细胞生物学课件chapter10

Genomicsand邱小2009-3-分子Genomicsand邱小2009-3-分子生物学双语课程，北京师范大学生命科学学1ThecompletesetofgenesforThecompletesetofgenesforanProteome:Theallproteinsencodedbyanorganism's2KeyGenomicsisthestudyKeyGenomicsisthestudyofsize,physicalstructure,andsequenceinformationcontainedinanorganism’sDNA.ProteomicsprovidesacomprehensiveviewofhowthestructuresandfunctionsofalltheproteinsinaspecifictypeofcellareBioinformaticsexploresthemeaningofinformationcontainedinthesequencedata.344GenomeandGeneExpressionGenomeandGeneExpressionDNAmicroarray(GeneProteomeand51.GenomesandHumanGenome1.GenomesandHumanGenomeProject620世纪的人类自然科学史上三大科学计20世纪的人类自然科学史上三大科学计Human7HumangenomeThehumangenomeprojectwasinitiatedin1989withthegoalofHumangenomeThehumangenomeprojectwasinitiatedin1989withthegoalofsequencingthe3billionbase-pairhumangenomein15years.TheNationalInstitutesofHealthandtheDepartmentofEnergyinstitutedthejointproject.Twentycentersfrom6countriesincludingChinacontributed.8Venter’swords"youcandoignitedVenter’swords"youcandoignitedthemostfeverishracemodernscienceByOct.1998,theHGPhadmanagedtoassembleonlyafractionofthecode(6%).Then,J.CraigVenterhadcalmlyinformedtheHGPleaderthathewasformingaprivatecompany(CeleraGenomics)todecodethehumangenomehimself.9OnJun26,2000,PresidenttogetherOnJun26,2000,PresidenttogetherwithCraigVentorandFrancisCollins(theHGPleader)declaredthecompletionofthehumangenomedraft.J.CraigTheformerpresidentandfounderofCeleraGenomics,theJ.CraigTheformerpresidentandfounderofCeleraGenomics,the2007Time100mostinfluentialpeopleintheworld.OnSept.4,2007,thefirstcomplete(six-billion-letter)genomeofanindividual—Venter'sownDNAsequence–waspublished.SomeofthesequencesVenter'sgenomeareassociatedwithincreasedriskantisocialbehavior,Alzheimer'sandcardiovasculardiseases.ThispublicationshowspromiseforpersonalizedmedicineviaTimeMagazine'snumberthreein2008'sTop10ScientificDiscoveriesoutlininghisworktoinventthegeneticinformationforawholenewbacterium.Shotgun ThegenomewasrandomlyshearedintomanyShotgun Thegenomewasrandomlyshearedintomanyrandomfragmentswithanaveragesizeof1kb,andclonedintroavector.(Preparewhatyouaregoingtoshot)IndividualrecombinantDNAclonesarerandomlypickedtoprepareDNAforsequencingonanautomatedsequencer.ShotgunSequenceSequenceShotgunSequenceSequenceHumangenomeproject-EstimatedHumangenomeproject-Estimated27,894~1.1-1.4%aretranslatedintoproteins.Fruitfly:13,000Human:Fruitfly:13,000Human:27,894Thesurprisinglysmallnumberofgenesinthehumangenome(<30,000identified)wasamajorsurprisefromtheproject.Itisbelievedthatnon-codingDNAharborsItisbelievedthatnon-codingDNAharbors WhatelsemakehumansdifferentfromotherorganismsRolesWhatelsemakehumansdifferentfromotherorganismsRolesofnon-codingGeneregulation,modification(i.e.ChromosomalLocation,quantity,timingofTissue-specificproteinProteinRNARolesofRNAingeneRNAediting(changesmadetoTranslationalcontrol(atAlterationsinprotein-proteinSinglenucleotidepolymorphisms(SNPs)aresinglebasesataparticularlocuswhereindividualpeoplehavedifferencesintheirsequences.Singlenucleotidepolymorphisms(SNPs)aresinglebasesataparticularlocuswhereindividualpeoplehavedifferencesintheirsequences.1/1000bpinhumangenomesdifferin<1%ofSNPsareexpectedtoimpactproteinSNPsmakedifferenthumanWhatcanwebenefitfromWhatcanwebenefitfromUsegenomicsequencestopredictdiseasesforanUsegenomicsequencestoinventnewtypesofmedication(e.g.,newvaccines)Discoverhowsinglenucleotidepolymorphisms(SNPs)cancausediseasesIdentifynewlyemergingUnderstandtheoriginofDesignnovelgenomestofitforthespecialAndsoon深圳华大基深圳华大基因研究GeneExpressionDNAAlsoGeneExpressionDNAAlsoknownasGeneAllowssimultaneousmeasurementoftheleveloftranscriptionforeverygeneinagenome(geneexpression)HowdowemanufactureaHowdowemanufactureaStartwithindividualgenesofaAmplifyallofthemusingpolymerasechainreaction“Spot”themonamedium,e.g.anordinaryglassmicroscopeEachspotisabout100µmincDNA:complementaryDNA(preparedfromcDNA:complementaryDNA(preparedfromGeneExpressionEachspotinthismicroarraycontainsDNAfromoneofthegenesinthegenome.Thedifferentcolorsindicateconditionsunderwhichthegenesareexpressed.Here,GeneExpressionEachspotinthismicroarraycontainsDNAfromoneofthegenesinthegenome.Thedifferentcolorsindicateconditionsunderwhichthegenesareexpressed.Here,greenspotsrepresentsmRNAsabundantearlyindevelopment,redRNAsareabundantlaterinProteomeandProteomeandMSisamethodinMSisamethodinwhichthemassofverysmallsamplesofamaterialcanbedetermined.TheNobelPrizeinChemistryTheNobelPrizeinChemistryforthedevelopmentofmethodsforidentificationandstructureanalysesofbiologicalmacromoleculesKoichiTheNobelPrizeinKoichiTheNobelPrizeinChemistryOnedayinFebruaryof1985,insteadofusingCobaltUltraFineMetalPowder(UFMP)asamatrix,Imistakenlyusedaglycerin-UFMPmixedmatrix.Inoticedthismistakeimmediately,butIthought,"Mottai-nai!"attheideaofthrowingthemixtureaway.IfIallowedtheglycerintoevaporate,IthoughtthatIcouldstillmakeuseoftheUFMP,soIplacedthemixtureinthevacuumchambertodryitout.ThinkingthatIcouldevenspeedupthedryingprocessbyirradiatingthemixturewiththelaser,Iswitchedonthelaserbeam.4.a.NationalCenterforBiotechnologyInformationNationalLibraryofMedicine,Health,USA.4.a.NationalCenterforBiotechnologyInformationNationalLibraryofMedicine,Health,USA.National proteomicsSwissInstituteofBioinformatics(SIB)NCBIcreatespublicdatabases,NCBIcreatespublicdatabases,conductsresear