Human high-altitude adaptation: forward genetics meets the HIF pathway.
Human high-altitude adaptation: forward genetics meets the HIF pathway.
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DOI：
10.1101/gad.250167.114
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发表时间：
2014-10-15
影响因子：
10.5
通讯作者：
Lee FS
中科院分区：
文献类型：
--
作者：
Bigham AW;Lee FS
人类已在多个地区适应了高海拔的慢性缺氧，最近的全基因组研究表明，这是一种遗传学基础。在一些人群中，已经在低氧诱导因子(HIF)途径中发现了遗传特征，该途径协调对低氧的转录反应。Bigham和Lee的这篇综述讨论了这些关于人类适应高海拔的发现。人类已在多个地区适应了高海拔的慢性缺氧，最近的全基因组研究表明，这是一种遗传学基础。在一些人群中，已经在低氧诱导因子(HIF)途径中发现了遗传特征，该途径协调对低氧的转录反应。在藏族人中，它们被发现存在于HIF2a(EPAS1)基因中，该基因编码HIF-2α，以及编码其关键调节因子之一PHD2的Pro羟基酶结构域蛋白2(PHD2，也称为EGLN1)基因。高海拔适应可能是由于多个基因相互协同作用所致。解开它们的作用机制可以为治疗以慢性缺氧为特征的常见人类疾病提供新的治疗方法。
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. This review by Bigham and Lee discusses these findings on human adaptation to high altitude. 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.
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