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:(90203011);(2002AC014):2006-02-28:2006-07-132404200704:1006-9348(2007)04-0297-04SNP李延恩,周艳红(,430074):,(SingleNucleotidePolymorphism,SNP)SNP;SNP,SNP,SNPSNPSNPSNPSNP,SNP:;;;:TP391:BBioinformaticsMethodsandResourcesforSNPFunctionalAnalysisLIYan-en,ZHOUYan-hong(CenterforBioinformatics,HuazhongUniversityofSci&Tech,WuhanHubei430074,China)ABSTRACT:Inthepost-genomicarea,thefastaccumulationofSNPdataavailableinthepublicdomaininrecentyearsenabledtheinsilicofunctionalanalysisoftheSNPswhicharelocatedbothincodingandnon-codingregions.However,theaccuracyofcurrentSNPfunctionalpredictiontoolsisstillnotsatisfactory.AccordingtothetypesofSNPs,abroadreviewofBioinformaticsmethodsavailableispresentedtounderstandthefunctionaleffectsofgeneticvariantsonthegeneproducts.Specialattentionhasbeendrawnonthedeleteriousnon-synonymousSNPspredictionbasedonsequencefeaturesandstructurefeatures.Also,publicSNPresourcesandSNPfunctionalannotationtoolsaresummarized.Theanalysisdemonstratesthattherearealotofunsolvedproblemsandinnovationsinthisfield.KEYWORDS:Singlenucleotidepolymorphism(SNP);Insilicofunctionalanalysis;Bioinformaticsmethods;SNPresourcesandfunctionalannotationtools1(SingleNucleotidePolymorphisms,SNP),DNASNP,90%,dbSNP5SNP,SNPSNP:95%SNP,SNPSNP(rSNP);SNP(cSNP)cSNP,,SNP(sSNP);SNP,SNP(nsSNP),SNPDNARNASNPSNP,SNP,,SNP,SNP(FunctionalSNP,fSNP)SNP,,-SNPfSNP,SNP,)297)[1],SNPSNP,,nsSNPSNPSNP;SNPSNP,SNPSNPSNPSNPSNP2SNPSNPSNP(deleterious),(tolerated)SNP,;SNPSNPSNP2.1SNPSNP(nsSNP)nsSNP,,:SNPSNP1999,Cargill,nsSNPnsSNPBLOSUM62SNP,nsSNP[2],nsSNP,NgHenikoffnsSNP2001,,,(PSSM),nsSNPSIFT[3]SIFTBLOSUM62SIFT,dbSNPnsSNP25%,SIFT,,,2001,SunyaevnsSNP[4],PolyPhen,20%nsSNP,nsSNP,SNPBeta(sn)(sp),,,ChasmannsSNP[5],16,nsSNP,,26%-32%nsSNPFaynsSNP,nsSNP[6]nsSNP2002,SaundersnsSNP[7],CBSIFT,,KarchinnsSNP32[8]2.2SNPSNPSNP(sSNP),,(ExonSplicing)(ExonSplicingEnhancers,ESEs),SNPESE,mRNA,,ESESNP,,BRCA1BRCA2SNP,ESE[9],FairbrotherSNPESE,SNP[10]SNP,,SNP,nsSNPSNPSNP,SNP,CowlesSNP,69,4SNP[11]Pastinen129,23[12],SNP)298)HoogendoornSNPSNP(haplotype)SNP1/3[13],SNPSNPSNP,PupaSNPFinder,ConsiteSNP3SNP3.1SNP/1)DatabaseofSingleNuleotidePolymorphisms(dbSNP)(dbSNP)(NCBI)19989SNP,DNA,:)HumanGenomeVariationDatabase(HGVbase)(HGVbase)(EBI)(EMBL),HGVBaseHGVBaseDNASNP25,;GenBank:)HumanGeneMutationDatabase(HGMD)(HGMD),HGMD,,,HGMD;OMIMGDBGenAtlas:)SNP,SNP,Swiss-ProtSNP;(GDB);HapMapConsortiumSNP;(OMIM)SNP3.2SNPGoldenPath,SNPNCBIdbSNP,SNP,SNP,SNPDNAEMBL-EBISangerEnsemblSNPEnsemblSNPSNP,EnsemblSNPViewSNP,BioMartSNP,SNP,nsSNP,LS-SNP[14]dbSNP28,043nsSNPSNPSNP,KohaneSNPper,MooneyMutDB,LiangTopoSNP,SNP4SNPSNP,,nsSNP,,,;,;,,,cSNPSNP(unbiased)SNP,Miller[15],SNPSNP,Ferrer-Costa[16],WangMoult[17]SNPSNP,SNP,SNP,,SNPSNP)299)GO:[1]CSCarlson,et.a.lMappingcomplexdiseaselociinwhole-genomeassociationstudies[J].Nature.,2004,429(6990):446-452.[2]MCargil,let.a.lCharacterizationofsingle-nucleotidepolymorphismsincodingregionsofhumangenes[J].Nat.Genet.,1999,22(3):231-238.[3]PCNgandSHenikof.fPredictingdeleteriousaminoacidsubstitutions[J].GenomeRes.,2001,11(5):863-874.[4]SSunyaev,et.a.lPredictionofdeleterioushumanalleles[J].Hum.Mo.lGenet.,2001,10(6):591-597.[5]DChasmanandRMAdams.Predictingthefunctionalconsequencesofnon-synonymoussinglenucleotidepolymorphisms:structure-basedassessmentofaminoacidvariation[J].J.Mo.lBio.l,2001,307(2):683-706.[6]JCFay,GJWyckoffandCIWu.Positiveandnegativeselectiononthehumangenome[J].Genetics.,2001,158(3):1227-1234.[7]CTSaundersandDBaker.Evaluationofstructuralandevolutionarycontributionstodeleteriousmutationprediction[[J]].J.Mo.lBio.l,2002,322(4):891-901.[8]RKarchin,et.a.lLS-SNP:large-scaleannotationofcodingnon-synonymousSNPsbasedonmultipleinformationsources[J].Bioinformatics,2005,21(12):2814-2820.[9]HXLiu,et.a.lAmechanismforexonskippingcausedbynonsenseormissensemutationsinBRCA1andothergenes[J].Nat.Genet.,2001,27(1):55-58.[10]WGFairbrother,et.a.lSinglenucleotidepolymorphism-basedvalidationofexonicsplicingenhancers[J].PLoS.Bio.l,2004,2(9):E268.[11]CRCowles,et.a.lDetectionofregulatoryvariationinmousegenes[J].Nat.Genet.,2002,32(3):432-437.[12]TPastinen,et.a.lAsurveyofgeneticandepigeneticvariationaffectinghumangeneexpression[J].PhysiolGenomics.,2004,16(2):184-193.[13]BHoogendoorn,et.a.lFunctionalanalysisofhumanpromoterpolymorphisms[J].Hum.Mo.lGenet.,2003,12(18):2249-2254.[14]RKarchin,et.a.lLS-SNP:large-scaleannotationofcodingnon-synonymousSNPsbasedonmultipleinformationsources[J].Bioinformatics.,2005,21(12):2814-2820.[15]MPMillerandSKumar.Understandinghumandiseasemutationsthroughtheuseofinterspecificgeneticvariation[J].Hum.Mo.lGenet.,2001,10(21):2319-2328.[16]CFerrer-Costa,MOrozcoandXdelaCruz.Characterizationofdisease-associatedsingleaminoacidpolymorphismsintermsofsequenceandstructureproperties[J].J.Mo.lBio,l2002,315(4):771-786.[17]ZWangandJMoult.SNPs,proteinstructure,anddisease[J].Hum.Mutat.,2001,17(4):263-270.[](1979-)(),,,2002(SNP)(1966-)(),,,,,2002,10,21,40,(254):[1]FAckermann.Abstandsregelungmitradar[J].Spektru