Positive selection on the osteoarthritis-risk and decreased-height associated variants at the GDF5 gene in East Asians.
GDF5 is a member of the bone morphogenetic protein (BMP) gene family, and plays an important role in the development of the skeletal system. Variants of the gene are associated with osteoarthritis and height in some human populations. 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 selection in the East Asian population, especially the haplotypes carrying the derived alleles of 5' UTR SNPs rs143384 and rs143383. The derived alleles of rs143384 and rs143383, which are associated with a risk of osteoarthritis and decreased height, have high frequencies in non-Africans and show strong extended haplotype homozygosity and high population differentiation in East Asian. It is concluded that positive selection has driven the rapid evolution of the two osteoarthritis osteoarthritis-risk and decreased height associated variants of the human GDF5 gene, and supports the suggestion that the reduction in body size during the terminal Pleistocene and Holocene period might have been an adaptive process influenced by genetic factors.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Dong-Dong
DD
Wu
Gui-Mei
GM
Li
Wei
W
Jin
Yan
Y
Li
Ya-Ping
YP
Zhang
D020121:5' Untranslated Regions; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001827:Body Height; D002681:China; D002874:Chromosome Mapping; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation; D055428:Growth Differentiation Factor 5 / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D010003:Osteoarthritis / Q000175:diagnosis* / Q000235:genetics*; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D012306:Risk
D020121:5' Untranslated Regions; C525893:GDF5 protein, human; D005819:Genetic Markers; D055428:Growth Differentiation Factor 5