Selection on Alleles Affecting Human Longevity and Late-Life Disease The Example of Apolipoprotein E 英文参考文献.docVIP

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Selection on Alleles Affecting Human Longevity and Late-Life Disease The Example of Apolipoprotein E 英文参考文献.doc

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Selection on Alleles Affecting Human Longevity and Late-Life Disease The Example of Apolipoprotein E 英文参考文献

SelectiononAllelesAffectingHumanLongevityand Late-LifeDisease:TheExampleofApolipoproteinE FotiosDrenos*¤,ThomasB.L.Kirkwood InstituteforAgeingandHealth,NewcastleUniversity,NewcastleUponTyne,Tyne,UnitedKingdom Abstract Itisoftenclaimedthatgenesaffectinghealthinoldage,suchascardiovascularandAlzheimerdiseases,arebeyondthe reachofnaturalselection.Weshowinasimulationstudybasedonknowngenetic(apolipoproteinE)andnon-geneticrisk factors(gender,diet,smoking,alcohol,exercise)that,becausethereisastatisticaldistributionofagesatwhichthesegenes exerttheirinfluenceonmorbidityandmortality,theeffectsofselectionareinfactnon-negligible.Agradualincreasewith eachgenerationofthee2ande3allelesofthegeneattheexpenseofthee4allelewaspredictedfromthemodel.Thee2 allelefrequencywasfoundtoincreaseslightlymorerapidlythanthatfore3,althoughtherewasnostatisticallysignificant differencebetweenthetwo.Ourresultmayexplaintherecentevolutionaryhistoryoftheepsilon2,3and4allelesofthe apolipoproteinEgeneandhaswiderrelevanceforgenesaffectinghumanlongevity. Citation:DrenosF,KirkwoodTBL(2010)SelectiononAllelesAffectingHumanLongevityandLate-LifeDisease:TheExampleofApolipoproteinE.PLoSONE5(4): e10022.doi:10.1371/journal.pone.0010022 Editor:MattKaeberlein,UniversityofWashington,UnitedStatesofAmerica ReceivedJanuary14,2010;AcceptedMarch13,2010;PublishedApril2,2010 Copyright:?2010Drenos,Kirkwood.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:TheauthorsthanktheDrHadwenTrustforfinancialsupport(/).Thefundershadnoroleinstudydesign,datacollection andanalysis,decisiontopublish,orpreparationofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:F.Drenos@ucl.ac.uk ¤Currentaddress:DivisionofCardiovascularGenetics,DepartmentofMedicine,UniversityCollegeLondon,London,UnitedKingdom Introduction lipoproteinpreferencessuchthat