Human high-altitude adaptation: forward genetics meets the HIF pathway

被引：263

作者：

Bigham, Abigail W. ^{[1
]}

Lee, Frank S. ^{[2
]}

机构：

[1] Univ Michigan, Dept Anthropol, Ann Arbor, MI 48109 USA

[2] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

来源：

GENES & DEVELOPMENT | 2014年 / 28卷 / 20期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

EGLN1; high-altitude adaptation; HIF; hypoxia; PHD2; Tibetan adaptation; HYDROXYLASE DOMAIN PROTEIN-2; ARTERIAL OXYGEN-SATURATION; HYPOXIA-INDUCIBLE FACTORS; MICE PARTIALLY DEFICIENT; PULMONARY-HYPERTENSION; HEMOGLOBIN CONCENTRATION; HETEROZYGOUS DEFICIENCY; ERYTHROCYTOSIS ESTABLISHES; TRANSCRIPTIONAL RESPONSE; PHYSIOLOGICAL-RESPONSES;

D O I：

10.1101/gad.250167.114

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-2 alpha, 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.

引用

页码：2189 / 2204

页数：16

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