Genetic Variation and Population Substructure in Outbred CD-1 Mice Implications for Genome-Wide Association Studies 英文参考文献.docVIP

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Genetic Variation and Population Substructure in Outbred CD-1 Mice Implications for Genome-Wide Association Studies 英文参考文献.doc

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Genetic Variation and Population Substructure in Outbred CD-1 Mice Implications for Genome-Wide Association Studies 英文参考文献

GeneticVariationandPopulationSubstructurein OutbredCD-1Mice:ImplicationsforGenome-Wide AssociationStudies KimberlyA.Aldinger1,GretaSokoloff2,DavidM.Rosenberg1,AbrahamA.Palmer1,2,3,KathleenJ. Millen1,2,4 * 1Committee on Neurobiology, The University of Chicago, Chicago, Illinois, United States of America, 2Department of Human Genetics, The University of Chicago, Chicago,Illinois,UnitedStatesofAmerica,3DepartmentofPsychiatryandBehavioralNeuroscience,TheUniversityofChicago,Chicago,Illinois,UnitedStatesofAmerica, 4DepartmentofNeurology,TheUniversityofChicago,Chicago,Illinois,UnitedStatesofAmerica Abstract Outbredlaboratorymousepopulationsarewidelyusedinbiomedicalresearch.Sincelittleisknownaboutthedegreeof geneticvariationpresentinthesepopulations,theyarenotwidelyusedforgeneticstudies.Commerciallyavailableoutbred CD-1 mice are drawn from an extremely large breeding population that has accumulated many recombination events, which is desirable for genome-wide association studies. We therefore examined the degree of genome-wide variation withinCD-1micetoinvestigatetheirsuitabilityforgeneticstudies.TheCD-1mousegenomedisplayspatternsoflinkage disequilibrium and heterogeneity similar to wild-caught mice. Population substructure and phenotypic differences were observedamongCD-1miceobtainedfromdifferentbreedingfacilities.DifferencesingeneticvariationamongCD-1mice fromdistinctfacilitiesweresimilartogeneticdifferencesdetectedbetweencloselyrelatedhumanpopulations,consistent with a founder effect. This first large-scale genetic analysis of the outbred CD-1 mouse strain provides important considerationsforthedesignandanalysisofgeneticstudiesinCD-1mice. Citation:AldingerKA,SokoloffG,RosenbergDM,PalmerAA,MillenKJ(2009)GeneticVariationandPopulationSubstructureinOutbredCD-1Mice:Implications forGenome-WideAssociationStudies.PLoSONE4(3):e4729.doi:10.1371/journal.pone.0004729 Editor:WimE.Crusio,CentreNationaldelaRechercheScientifique,France ReceivedOctober23,2008;AcceptedJanuary22,2009;Pub