A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence
文献类型：期刊论文
| 作者 | Lou HY1; Lu Y1; Lu DS1; Fu RQ1; Wang XJ1,2; Feng QD1; Wu SJ1; Yang YJ3; Li SL3; Kang LL4 |
| 刊名 | AMERICAN JOURNAL OF HUMAN GENETICS
 |
| 出版日期 | 2015 |
| 卷号 | 97期号:1页码:54-66 |
| 通讯作者 | xushua@picb.ac.cn. |
| 英文摘要 | Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p < 10(-15)). We employed long PCR and Sanger sequencing technologies to determine the exact copy number and breakpoints of the TED in 70 additional Tibetan and 182 diverse samples. The TED had identical boundaries (chr2: 46,694,276-46,697,683; hg19) and was 80 kb downstream of EPAS1. Notably, the TED was in strong linkage disequilibrium (LD; r(2) = 0.8) with EPAS1 variants associated with reduced blood concentrations of hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075-14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1. |
| 收录类别 | SCI |
| 资助信息 | These studies were supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS; XDB13040100), by National Natural Science Foundation of China grants (91331204, 31171218, 31260263, and 31260252), and by the Science and Technology Commission of Shanghai Municipality (14YF1406800). S.X. is a Max-Planck Independent ResearchGroupLeaderandamemberoftheCASYouthInnovation Promotion Association. S.X. also gratefully acknowledges the support of the National Program for Top-Notch Young Innovative Talents of the ‘‘Wanren Jihua’’ Project. |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/9421]  |
| 专题 | 昆明动物研究所_比较基因组学 昆明动物研究所_遗传资源与进化国家重点实验室 |
| 作者单位 | 1.Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, Partner Institute for Computational Biology,Shanghai Institutes for Biological Sciences, Chinese Academy ofSciences, Shanghai 200031,China 2.School of Life Science and Technology,Shang- haiTech University, Shanghai 200031, China 3.State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences,Fudan University, Shanghai 200433, China 4.School of Medicine, Xizang University for Nationalities, Xianyang 712082, Shaanxi, China 5.Department of Biochemistry and Molecular Biology, Preclinical Med- icine College, Xinjiang Medical University, Urumqi 830011, China 6.Faculty of Medicine and Health Sciences, UCSI University, Kualal Lumpur Campus, Jalan Choo Lip Kung, Taman Taynton View, 56000 Cheras, Kuala Lumpur, Malaysia 7.Integrated Research Center for Genome Polymorphism, Department of Microbiology, School of Medicine, Catholic University of Korea, Seocho-gu, Seoul 137-701, Korea 8.State Key Laboratory of Genetic Resources and Evo- lution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 9.Collaborative Innovation Center of Genetics and Devel- opment, Shanghai 200438, China |
| 推荐引用方式 GB/T 7714 | Lou HY,Lu Y,Lu DS,et al. A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence[J]. AMERICAN JOURNAL OF HUMAN GENETICS,2015,97(1):54-66. |
| APA | Lou HY.,Lu Y.,Lu DS.,Fu RQ.,Wang XJ.,...&Xu SH[*].(2015).A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence.AMERICAN JOURNAL OF HUMAN GENETICS,97(1),54-66. |
| MLA | Lou HY,et al."A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence".AMERICAN JOURNAL OF HUMAN GENETICS 97.1(2015):54-66. |
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。