GCH1 plays a role in the high-altitude adaptation of Tibetans.
GCH1 plays a role in the high-altitude adaptation of Tibetans.
复制标题
GCH1在藏族高原适应中发挥作用
DOI：
10.24272/j.issn.2095-8137.2017.037
复制
发表时间：
2017-05-18
影响因子：
4.9
通讯作者：
Su B
中科院分区：
文献类型：
--
作者：
Guo YB;He YX;Cui CY;Ouzhu L;Baima K;Duoji Z;Deji Q;Bian B;Peng Y;Bai CJ;Gongga L;Pan YY;Qu L;Kang M;Ciren Y;Baima Y;Guo W;Yang L;Zhang H;Zhang XM;Zheng WS;Xu SH;Chen H;Zhao SG;Cai Y;Liu SM;Wu TY;Qi XB;Su B
西藏人对高原缺氧适应性很强。以前的全基因组扫描报告了许多这种适应的候选基因，但只有少数被研究。在这里，我们报告的缺氧基因（GCH 1，GTP-环水解酶I），参与维持一氧化氮合成酶（NOS）的功能和正常的血压，藏人窝藏许多潜在的适应性变异。我们重新测序了一个80.8 kb的片段，涵盖了整个基因区的GCH 1在50个无关的藏族。结合以前发表的数据，我们证明了许多GCH 1变异显示高原藏人和低地汉族人之间的深刻分歧。中性测试证实了藏人GCH 1上的积极达尔文选择信号。此外，关联分析表明，藏族版本的GCH 1与藏族的多个生理性状，包括血液中的一氧化氮浓度，血氧饱和度，血红蛋白浓度显着相关。综上所述，我们认为GCH 1在藏族高原低氧遗传适应中起一定作用。
Tibetans are well adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene (GCH1, GTP-cyclohydrolase I), involved in maintaining nitric oxide synthetase (NOS) function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans. Combined with previously published data, we demonstrated many GCH1 variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation, and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.