title: Human high-altitude adaptation: forward genetics meets the HIF pathway.
abstract: Humans have adapted to the chronic hypoxia of high altitude in several locations, and recent genome-wide studies have indicated a genetic basis. In some populations, genetic signatures have been identified in the hypoxia-inducible factor (HIF) pathway, which orchestrates the transcriptional response to hypoxia. In Tibetans, they have been found in the HIF2A (EPAS1) gene, which encodes for HIF-2α, and the prolyl hydroxylase domain protein 2 (PHD2, also known as EGLN1) gene, which encodes for one of its key regulators, PHD2. High-altitude adaptation may be due to multiple genes that act in concert with one another. Unraveling their mechanism of action can offer new therapeutic approaches toward treating common human diseases characterized by chronic hypoxia.
authors.affiliation: Department of Anthropology, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: Abigail W
authors.initials: AW
authors.lastname: Bigham
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA franklee@mail.med.upenn.edu.
authors.forename: Frank S
authors.initials: FS
authors.lastname: Lee
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000531:Altitude; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000235:genetics; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D000099162:Endothelial PAS Domain-Containing Protein 1; C490190:EGLN1 protein, human
keywords: EGLN1; HIF; PHD2; Tibetan adaptation; high-altitude adaptation; hypoxia