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GCH1 plays a role in the high-altitude adaptation of Tibetans.

ABSTRACT: 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.

SUBMITTER: Guo YB

PROVIDER: S-EPMC5460084 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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GCH1 plays a role in the high-altitude adaptation of Tibetans.

Guo Yong-Bo YB He Yao-Xi YX Cui Chao-Ying CY Ouzhu Luobu L Baima Kangzhuo K Duoji Zhuoma Z Deji Quzong Q Bian Ba B Peng Yi Y Bai Cai-Juan CJ Gongga Lanzi L Pan Yong-Yue YY Qu la Kang Min M Ciren Yangji Y Baima Yangji Y Guo Wei W Yang la Zhang Hui H Zhang Xiao-Ming XM Zheng Wang-Shan WS Xu Shu-Hua SH Chen Hua H Zhao Sheng-Guo SG Cai Yuan Y Liu Shi-Ming SM Wu Tian-Yi TY Qi Xue-Bin XB Su Bing B

Zoological research 20170501 3

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. C ...[more]

PMID: 28585439

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Project description:Since their arrival in the Tibetan Plateau during the Neolithic Age, Tibetans have been well-adapted to extreme environmental conditions and possess genetic variation that reflect their living environment and migratory history. To investigate the origin of Tibetans and the genetic basis of adaptation in a rigorous environment, we genotyped 30 Tibetan individuals with more than one million SNP markers. Our findings suggested that Tibetans, together with the Yi people, were descendants of Tibeto-Burmans who diverged from ancient settlers of East Asia. The valleys of the Hengduan Mountain range may be a major migration route. We also identified a set of positively-selected genes that belong to functional classes of the embryonic, female gonad, and blood vessel developments, as well as response to hypoxia. Most of these genes were highly correlated with population-specific and beneficial phenotypes, such as high infant survival rate and the absence of chronic mountain sickness. Genetic features of Tibetans have been broadly investigated, but the properties of copy number variation (CNV) have not been well examined. To get a preliminary view of CNV in Tibetans, we scanned 29 Tibetan genomes with the Illumina Human-1 M high-resolution genotyping microarray and identified 139 putative copy number variable regions (CNVRs), consisting of 70 deletions, 61 duplications, and 8 multi-allelic loci. Thirty-four of the 139 CNVRs showed differential allele frequencies versus other East-Asian populations, with P values ,0.0001. These results indicated a distinct pattern of CNVR allele frequency distribution in Tibetans. The Tibetan CNVRs are enriched for genes in the disease class of human reproduction (such as genes from the DAZ, BPY2, CDY, and HLA-DQ and -DR gene clusters) and biological process categories of ‘‘response to DNA damage stimulus’’ and ‘‘DNA repair’’ (such as RAD51, RAD52, and MRE11A). These genes are related to the adaptive traits of high infant birth weight and darker skin tone of Tibetans, and may be attributed to recent local adaptation. Our results provide a different view of genetic diversity in Tibetans and new insights into their high-altitude adaptation.

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GCH1 plays a role in the high-altitude adaptation of Tibetans.

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<i>GCH1</i> plays a role in the high-altitude adaptation of Tibetans.

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