Natural selection on EPAS1 (HIF2 alpha) associated with low hemoglobin concentration in Tibetan highlanders
文献类型：期刊论文
| 作者 | Beall CM1; Cavalleri GL2; Knight J5,6; Li CH3; Li JC7; Liang Y8; Zheng YT17; Zeng CQ[*]3; Deng LB3; Elston RC4 |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2010 |
| 卷号 | 107期号:25页码:11459-11464 |
| 关键词 | chronic mountain sickness high altitude human genome variation hypoxia hypoxia-inducible factor |
| 通讯作者 | peter.robbins@dpag.ox.ac.uk ; czeng@big.ac.cn. |
| 英文摘要 | By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3,200 3,500 m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2 alpha, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort of Tibetans residing at 4,200 m, we identified 31 EPAS1 SNPs in high linkage disequilibrium that correlated significantly with hemoglobin concentration. The sex-adjusted hemoglobin concentration was, on average, 0.8 g/dL lower in the major allele homozygotes compared with the heterozygotes. These findings were replicated in a third cohort of Tibetans residing at 4,300 m. The alleles associating with lower hemoglobin concentrations were correlated with the signal from the GWADS study and were observed at greatly elevated frequencies in the Tibetan cohorts compared with the Han. High hemoglobin concentrations are a cardinal feature of chronic mountain sickness offering one plausible mechanism for selection. Alternatively, as EPAS1 is pleiotropic in its effects, selection may have operated on some other aspect of the phenotype. Whichever of these explanations is correct, the evidence for genetic selection at the EPAS1 locus from the GWADS study is supported by the replicated studies associating function with the allelic variants. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by the National Science Foundation; National Institutes of Health National Center for Research Resources, National Institute of General Medical Scien- ces, National Cancer Institute, National Heart, Lung, and Blood Institute; National Natural Science Foundation of China Grant 30890031 and Ministry of Science and Technology Grant 2006DFA31850 (to C.Z.); Chinese Academy of Sciences Grant KSCX2-YW-R-76 and Science and Technology Plan of the Tibet Autonomous Region Grant 2007-2-18 to Beijing Genomics Institute at Shenzhen; and an International Joint Project award from the Royal Soci- ety. This consortium grew from a catalysis meeting sponsored by the Na- tional Science Foundation-supported National Evolutionary Synthesis Center (http://www.NESCent.org). |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/11064]  |
| 专题 | 昆明动物研究所_分子免疫药理学 |
| 作者单位 | 1.Department of Anthropology, Case Western Reserve University, Cleveland, OH 44106-7125 2.Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland 3.Beijing Institute of Genomics, Key Laboratory of Genome Sciences and Information, Chinese Academy of Sciences, Beijing 100029, China 4.School of Biomedical Sciences, Chinese University of Hong Kong, Shatin NT, Hong Kong, China 5.Tibet Academy of Social Sciences, Lhasa 850000, Tibet Autonomous Region, China 6.Department of History, The Centre for Society and Genetics and the Novembre Laboratory, University of California, Los Angeles, CA 90095-7221 7.Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195 8.Department of Epidemiology and Public Health, University College London, London WC1E 6BT, United Kingdom 9.Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 10.Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106-7281 |
| 推荐引用方式 GB/T 7714 | Beall CM,Cavalleri GL,Knight J,et al. Natural selection on EPAS1 (HIF2 alpha) associated with low hemoglobin concentration in Tibetan highlanders[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2010,107(25):11459-11464. |
| APA | Beall CM.,Cavalleri GL.,Knight J.,Li CH.,Li JC.,...&Gao Y.(2010).Natural selection on EPAS1 (HIF2 alpha) associated with low hemoglobin concentration in Tibetan highlanders.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,107(25),11459-11464. |
| MLA | Beall CM,et al."Natural selection on EPAS1 (HIF2 alpha) associated with low hemoglobin concentration in Tibetan highlanders".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 107.25(2010):11459-11464. |
入库方式： OAI收割
来源：昆明动物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。