Positive Selection on the Osteoarthritis-Risk and Decreased-Height Associated Variants at the GDF5 Gene in East Asians 英文参考文献.docVIP
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Positive Selection on the Osteoarthritis-Risk and Decreased-Height Associated Variants at the GDF5 Gene in East Asians 英文参考文献
PositiveSelectionontheOsteoarthritis-Riskand
Decreased-HeightAssociatedVariantsattheGDF5Gene
inEastAsians
Dong-DongWu1.,Gui-MeiLi2.,WeiJin2,YanLi1,Ya-PingZhang1,2*
1StateKeyLaboratoryofGeneticResourcesandEvolution,KunmingInstituteofZoology,ChineseAcademyofSciences,Kunming,China,2LaboratoryforConservation
andUtilizationofBio-resource,YunnanUniversity,Kunming,China
Abstract
GDF5isamemberofthebonemorphogeneticprotein(BMP)genefamily,andplaysanimportantroleinthedevelopment
oftheskeletalsystem.Variantsofthegeneareassociatedwithosteoarthritisandheightinsomehumanpopulations.Here,
we resequenced the gene in individuals from four geographically separated human populations, and found that the
evolution of the promoter region deviated from neutral expectations, with the sequence evolution driven by positive
selectionintheEastAsianpopulation,especiallythehaplotypescarryingthederivedallelesof59UTRSNPsrs143384and
rs143383. The derived allelesof rs143384 andrs143383, which are associated with arisk of osteoarthritis and decreased
height, have high frequencies in non-Africans and show strong extended haplotype homozygosity and high population
differentiationinEastAsian.Itisconcludedthatpositiveselectionhasdriventherapidevolutionofthetwoosteoarthritis
osteoarthritis-riskanddecreasedheightassociatedvariantsofthehumanGDF5gene,andsupportsthesuggestionthatthe
reduction in body size during the terminal Pleistocene and Holocene period might have been an adaptive process
influencedbygeneticfactors.
Citation:WuD-D,LiG-M,JinW,LiY,ZhangY-P(2012)PositiveSelectionontheOsteoarthritis-RiskandDecreased-HeightAssociatedVariantsattheGDF5Gene
inEastAsians.PLoSONE7(8):e42553.doi:10.1371/journal.pone.0042553
Editor:ThomasMailund,AarhusUniversity,Denmark
ReceivedMarch6,2012;AcceptedJuly10,2012;PublishedAugust14,2012
Copyright:?2012Wuetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted
use,distribution,andreproductioninanymedium,providedt
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