCACAAAG4261 ATGAGGAAAA ACCAGCACAA AAAGGCTGAA AACTCCAAAA ACCAGGACGC CTCCTCTCCT4321 CCGAAGCATC TCAACTCCTC ACCAGCAAGG GAACAAAACT GGATGGAGAA TGAGTTTAAT4381 GAATTGACAG AAGTAGGCTT CAGAAGGTGG GTAATAACAA ACCCCTCTGA CCTAAAGGAG4441 CATGTTCTAA CCCAATGCAA GGAAGCTAAG AACCTTGAAA AAGGTTAAAG AAATTGCTAA4501 CTGGAATAAC CAGTTTAGAG AAGAACATAA ATGACCTGAT GGACCTGAAA AACACAGCAC4561 AAGAACTTCG TGAAGCATAT GCAAGTATAA ATAGCCAAAT CAATCAAGCA GAAGAGAGGA4621 TATCAGAGAT TAAAGATCAA CTTAATGAAA TAAAGCATGA AGAGAAGTTT AGAGAATAAA4681 GAATAAAAAG GGATGAACAA AGCCTCCAAG AAATATGGGA CTATGTGAAA ACCTACGTTT4741 GACTGGTGTA CCTGAAAGTG ACAGGGAGAA TGGAACCAAG TTGGAAAACG CTCTTCAGGA4801 TATTATCCAG GAGAACTTCC CCAACCTAGC AAGACAGGCC AACATTCAAA TTCAGGAAAC4861 ACAGAGAACA CCACAAAGAT ACTCCTTGAG GAGAGCAACC CTAGGACACA TAAGTATCAG4921 ATTCACCAAG GTTGAAATGA GGAAAAAATG TTAAGGGTGG CCAGAGAGAA AGGTCAGGTT4981 ACCCACAAAG GGAAGCCCAT CAGACTAACA GCAGTTCTCT TGGCAGAAAC CCTACAAGCC5041 AGAAGAGAGT GGGGGCTAAT ATTCAACACT CTTGAAGAAA AGAATTTTCA ACCCAGAATT5101 TCATAACCAG CCAAACTAAG CTTCATAAGC AAAGGATAAA TAAAATCCTT TACAGACAAG5161 CAAATGCTGA GAGATTTTTG TCACAACTAG GCCTGCCTTG CAAGACCTCC AGAAGGAAGC5221 ACTAAATATG TAAAGGAAAA ACTGGTTCCA GCCACTGCAA AAACATACCA AATTGTAAAG5281 ACTGTCGACA CTATGAATAA ACTACATCAA ATAATGGTCA AAATAACCAG CTAGCATCAT5341 AATGATAGGA TCAAATTCAA GCATAGCAAT ATTAACCTTA AATCTAAGTG GGTTAAATGC5401 CTCAAGTAAA AGATACAGAG AGCCAAATCA GGAGTGAACT CCCATTCACA ATTGCTACAA5461 AGAGAATAAA ATACCTAGGA ATACAATTTA CAAGAAATGT GAAGGACCTC TTCAAGGAGA5521 ACTACAAACC GCTGCTCAAA GAAATAATAG AGGACATAAA CAAATGGAAA AACGTTACAT5581 GTTCCTGGAT AGGAAGAATC AATATCGTGA AAATGGCAGT ACTGCCCAAA GTAATTTATA5641 GATTCAATGA TATACTCATC AAGCTACTAC TGACTTTCTT CACATCATTA GAAAAAACTA5701 CTTTAAATTT CATATGGAAC CAAAAAGAGC CTGTATAGCC AAGAAAATCC TAAGCAAAAA5761 GAAAAAAGCT GGAGGCATCA TGCTACTTAA CTTCAAACTA TACTACAAGG CTACAGTAAC5821 CAAAACAGCA TGGTACTGGT ACCAAAACAG ATATATAGAC CAATGGAACA GAACAGAGCC5881 CTCAGAAATA ATGCCACACA TCTACAACCA TTTGATCTTT GACAAACATG ACAAAAACAA5941 GCAATGGGGA AAGGATTCCC TATTTAATGA ATGGTTTTGG GAAAACTGTC TAGCCATATG6001 CAGAAAACTG AAACTGGACC CCTCCCTTAC ACCTTATACA AATATTAACT CAAGATGGAT6061 TAAAGACTTA AACATAGTAC CCAAAACCAT AAAATCCCTA GAAGAAACGA CTCTAGAGGA6121 TCCCCGG(d)SEQ ID NO.4： 1 CTTGCTGAAG GTGAGGCTTC GCGCTGGCGG TCCATTGCCA AGACTCACCT TCAGCAAGGC 61 CTGATGGCGT TGACCCGCTC CGTGGCGAAG CCGGAATCCT TCTGACGTGA GCATCCTGTC 121 CCGTGCCCTG CTGGGAGCTG TATTGCTCCT TGTAGGCGTT GCCGGGTGGC AGCGGGGGAC 181 GGTAGCTCAG GCAGAGCGCG CCAAAGAGAA CGCCCAGGTC GCCAAGAAAG TGGCCGAGCA 241 GGAGCGGGAC AACGCCATCG CCGTGATCGC GGTAGAGCGC CAGCGGGTCA AGCGGGCCGA 301 GGCAGTGGCC ACCCAGTACG AGCAGGAGAA GGCAGATGCT GAATCGAAAG GCGCGGCTGT 361 CGCTGATGAC CTGCGTGCTG GCAACCTCCG CCTGCAGCAG CGGTGGGCAG GCTGTGAGGC 421 CCGAGTGTCC GACCTTGCCG CCGCCACCGG CGAGCCTGAT GGTGCCGCCG ACGACCGAGC 481 AGACAGTGCG GGGCGAATTG TTCTCGCCGC TGCCCAGTGC GACGCCCAAA TCCGTGGGCT 541 CCAAGCCTTG GTGAGGGCTG ACCGTGAGTG ACATGGGGCG CGCTACCCGC AACGTGGTCA 601 GCGGCTACAA CCGTGATCGT GTGTTCCAGG CTCGCATCTA TGCGCCGGAA CGTCGTGCGC 661 TGATCACGGA CTTCAATGGC GCGCTGCCTA TTGGCGTGAA GATCACCAAG GCCACATGGA 721 ACACCTGGGA CAACTACCCG GCAGTGATGG CAAGCCCGTC AATCGACGTC AGTGGCCGAT 781 CTTGCCAGGT GATGGTCACG GCTCAGGTGG ACGGCATCTC CTGCATCCGC CTGGCGGTAG 841 ACCTCGACAA CGGTGAGCGC TTCGTCGCCC ACCACGTCAT TCAAGTCCTT CCTGCCCGCT 901 ACATGCAGCC AGACAACTGG ATCAACGGGC CCACCCAATT GGTAGCCACG GCATAACGAA 961 ATGGGAAGGC CTAGCAAGTA CAAGCCTGAG TATGCGAAAC AGGCTGAGAA GCTGTGCCTG1021 CTTGGCGCCA CAGATCAGGA GTTGGCGGAT TTCTTCGAGG TTGAGGTCCG GACTGTATAC1081 CGATGGAAGG GCGACTACCC CGACTTTTGT CAGGCCTTAA AGTCTGGCAA GGAAGAGGCA1141 GACGCCCGAG TCGAGCGCTC CCTGTACCAG CAAGCCATCG GCTATGAGCA GGATGAAGTG1201 AAGATCTTCA TGCCCGCTCA GGCTGAGGCT CCTGTCTATG CCCCATATCG GGCGAAGGTG1261 GCGCCGAACG TCACTGCGGC GATCTTCTGG CTGAAGAACC GGAAGAGCCA GGACTGGCGC1321 GACAAGCAGC ACACAGAGCT GACGGGTGCT GACGGCGGGC CAGTCAAACA TGATGTGAGC1381 ATTACGCCTG ACGAGGCATA TCGGCGCCTT ATCAATGGCT GAGATCGACT GGAACGCGCC1441 TGACTATGGG GCGGTCTATG CGCAGCGGAC GGAGCGACTT GAGCGCCTTC GCGAGCAGCC1501 GGAGCTGATC TCCGGGTTGA AGCAGTACTA CGCTGACCGG CCTGCAGACT TCATCTGCGA1561 TTGGGGCATG ACGTTCGACC CCCGCAATGC AGAGATTGGG CTGCCGACGA CAGTCCCATT1621 CCTGCTGTTC CCCAAGCAGC GCGAGTTCAT CGACTTTGTC CATGAGCGCT GGAAGCAGCG1681 CGAGGATTGG CTGGCCGAGA AATCCCGCGA TATGGGCGTT TCCTGGCTCT GCGTGGCATT1741 CGCTGTGTGG ATGTGGCTGT TCCACCCGGG CACGGTGGTT GGATTCGGTA GCCGCAAGGA1801 AGAGTACGTA GACAACCTTG GTGACCCGAA GTCGCTGTTC TGGAAGATTC GCAGCTTCAT1861 CAGCCTTCTG CCAAAAGAGT TTAGGCCGGC AGGCTGGAAT GAGAAGACCT GCGCTCCGTT1921 CATGAGGGTT ATGAACCCGG AGAATGCCTC GGCAATCGTT GGGGAGGCTG GCGACAACAT1981 TGGCCGAGGC AACCGGACAT CCATCTACTT CAAGGATGAA TCAGCGTTCT ATGAACGGCC2041 GGAGATCATC GACGCGGCTT TGTCCCAGAC ATCCAACTGC AAGGGCGACG TATCGACC