人类基因组计划及其发展简史

©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.()JournalofZiboUniversity(Nat.Sci.andEng.Ed.)Vol.3,No.3Sep.,2001:100920452(2001)03200812081,2(1.,250014;2.,255091):.:;:Q755:A:2001205220:(1978),,,,11859,(CharlesDarwin),(TheNaturalSelectionTheory),.,.,,.1865,(GregorMondel),,(Mendel’sLaw).,.1869,(FriedrichMiescher)DNA,.,(WalterFlemming),.,,.1902,(WalterSutton)(meiosis)[1],,.,,,1909,(WilhelmJohannsen)(gene).1933,(TheChromosomeTheoryofInheritance)[2],,..,.1941,(GeorgeBeadle)(EdwardTatum),,.[3]1958.DNA,,,1953DNAX-DNA.T4-,DNA.1953,(JamesWatson)(FrancisCrick)DNA(TheDoubleHelixStructureofDNA),:DNA,,,.,,DNA.18©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(DNAPolymerase).DNA,DNA.,DNA[4].,ArthurRogerDNA(DNAReplicase).,DNA(ThePolymeraseChainReaction,PCR)DNA,DNA.1953,DNA(SemiconservationReplication),,.1958,(MatthewMeselson)(FranklinStahl)[5].DNA,,.1955,JoeHinTjio:.,.48,30.,Tjio46,.DNA,,DNA,.?mRNA(RNA)DNA.RNADNA:,.DNARNA,(CentralDogma).?1961,RobertGuthrie,,..,,..DNA(GeneticCode),DNA.,.(TripletCode),,.,,20.,.DNA,.1968,DNA,(TheRestrictionNucleasesEnzyme)[6].,DNA,DNA.,DNADNA(DNALigase)DNA..DNA,DNA,DNA.DNA,.:.1973,,DNA.,,,(Clone).DNA,DNA.F.SangerDNA.SangerDNA,DNA..DNA,,,.DNA,,(In228()20013©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.)[7].1977,DNAmRNADNA,mRNADNA,.,().mRNADNA,,.,mRNA,.mRNADNA,,..90%,.,.1981,,.1982,NIH(TheNationalInstitutesofHealth)..,,.HuntingtonHDDNA[8].HD,,.,.1993,,4,HD.,DNAPCR(),DNA,.,1987,,400(RFLPs),RFLPsDNA,DNA.RFLPs,,[9].,,,(YAC),DNA.YAC.DNA,,DNA,,YACDNA,DNA.,,DNA,.1989,DNA,24DNA,,:CAGCAGyi-2=xz+X1hDNA,,DNA,,PCR.,(STS)DNA,PCR,.,DNA.PCRSTSDNA,DNA[10].,.,.198412,DOE(TheU.S.DepartmentofEnergy)NIH,.DOE,.,NIHWT(TheWellcomeTrust).1987,DOE(TheHumanGenomeProject),,NIH.1988,.,,DOENIH.1990,DOENIH38:©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.:;32DNA;;DNA;(EthicalLegalandSocialImplication,ELSI)[11].ELSIDOENIH.:,,,.,,,:???,ELSI.ELSI,.,,.,1990,DNA,,BACs.BACDNA,DNA.BACs100,000300,000,YAC..,.,?(ExpressedSequenceTags,EST).ESTmRNADNA,,.(10%).ESTs.,199210,.DNA,DNA(RFLPs)..,,[12].,1990,NIHDOE19935.1995,DNA[13]..,.,.,.,,.6,000,700,000,.DNA.HGP1998100,000.1995,15,086,199,000.1996,...,.FlAVRSAVRFDA,.,,.(MicrobialGenomeProject).DOE1994,.DOE,48()20013©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(5%)DNA,.,,.DNA580,070,470,.1996,.85%,..,.,2023.19967,000,400,000.19965,.DNA,,,.,,.,,.,,:.,.1612,000,000,6,000,1ö3,,.,.,.,,..19969,HGP.280,000(EST),ESTmRNA.280,000EST.,2000,60,000.ESTs.EST,16,000DNA[14].1996,.,.19972,,,,Bermuda.1997,,.,,.,,..,,..4,600,000,4,000.19987..,,..4,400,000,,.58:©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(ShotGun)[15],,,.,,,,HGP.199810,HGP,30,000,1ö3[16].,1993.199810,HGP2003,2003,.NIHDOE19982003,,[17].19993,HGP:200090%,,..,,SNP(SingleNucleotidePolymor2phism).SNP,,,DNA.SNP,PCR.DNA,,.,,.SNP.HGP,,.EEOC(TheEqualEmploymentOpportunityCommission).ADA(TheAmericanswithDisabilitiesAct)1990726..1995,EEOC.ADA.:,,ADA.,.,1996HIPAA(TheHealthInsuranceandAccountabilityAct).HIPAA,....NIH-DOE,,.,.,.,,,SH(TheSecretaryofHealth)HS(TheHumanServices).19986,,SACGT(TheSecretaryof68()20013©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.):,HGP..200028,:.,,,,,.,.,..,.HGP,.20003,:.HGP.:;.,.,.2000,.3,UCBerleleyCelera.,,,,.,,,24.DNA20,.,DNA,78%.2000,HGP2221.Down.20006,DNA,626,90%.,,HGPCelera,.2000,HGP.2000626,.2000626,6Celera2001212.,,.,31.647,33.5,1,2,10.,2%.,,,,.,,,.,2003.DNA,99.99%.,,.,,.78:©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.:[1]SuttonW,etal.TheChromosomesinHeridity[J].BiologicalBulletin1903,4:2312251.[2]GeraldMRandEdwardB,etal.ABriefHistoryofDrosphila’sContributionstoGenomeResearch[J].Science2000,287:221622218.[3]BeadleG,TatumE,etal.GeneticControlofBiochemicalReactionsinNeurospora[J].Proc.Natl.Acad.Sci.USA1941,27:4992506.[4]KornbergA,etal.DNASynthesis[J].SanFrancisco:Freenan,1974.[5]MeselsonM,StahlF.W.etal.TheReplicationofDNAinE.coli.[J]Proc.Natl.Acad.Sci.USA1958,44:6712682.[6]MeselsonM,YuanR.DNARestricationEnzymefromE.coli[J].Nature1968,217:111021114.[7]ChowLT,RobertJM,LewisJB,BrokerTR.AMapofCytoplasmicRNATranscriptsfromLyticAdenovirusType2,DeterminedbyElectronmicroscopyofRNA:DNAHybrids[J].Cell1977,11:8192836.[8]GusellaJ.F,WexlerN.S,ConneallyP.M,etal:APolymerphicDNAMarkerGeneticallyLinkedtoHuntington’sDisease[J].Nature1983,306:2342238.[9]Donis-KellerH,GreenP,HelmsC,etal.AGeneticLinkagemapoftheHumanGenome[J].Cell1987,51:3192337.[10]OlsonM,HoodL,CantorC,BotsteinD.ACommonLanguageforPhysicalmappingoftheHumanGenome[J].Science1989,245:143421435.[11]Wa