低压低氧环境下喜马拉雅世居人群HIF通路的改变（英文）

The HIF pathway under the hypobaric hypoxic environment:response of the Himalayans

本综述旨在探讨一些HIF信号通路上的重要基因,包括EGLN1和EPAS1,这些基因可以解释喜马拉雅地区世居人群所具有的与其高原适应有关的一些复杂特征。目前,全基因组扫描和深度测序等高通量技术已经证明了EPAS1和EGLN1是高原世居人群适应高原低压低氧环境的两个最重要的正选基因。世居高原人群在进化过程中出现的对EGLN1和EPAS1基因的特殊选择性变异和单倍体使得世居高原人群远离了慢性高原病等其他高原相关疾病的侵扰。未来基于EGLN1和EPAS1的遗传学和表遗传学的深入研究可能会发现更多与高原适应相关的重要生物标志物。

The goal of this review is to highlight the underlying genetics of the HIF pathway involving EGLN1 and EPAS1 that may explain the complex traits associated with high altitude ( HA) adaptation in the permanent residents of Himalayas. Current high throughput techniques such as whole-genome scan and deep sequencing have shown that EPAS1 and EGLN1 are the two most positively selected genes for adaptation to the hypobaric hypoxic environment at HA. The specific selection of the variants and haplotypes of EGLN1 and EPAS1 has manifested a different response to such an environment preventing the HA natives from chronic mountain sickness and other mountain disorders. Further detailed understanding of the genetic and epigenetic basis of these two molecules may lead to the unraveling of more important biomarkers in relation to adaptation.