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Sequencing of 50 human exomes reveals adaptation to high altitude.


ABSTRACT: Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP's association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude.

SUBMITTER: Yi X 

PROVIDER: S-EPMC3711608 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Sequencing of 50 human exomes reveals adaptation to high altitude.

Yi Xin X   Liang Yu Y   Huerta-Sanchez Emilia E   Jin Xin X   Cuo Zha Xi Ping ZX   Pool John E JE   Xu Xun X   Jiang Hui H   Vinckenbosch Nicolas N   Korneliussen Thorfinn Sand TS   Zheng Hancheng H   Liu Tao T   He Weiming W   Li Kui K   Luo Ruibang R   Nie Xifang X   Wu Honglong H   Zhao Meiru M   Cao Hongzhi H   Zou Jing J   Shan Ying Y   Li Shuzheng S   Yang Qi Q   Asan   Ni Peixiang P   Tian Geng G   Xu Junming J   Liu Xiao X   Jiang Tao T   Wu Renhua R   Zhou Guangyu G   Tang Meifang M   Qin Junjie J   Wang Tong T   Feng Shuijian S   Li Guohong G   Huasang   Luosang Jiangbai J   Wang Wei W   Chen Fang F   Wang Yading Y   Zheng Xiaoguang X   Li Zhuo Z   Bianba Zhuoma Z   Yang Ge G   Wang Xinping X   Tang Shuhui S   Gao Guoyi G   Chen Yong Y   Luo Zhen Z   Gusang Lamu L   Cao Zheng Z   Zhang Qinghui Q   Ouyang Weihan W   Ren Xiaoli X   Liang Huiqing H   Zheng Huisong H   Huang Yebo Y   Li Jingxiang J   Bolund Lars L   Kristiansen Karsten K   Li Yingrui Y   Zhang Yong Y   Zhang Xiuqing X   Li Ruiqiang R   Li Songgang S   Yang Huanming H   Nielsen Rasmus R   Wang Jun J   Wang Jian J  

Science (New York, N.Y.) 20100701 5987


Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involve  ...[more]

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