Evidence for Positive Selection on the Osteogenin (BMP3) Gene in Human Populations 英文参考文献.docVIP

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Evidence for Positive Selection on the Osteogenin (BMP3) Gene in Human Populations 英文参考文献.doc

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Evidence for Positive Selection on the Osteogenin (BMP3) Gene in Human Populations 英文参考文献

EvidenceforPositiveSelectionontheOsteogenin (BMP3)GeneinHumanPopulations Dong-DongWu1,3.,WeiJin2.,Xiao-DanHao1,3,NelsonLeungSangTang4,5,6,Ya-PingZhang1,2,4 * 1StateKeyLaboratoryofGeneticResourcesandEvolution,KunmingInstituteofZoology,ChineseAcademyofSciences,Kunming,China,2LaboratoryforConservation andUtilizationofBio-resource,YunnanUniversity,Kunming,China,3GraduateSchooloftheChineseAcademyofSciences,Beijing,China,4KIZ/CUHKJointLaboratoryof BioresourcesandMolecularResearchinCommonDiseases,Kunming,China,5DepartmentofChemicalPathology,FacultyofMedicine,TheChineseUniversityofHong Kong,HongKong,SpecialAdministrativeRegion,People’sRepublicofChina,6LaboratoryforGeneticsofDiseaseSusceptibility,LiKaShingInstituteofHealthSciences, TheChineseUniversityofHongKong,HongKong,SpecialAdministrativeRegion,People’sRepublicofChina Abstract Background: Human skeletal system has evolved rapidly since the dispersal of modern humans from Africa, potentially driven by selection and adaptation. Osteogenin (BMP3) plays an important role in skeletal development and bone osteogenesis as an antagonist of the osteogenic bone morphogenetic proteins, and negatively regulates bone mineral density. Methodology/PrincipalFindings:Here,weresequencedtheBMP3genefromindividualsinfourgeographicallyseparated modernhumanpopulations.FeaturessupportiveofpositiveselectionintheBMP3genewerefoundincludingthepresence ofanexcessofnonsynonymousmutationsinmodernhumans,andasignificantlylowergeneticdiversitythatdeviatesfrom neutrality.TheprevalenthaplotypesofthefirstexonregioninEuropeansdemonstratedfeaturesoflong-rangehaplotype homogeneity.IncontrastwithfindingsinEuropean,thederivedalleleSNPArg192Glnshowshigherextendedhaplotype homozygosity in East Asian. The worldwide allele frequency distribution of SNP shows not only a high-derived allele frequencyinAsians,butalsoinAmericans,whichissuggestiveoffunctionaladaptation. Conclusions/Significance:Inconclusion,weprovideevidenceforrecentpositiveselectionoperatinguponacruci