Affymetrix生物芯片解决方案概述.docx

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Affymetrix生物芯片解决方案概述

Affymetrix生物芯片解决方案概述

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部分文章及链接(点击文章标题可以浏览全文)

胚胎及成体干细胞表达谱分析   SCIENCEVOL3022003

Commenton"'Stemness':

TranscriptionalProfilingofEmbryonicandAdultStemCells"and"AStemCellMolecularSignature"(I) 

Abstract

Ramalho-Santosetal.

(1)andIvanovaetal.

(2),comparingthesamethree"stemcells"—embryonicstemcells(ESCs);neuralstemcells(NSCs),referredtoasneuralprogenitor/stemcells(NPCs)inthepresentstudy;andhematopoieticstemcells(HSCs)—withtheirdifferentiatedcounterparts,eachidentifiedalistofcommonlyexpressed"stemness"genes,proposedtobeimportantforconferringthefunctionalcharacteristicsofstemcells.Theabilitytocaptureexpressionprofilesofcellsusingmicroarraysoffersthepossibilityofdefiningastemcellbyitsconstellationofactivegenes.Anintriguingquestion,however,iswhetherthefunctionalcommonalities(self-renewalandpluripotency)(3)amongstemcellscanbedefinedatthegeneticlevel.Doallstemcellsexpressasimilarsetof"stemness"genesnecessaryfortheiruniqueproperties,ordodifferentstemcellsexpressdifferentsetsofgenesthatconferstemness?

拟南芥基因组插入突变表达谱分析   SCIENCEVOL3012003

Genome-WideInsertionalMutagenesisofArabidopsisthaliana 

Abstract

Over225,000independentAgrobacteriumtransferredDNA(T-DNA)insertioneventsinthegenomeofthereferenceplantArabidopsisthalianahavebeencreatedthatrepresentnearsaturationofthegenespace.Thepreciselocationsweredeterminedformorethan88,000T-DNAinsertions,whichresultedintheidentificationofmutationsinmorethan21,700ofthe29,454predictedArabidopsisgenes.Genome-wideanalysisofthedistributionofintegrationeventsrevealedtheexistenceofalargeintegrationsitebiasatboththechromosomeandgenelevels.Insertionmutationswereidentifiedingenesthatareregulatedinresponsetotheplanthormoneethylene. 

寡核苷酸微阵列技术对结肠腺瘤、腺癌的基因表达谱分析   CancerResearch61(7),3124-30,2001

Transcriptionalgeneexpressionprofilesofcolorectaladenoma,adenocarcinoma,andnormaltissueexaminedbyoligonucleotidearrays

Abstract

Usinganoligonucleotidearraycontainingsequencescomplementaryto3200full-lengthhumancDNAsand3400expressedsequencetags(GeneChip,Affymetrix),mRNAexpressionpatternswereprobedin18colonadenocarcinomasand4adenomas.Pairednormaltissuewasavailableandanalyzedforeachofthetumors.Relativelyfewchangesintranscriptexpressionareassociatedwithcoloncancer.Nineteentranscripts(0.48%ofthosedetected)hadatleast4–10.5-foldhighermRNAexpressionincarcinomacomparedwithpairednormalsamples,whereas47transcripts(1.3%ofthosedetected)hadatleast4–38-foldorlowerexpressioninthetumortissuecomparedwiththenormalsamples.Someofthesedifferenceswereconfirmedbyreversetranscription-PCR.Manyofthesetranscriptswerealreadyknowntobeabnormallyexpressedinneoplastictissueingeneral,orcoloncancerinparticular,andseveralofthesedifferenceswerealsoobservedinpremalignantadenomasamples.Atwo-wayhierarchicalclusteringalgorithmsuccessfullydistinguishedadenomafromadenocarcinomaandnormaltissue,generatingaphylogenetictreethatappropriatelyrepresentedtheclinicalrelationshipbetweenthethreetissuetypesincludedintheanalysis.Thissupportstheconceptthatgenome-wideexpressionprofilingmaypermitamolecularclassificationofsolidtumors.

利用DNA微阵列监测药物代谢及毒理相关基因的表达   PhysiologicalGenomics5(4),161-70,2001

MonitoringexpressionofgenesinvolvedindrugmetabolismandtoxicologyusingDNAmicroarrays.

Abstract

OligonucleotideDNAmicroarrayswereinvestigatedforutilityinmeasuringglobalexpressionprofilesofdrugmetabolismgenes.Thisstudywasperformedtoinvestigatethefeasibilityofusingmicroarraytechnologytominimizethelong,expensiveprocessoftestingdrugcandidatesforsafetyinanimals.Inanevaluationofhybridizationspecificity,microarraytechnologyfromAffymetrixdistinguishedgenesuptoathresholdof90%DNAidentity.OligonucleotidesrepresentinghumancytochromeP-450geneCYP3A5showedheterologoushybridizationtoCYP3A4andCYP3A7RNAs.ThesegenescouldbeclearlydistinguishedbyselectingasubsetofoligonucleotidesthathybridizedselectivelytoCYP3A5.Furthervalidationofthetechnologywasperformedbymeasuringgeneexpressionprofilesinliversofratstreatedwithvehicle,3-methylcholanthrene(3MC),phenobarbital,dexamethasone,orclofibrateandbyconfirmingdataforsixgenesusingquantitativeRT-PCR.Responsesofdrugmetabolismgenes,includingCYPs,epoxidehydrolases(EHs),UDP-glucuronosyltransferases(UGTs),glutathionesulfotransferases(GSTs),sulfotransferases(STs),drugtransportergenes,andperoxisomalgenes,tothesewell-studiedcompoundsagreedwellwith,andextended,publishedobservations.Additionalgeneregulatoryresponseswerenotedthatcharacterizemetaboliceffectsorstressresponsestothesecompounds.Thusmicroarraytechnologycanprovideafacileoverviewofgeneexpressionresponsesrelevanttodrugmetabolismandtoxicology.

表达图谱分析揭示不同细胞遗传学背景下的急性粒细胞白血病的生物学本质的区别  1124–1129PNASJanuary30,2001vol.98no.3

Expressionprofilingrevealsfundamentalbiologicaldifferencesinacutemyeloidleukemiawithisolatedtrisomy8andnormalcytogenetics

Abstract

Acutemyeloidleukemia(AML)isaheterogeneousgroupofdiseases.Normalcytogenetics(CN)constitutesthesinglelargestgroup,whiletrisomy8(+8)asasoleabnormalityisthemostfrequenttrisomy.Howtrisomycontributestotumorigenesisisunknown.Weusedoligonucleotide-basedDNAmicroarraystostudyglobalgeneexpressioninAML+8patientswith+8asthesolechromosomalabnormalityandAML-CNpatients.CD34+cellspurifiedfromnormalbonemarrow(BM)werealsoanalyzedasarepresentativeheterogeneouspopulationofstemandprogenitorcells.ExpressionpatternsofAMLpatientswereclearlydistinctfromthoseofCD34+cellsofnormalindividuals.WeshowthatAML+8blastsoverexpressgenesonchromosome8,estimatedat32%onaverage,suggestinggene-dosageeffectsunderlyingAML+8.Systematicanalysisbycellularfunctionindicatedup-regulationofgenesinvolvedincelladhesioninbothgroupsofAMLcomparedwithCD34+blastsfromnormalindividuals.Perhapsmostinterestingly,apoptosis-regulatinggenesweresignificantlydown-regulatedinAML+8comparedwithAML-CN.WeconcludethattheclinicalandcytogeneticheterogeneityofAMLisduetofundamentalbiologicaldifferences. 

利用SNP微阵列进行小细胞肺癌的杂合性的丢失(LOH)分析  NatureBiotechnology18(9),1001-5,2000

Loss-of-heterozygosityanalysisofsmall-celllungcarcinomasusingsingle-nucleotidepolymorphismarrays

Abstract

Humancancersarisebyacombinationofdiscretemutationsandchromosomalalterations.Lossofheterozygosity(LOH)ofchromosomalregionsbearingmutatedtumorsuppressorgenesisakeyeventintheevolutionofepithelialandmesenchymaltumors.GlobalpatternsofLOHcanbeunderstoodthroughallelotypingoftumorswithpolymorphicgeneticmarkers.Simplesequencelengthpolymorphisms(SSLPs,ormicrosatellites)arereliablegeneticmarkersforstudyingLOH,butonlyamodestnumberofSSLPsareusedinLOHstudiesbecausethegenotypingprocedureisrathertedious.Here,wereporttheuseofahighlyparallelapproachtogenotypelargenumbersofsingle-nucleotidepolymorphisms(SNPs)forLOH,inwhichsamplesaregenotypedfornearly1,500locibyperforming24polymerasechainreactions(PCR),poolingtheresultingamplificationproductsandhybridizingthemixturetoahigh-densityoligonucleotidearray.WecharacterizetheresultsofLOHanalysesonhumansmall-celllungcancer(SCLC)andcontrolDNAsamplesbyhybridization.WeshowthatthepatternsofLOHareconsistentwiththoseobtainedbyanalysiswithbothSSLPsandcomparativegenomichybridization(CGH),whereasamplificationsrarelyaredetectedbytheSNParray.TheresultsvalidatetheuseofSNParrayhybridizationfortumorstudies.

小肠内寄主与微生物之间共生关系的分子水平分析  Science291(5505),881-4,2001

Molecularanalysisofcommensalhost-microbialrelationshipsintheintestine

Abstract

Humanbeingscontaincomplexsocietiesofindigenousmicrobes,yetlittleisknownabouthowresidentbacteriashapeourphysiology.Wecolonizedgerm-freemicewithBacteroidesthetaiotaomicron,aprominentcomponentofthenormalmouseandhumanintestinalmicroflora.GlobalintestinaltranscriptionalresponsestocolonizationwereobservedwithDNAmicroarrays,andthecellularoriginsofselectedresponseswereestablishedbylaser-capturemicrodissection.Theresultsrevealthatthiscommensalbacteriummodulatesexpressionofgenesinvolvedinseveralimportantintestinalfunctions,includingnutrientabsorption,mucosalbarrierfortification,xenobioticmetabolism,angiogenesis,andpostnatalintestinalmaturation.Thesefindingsprovideperspectivesabouttheessentialnatureoftheinteractionsbetweenresidentmicroorganismsandtheirhosts. 

生物时钟对拟南芥信号传导途径中相关基因的表达调控 Science290(5499),2110-3,2000

OrchestratedtranscriptionofkeypathwaysinArabidopsisbythecircadianclock

Abstract

Likemostorganisms,plantshaveendogenousbiologicalclocksthatcoordinateinternaleventswiththeexternalenvironment.Weusedhigh

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