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  1. 050 医学部, 大学院医学系研究科 (Faculty&Graduate School of Medicine)
  2. 0501 学術論文 (Journal Articles)

Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas

http://hdl.handle.net/10091/17571
7af16d38-87f1-4e58-a73f-9dc6fa0be287
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Genetic_Variants_EPAS1_Contribute_Adaptation.pdf Genetic_Variants_EPAS1_Contribute_Adaptation.pdf (311.2 kB)
item type 学術雑誌論文 / Journal Article(1)
公開日 2014-06-05
タイトル
タイトル Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas
言語
言語 eng
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ journal article
著者 Hanaoka, Masayuki

× Hanaoka, Masayuki

WEKO 6815

Hanaoka, Masayuki

Search repository
Droma, Yunden

× Droma, Yunden

WEKO 6816

Droma, Yunden

Search repository
Basnyat, Buddha

× Basnyat, Buddha

WEKO 6817

Basnyat, Buddha

Search repository
Ito, Michiko

× Ito, Michiko

WEKO 6818

Ito, Michiko

Search repository
Kobayashi, Nobumitsu

× Kobayashi, Nobumitsu

WEKO 6819

Kobayashi, Nobumitsu

Search repository
Katsuyama, Yoshihiko

× Katsuyama, Yoshihiko

WEKO 6820

Katsuyama, Yoshihiko

Search repository
Kubo, Keishi

× Kubo, Keishi

WEKO 6821

Kubo, Keishi

Search repository
Ota, Masao

× Ota, Masao

WEKO 6822

Ota, Masao

Search repository
信州大学研究者総覧へのリンク
Hanaoka, Masayuki
http://soar-rd.shinshu-u.ac.jp/profile/ja.yCLmHVkh.html
信州大学研究者総覧へのリンク
Ota, Masao
http://soar-rd.shinshu-u.ac.jp/profile/ja.ZefVOFkh.html
出版者
出版者 PUBLIC LIBRARY SCIENCE
引用
内容記述タイプ Other
内容記述 PLOS ONE. 7(12):e50566 (2012)
書誌情報 PLOS ONE

巻 7, 号 12, 発行日 2012-12-05
抄録
内容記述タイプ Abstract
内容記述 Sherpas comprise a population of Tibetan ancestry in the Himalayan region that is renowned for its mountaineering prowess. The very small amount of available genetic information for Sherpas is insufficient to explain their physiological ability to adapt to high-altitude hypoxia. Recent genetic evidence has indicated that natural selection on the endothelial PAS domain protein 1 (EPAS1) gene was occurred in the Tibetan population during their occupation in the Tibetan Plateau for millennia. Tibetan-specific variations in EPAS1 may regulate the physiological responses to high-altitude hypoxia via a hypoxia-inducible transcription factor pathway. We examined three significant tag single-nucleotide polymorphisms (SNPs, rs13419896, rs4953354, and rs4953388) in the EPAS1 gene in Sherpas, and compared these variants with Tibetan highlanders on the Tibetan Plateau as well as with non-Sherpa lowlanders. We found that Sherpas and Tibetans on the Tibetan Plateau exhibit similar patterns in three EPAS1 significant tag SNPs, but these patterns are the reverse of those in non-Sherpa lowlanders. The three SNPs were in strong linkage in Sherpas, but in weak linkage in non-Sherpas. Importantly, the haplotype structured by the Sherpa-dominant alleles was present in Sherpas but rarely present in non-Sherpas. Surprisingly, the average level of serum erythropoietin in Sherpas at 3440 m was equal to that in non-Sherpas at 1300 m, indicating a resistant response of erythropoietin to high-altitude hypoxia in Sherpas. These observations strongly suggest that EPAS1 is under selection for adaptation to the high-altitude life of Tibetan populations, including Sherpas. Understanding of the mechanism of hypoxia tolerance in Tibetans is expected to provide lights to the therapeutic solutions of some hypoxia-related human diseases, such as cardiovascular disease and cancer.
資源タイプ(コンテンツの種類)
内容記述タイプ Other
内容記述 Article
ISSN
収録物識別子タイプ ISSN
収録物識別子 1932-6203
PubMed
関連識別子
識別子タイプ PMID
関連識別子 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=23227185
関連名称
関連名称 23227185
DOI
関連識別子
識別子タイプ DOI
関連識別子 http://dx.doi.org/10.1371/journal.pone.0050566
関連名称
関連名称 10.1371/journal.pone.0050566
権利
権利情報 Copyright© 2012 Hanaoka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
著者版フラグ
値 publisher
WoS
Web of Science
http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000312588200045
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