Measures of Autozygosity in Decline Globalization, Urbanization, and Its Implications for Medical Genetics 英文参考文献.docVIP

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Measures of Autozygosity in Decline Globalization, Urbanization, and Its Implications for Medical Genetics 英文参考文献.doc

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Measures of Autozygosity in Decline Globalization, Urbanization, and Its Implications for Medical Genetics 英文参考文献

MeasuresofAutozygosityinDecline:Globalization, Urbanization,andItsImplicationsforMedicalGenetics MichaelA.Nalls1,2,JavierSimon-Sanchez1,3,J.RaphaelGibbs1,4,CoroPaisan-Ruiz4,JoseTomasBras1, ToshikoTanaka5,MarMatarin1,SonjaScholz1,4,CharlesWeitz6,TamaraB.Harris2,LuigiFerrucci5 ,John Hardy4,AndrewB.Singleton1,7* 1LaboratoryofNeurogenetics,IntramuralResearchProgram,NationalInstituteonAging,Bethesda,Maryland,UnitedStatesofAmerica,2LaboratoryofEpidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Maryland, United States of America, 3Unidad de Gene′tica Molecular, Departamento deGeno′micayProteo′mica,Instituto deBiomedicinadeValencia-CSIC,Valencia, Spain, 4Department ofMolecularNeuroscienceandRetaLilaWeston Laboratories, Institute of Neurology, London, United Kingdom, 5Longitudinal Studies Section, Intramural Research Program, National Institute on Aging, Bethesda, Maryland,UnitedStatesofAmerica, 6DepartmentofAnthropology,BiologicalAnthropologyProgram,TempleUniversity,Philadelphia,Pennsylvania, UnitedStatesof America,7DepartmentofPublicHealthSciences,CenterforPublicHealthGenomics,UniversityofVirginia,Charlottesville,Virginia,UnitedStatesofAmerica Abstract Thisresearchinvestigatestheinfluenceofdemographicfactorsonhumangeneticsub-structure.Inourdiscoverycohort,we showsignificantdemographictrendsfordecreasingautozygosityassociatedwithpopulationvariationinchronologicalage. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1Mb in length in a representativepopulationof809unrelatedNorthAmericansofEuropeandescentranginginchronologicalagefrom19–99 yearsold.Thesehomozygoustractsmadeupapopulationaverageof42Mbofthegenomecorrespondingto1.6%ofthe entiregenome,witheachhomozygoustractanaverageof1.5Mbinlength.Runsofhomozygosityaresteadilydecreasing insizeandfrequencyastimeprogress