title: Sherpas share genetic variations with Tibetans for high-altitude adaptation.
abstract: BACKGROUND
  Sherpas, a highlander population living in Khumbu region of Nepal, are well known for their superior climbing ability in Himalayas. However, the genetic basis of their adaptation to high-altitude environments remains elusive.
  
  
  METHODS
  We collected DNA samples of 582 Sherpas from Nepal and Tibetan Autonomous Region of China, and we measured their hemoglobin levels and degrees of blood oxygen saturation. We genotyped 29EPAS1SNPs, twoEGLN1SNPs and the TED polymorphism (3.4 kb deletion) in Sherpas. We also performed genetic association analysis among these sequence variants with phenotypic data.
  
  
  RESULTS
  We found similar allele frequencies on the tested 32 variants of these genes in Sherpas and Tibetans. Sherpa individuals carrying the derived alleles ofEPAS1(rs113305133, rs116611511 and rs12467821),EGLN1(rs186996510 and rs12097901) and TED have lower hemoglobin levels when compared with those wild-type allele carriers. Most of theEPAS1variants showing significant association with hemoglobin levels in Tibetans were replicated in Sherpas.
  
  
  CONCLUSIONS
  The shared sequence variants and hemoglobin trait between Sherpas and Tibetans indicate a shared genetic basis for high-altitude adaptation, consistent with the proposal that Sherpas are in fact a recently derived population from Tibetans and they inherited adaptive variants for high-altitude adaptation from their Tibetan ancestors.
authors.affiliation: State Key Laboratory of Genetic Resources and EvolutionKunming Institute of ZoologyChinese Academy of SciencesKunming650223China; Kunming College of Life ScienceUniversity of Chinese Academy of SciencesBeijing100049China; Nepal Academy of Science and TechnologyGPO Box: 3323, KhumaltarLalitpurNepal.
authors.forename: Sushil
authors.initials: S
authors.lastname: Bhandari
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: High Altitude Medical Research Center School of Medicine Tibetan University Lhasa 850000 China.
authors.forename: Chaoying
authors.initials: C
authors.lastname: Cui
authors.affiliation: High Altitude Medical Research Center School of Medicine Tibetan University Lhasa 850000 China.
authors.lastname: Yangla
authors.affiliation: High Altitude Medical Research Center School of Medicine Tibetan University Lhasa 850000 China.
authors.forename: Lan
authors.initials: L
authors.lastname: Liu
authors.affiliation: High Altitude Medical Research Center School of Medicine Tibetan University Lhasa 850000 China.
authors.lastname: Ouzhuluobu
authors.affiliation: High Altitude Medical Research Center School of Medicine Tibetan University Lhasa 850000 China.
authors.lastname: Baimakangzhuo
authors.affiliation: High Altitude Medical Research Center School of Medicine Tibetan University Lhasa 850000 China.
authors.lastname: Gonggalanzi
authors.affiliation: High Altitude Medical Research Center School of Medicine Tibetan University Lhasa 850000 China.
authors.forename: Caijuan
authors.initials: C
authors.lastname: Bai
authors.affiliation: High Altitude Medical Research Center School of Medicine Tibetan University Lhasa 850000 China.
authors.lastname: Bianba
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Genetic Resources and EvolutionKunming Institute of ZoologyChinese Academy of SciencesKunming650223China; Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming650500China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.affiliation: National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Xining 810012 China.
authors.forename: Shiming
authors.initials: S
authors.lastname: Liu
authors.affiliation: National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Xining 810012 China.
authors.lastname: Gengdeng
authors.affiliation: National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Xining 810012 China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China.
authors.forename: Bing
authors.initials: B
authors.lastname: Su
keywords: Genetic adaptation; Sherpa; Tibetan; high altitude; hypoxia