Proteome-Wide Analysis of Disease-Associated SNPs That Show Allele-Specific Transcription Factor Binding 英文参考文献.docVIP

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Proteome-Wide Analysis of Disease-Associated SNPs That Show Allele-Specific Transcription Factor Binding 英文参考文献.doc

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Proteome-Wide Analysis of Disease-Associated SNPs That Show Allele-Specific Transcription Factor Binding 英文参考文献

Proteome-WideAnalysisofDisease-AssociatedSNPs ThatShowAllele-SpecificTranscriptionFactorBinding FalkButter1,LucyDavison2,TarViturawong1,MarionScheibe1,MichielVermeulen3,JohnA.Todd2, MatthiasMann1* 1DepartmentofProteomicsandSignalTransduction,MaxPlanckInstituteofBiochemistry,Martinsried,Germany, 2JuvenileDiabetesResearchFoundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke’s Hospital, University of Cambridge,Cambridge,UnitedKingdom,3MolecularCancerResearch,UniversityMedicalCenterUtrecht,Utrecht,TheNetherlands Abstract A causative role for single nucleotide polymorphisms (SNPs) in many genetic disorders has become evident through numerousgenome-wideassociationstudies.However,identificationofthesecommoncausalvariantsandthemolecular mechanisms underlying these associations remains a major challenge. Differential transcription factor binding at a SNP resultinginalteredgeneexpressionisonepossiblemechanism.HereweapplyPWAS(‘‘proteome-wideanalysisofSNPs’’),a methodologybasedonquantitativemassspectrometrythatenablesrapidscreeningofSNPsfordifferentialtranscription factorbinding,to12SNPsthatarehighlyassociatedwithtype1diabetesattheIL2RAlocus,encodingtheinterleukin-2 receptorCD25.Wereportdifferential,allele-specificbindingofthetranscriptionfactorsRUNX1,LEF1,CREB,andTFAP4to IL2RA SNPs rA, rC, rA, and rs2104286*A and demonstrate the functional influence of RUNX1atryreportergeneassay.Thus,PWASmaybeabletocontributetoourunderstandingofthemolecular consequencesofhumangeneticvariabilityunderpinningsusceptibilitytomulti-factorialdisease. Citation:ButterF,DavisonL,ViturawongT,ScheibeM,VermeulenM,etal.(2012)Proteome-WideAnalysisofDisease-AssociatedSNPsThatShowAllele-Specific TranscriptionFactorBinding.PLoSGenet8(9):e1002982.doi:10.1371/journal.pgen.1002982 Editor:GregoryS.Barsh,StanfordUniversitySchoolofMedicine,UnitedStatesofAmerica ReceivedMay2