title: Genetic evidence for high-altitude adaptation in Tibet.
abstract: Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia-response pathways in humans.
authors.affiliation: Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Tatum S
authors.initials: TS
authors.lastname: Simonson
authors.forename: Yingzhong
authors.initials: Y
authors.lastname: Yang
authors.forename: Chad D
authors.initials: CD
authors.lastname: Huff
authors.forename: Haixia
authors.initials: H
authors.lastname: Yun
authors.forename: Ga
authors.initials: G
authors.lastname: Qin
authors.forename: David J
authors.initials: DJ
authors.lastname: Witherspoon
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Bai
authors.forename: Felipe R
authors.initials: FR
authors.lastname: Lorenzo
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Xing
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Jorde
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
authors.forename: RiLi
authors.initials: R
authors.lastname: Ge
mesh_terms: D000064:Acclimatization; D000531:Altitude; D044466:Asian People / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D016014:Linear Models; D008297:Male; D010100:Oxygen; D047493:PPAR alpha / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics*; D012641:Selection, Genetic; D015398:Signal Transduction; D018609:Tibet
chemical_list: D006454:Hemoglobins; D051793:Hypoxia-Inducible Factor 1; D047493:PPAR alpha; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D010100:Oxygen