Adaptations to Climate in Candidate Genes for Common Metabolic Disorders 英文参考文献.docVIP

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Adaptations to Climate in Candidate Genes for Common Metabolic Disorders 英文参考文献.doc

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Adaptations to Climate in Candidate Genes for Common Metabolic Disorders 英文参考文献

AdaptationstoClimateinCandidateGenes forCommonMetabolicDisorders Angela M. Hancock1,David B.Witonsky1,Adam S.Gordon1,Gidon Eshel2¤,Jonathan K.Pritchard1,Graham Coop1, Anna DiRienzo1* 1DepartmentofHumanGenetics,UniversityofChicago,Chicago,Illinois,UnitedStatesofAmerica,2DepartmentofGeophysicalSciences,UniversityofChicago,Illinois, UnitedStatesofAmerica Evolutionarypressuresduetovariationinclimateplayanimportantroleinshapingphenotypicvariationamongand withinspeciesandhavebeenshowntoinfluencevariationinphenotypessuchasbodyshapeandsizeamonghumans. Genesinvolvedinenergymetabolismarelikelytobecentraltoheatandcoldtolerance.Totestthehypothesisthat climateshapedvariationinmetabolismgenesinhumans,weusedabioinformaticsapproachbasedonnetworktheory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwidepopulations(includingthe52intheHumanGenomeDiversityProjectpanel)andfoundcorrelationswith climatevariablesusingrankcorrelationanalysisandanewlydevelopedmethodtermedBayesiangeographicanalysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patternsofallelefrequencyduetopopulationhistoryalone.Fornearlyallclimatevariables,wefoundanexcessof genicSNPsinthetailofthedistributionsoftheteststatisticscomparedtothecontrolSNPs,implyingthatmetabolic genesasagroupshowsignalsofspatiallyvaryingselection.AmongourstrongestsignalswereseveralSNPs(e.g.,LEPR R109K, FABP2 A54T) that had previously been associated with phenotypes directly related to cold tolerance. Since variationinclimatemaybecorrelatedwithotheraspectsofenvironmentalvariation,itispossiblethatsomeofthe signalsthatwedetectedreflectselectivepressuresotherthanclimate.Nevertheless,ourresultsareconsistentwiththe ideathatclimatehasbeenanimportantselectivepressureactingoncandidategenesforcommonmetabolicdisorders. Citation:HancockAM,WitonskyDB,GordonAS,EshelG,PritchardJK,etal.(2008)Adaptationstoclimateincandidateg