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  • Title: GCH1 plays a role in the high-altitude adaptation of Tibetans.
    Author: 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.
    Journal: Zool Res; 2017 May 18; 38(3):155-162. PubMed ID: 28585439.
    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.
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