Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach 英文参考文献.docVIP

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Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach 英文参考文献.doc

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Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach 英文参考文献

Genome-WideIdentificationofSusceptibilityAllelesfor ViralInfectionsthroughaPopulationGeneticsApproach MatteoFumagalli1,2,UbertoPozzoli1,RacheleCagliani1,GiacomoP.Comi3,NereoBresolin1,3 ,Mario Clerici4,5.,ManuelaSironi1*. 1ScientificInstituteIRCCSE.Medea,BioinformaticLab,BosisioParini(LC),Italy,2BioengineeringDepartment,PolitecnicodiMilano,Milan,Italy,3DinoFerrariCentre, DepartmentofNeurologicalSciences,UniversityofMilan,IRCCSOspedaleMaggiorePoliclinico,MangiagalliandReginaElenaFoundation,Milan,Italy,4Departmentof BiomedicalsciencesandTechnologiesLITASegrate,UniversityofMilan,Milan,Italy,5DonC.GnocchiONLUSFoundationIRCCS,Milan,Italy Abstract Viruseshaveexertedaconstantandpotentselectivepressureonhumangenesthroughoutevolution.Weutilizedthemarks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of differentvirusesinageographicregion)wasusedtomeasurevirus-drivenselectivepressure.Resultsshowedanexcessof variantscorrelatedwithvirusdiversityingenesinvolvedinimmuneresponseandinthebiosynthesisofglycanstructures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteinsthatdirectlyinteractwithviralcomponents.Genome-wideanalysesidentified441variantssignificantlyassociated with virus-diversity; these aremore frequently located within gene regions than expected, andthey map to139 human genes.Analysisoffunctionalrelationshipsamonggenessubjectedtovirus-drivenselectivepressureidentifiedacomplex networkenrichedinviralproducts-interactingproteins.Thenovelapproachtothestudyofinfectiousdiseaseepidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidatesusceptibilityvariantsforviralinfections. Citation:FumagalliM,PozzoliU,CaglianiR,ComiGP,BresolinN,etal.(2010)Genome-WideIdentificationofSusceptibilityAllelesforViralInfectionsthrougha PopulationGeneticsApproach.PLoSGen