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论文题目: Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia
英文论文题目: Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia
第一作者: Peng, Y; Cui, CY; He, YX; Ouzhuluobu; Zhang, H; Yang, DY; Zhang, Q; Bianbazhuoma; Yang, LX; He, YB; Xiang, K; Zhang, XM; Bhandari, S; Shi, P; Yangla; Dejiquzong; Baimakangzhuo; Duojizhuoma; Pan, YY; Cirenyangji; Baimayangji; Gonggalanzi; Bai, CJ; Bianba; Basang; Ciwangsangbu; Xu, SH; Chen, H; Liu, SM; Wu, TY; Qi, XB; Su, B
英文第一作者: Peng, Y; Cui, CY; He, YX; Ouzhuluobu; Zhang, H; Yang, DY; Zhang, Q; Bianbazhuoma; Yang, LX; He, YB; Xiang, K; Zhang, XM; Bhandari, S; Shi, P; Yangla; Dejiquzong; Baimakangzhuo; Duojizhuoma; Pan, YY; Cirenyangji; Baimayangji; Gonggalanzi; Bai, CJ; Bianba; Basang; Ciwangsangbu; Xu, SH; Chen, H; Liu, SM; Wu, TY; Qi, XB; Su, B
联系作者: Qi, XB; Su, B (reprint author), Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Peoples R China.
英文联系作者: Qi, XB; Su, B (reprint author), Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Peoples R China.
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发表年度: 2017
卷: 34
期: 4
页码: 818-830
摘要: Tibetans are well adapted to the hypoxic environments at high altitude, yet the molecular mechanism of this adaptation remains elusive. We reported comprehensive genetic and functional analyses of EPAS1, a gene encoding hypoxia inducible factor 2 alpha ( HIF-2 alpha) with the strongest signal of selection in previous genome-wide scans of Tibetans. We showed that the Tibetan-enriched EPAS1 variants down-regulate expression in human umbilical endothelial cells and placentas. Heterozygous EPAS1 knockout mice display blunted physiological responses to chronic hypoxia, mirroring the situation in Tibetans. Furthermore, we found that the Tibetan version of EPAS1 is not only associated with the relatively low hemoglobin level as a polycythemia protectant, but also is associated with a low pulmonary vasoconstriction response in Tibetans. We propose that the down-regulation of EPAS1 contributes to the molecular basis of Tibetans' adaption to high-altitude hypoxia.
英文摘要: Tibetans are well adapted to the hypoxic environments at high altitude, yet the molecular mechanism of this adaptation remains elusive. We reported comprehensive genetic and functional analyses of EPAS1, a gene encoding hypoxia inducible factor 2 alpha ( HIF-2 alpha) with the strongest signal of selection in previous genome-wide scans of Tibetans. We showed that the Tibetan-enriched EPAS1 variants down-regulate expression in human umbilical endothelial cells and placentas. Heterozygous EPAS1 knockout mice display blunted physiological responses to chronic hypoxia, mirroring the situation in Tibetans. Furthermore, we found that the Tibetan version of EPAS1 is not only associated with the relatively low hemoglobin level as a polycythemia protectant, but also is associated with a low pulmonary vasoconstriction response in Tibetans. We propose that the down-regulation of EPAS1 contributes to the molecular basis of Tibetans' adaption to high-altitude hypoxia.
刊物名称: MOLECULAR BIOLOGY AND EVOLUTION
英文刊物名称: MOLECULAR BIOLOGY AND EVOLUTION
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学科: Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity
英文学科: Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity
影响因子: 6.202
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论文类别: Article
英文论文类别: Article
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