Human Genetics

, Volume 131, Issue 4, pp 527–533 | Cite as

Genetic determinants of Tibetan high-altitude adaptation

  • Tatum S. Simonson
  • Donald A. McClain
  • Lynn B. Jorde
  • Josef T. PrchalEmail author
Review Paper


Some highland populations have genetic adaptations that enable their successful existence in a hypoxic environment. Tibetans are protected against many of the harmful responses exhibited by non-adapted populations upon exposure to severe hypoxia, including elevated hemoglobin concentration (i.e., polycythemia). Recent studies have highlighted several genes subject to natural selection in native high-altitude Tibetans. Three of these genes, EPAS1, EGLN1 and PPARA, regulate or are regulated by hypoxia inducible factor, a principal controller of erythropoiesis and other organismal functions. Uncovering the molecular basis of hypoxic adaptation should have implications for understanding hematological and other adaptations involved in hypoxia tolerance. Because the hypoxia response involves a variety of cardiovascular, pulmonary and metabolic functions, this knowledge would improve our understanding of disease mechanisms and could ultimately be translated into targeted therapies for oxygen deprivation, cardiopulmonary and cerebral pathologies, and metabolic disorders such as diabetes and obesity.


Selection Candidate Allele Frequency Difference Chronic Mountain Sickness Tibetan Population Selection Candidate Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Tatum S. Simonson
    • 1
  • Donald A. McClain
    • 2
  • Lynn B. Jorde
    • 1
  • Josef T. Prchal
    • 3
    Email author
  1. 1.Eccles Institute of Human GeneticsUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Endocrinology, Metabolism and DiabetesUniversity of Utah School of MedicineSalt Lake CityUSA
  3. 3.Hematology and Pathology (ARUP)University of Utah School of MedicineSalt Lake CityUSA

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