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Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas
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 evide...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515610/ https://www.ncbi.nlm.nih.gov/pubmed/23227185 http://dx.doi.org/10.1371/journal.pone.0050566 |
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author | Hanaoka, Masayuki Droma, Yunden Basnyat, Buddha Ito, Michiko Kobayashi, Nobumitsu Katsuyama, Yoshihiko Kubo, Keishi Ota, Masao |
author_facet | Hanaoka, Masayuki Droma, Yunden Basnyat, Buddha Ito, Michiko Kobayashi, Nobumitsu Katsuyama, Yoshihiko Kubo, Keishi Ota, Masao |
author_sort | Hanaoka, Masayuki |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3515610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35156102012-12-07 Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas Hanaoka, Masayuki Droma, Yunden Basnyat, Buddha Ito, Michiko Kobayashi, Nobumitsu Katsuyama, Yoshihiko Kubo, Keishi Ota, Masao PLoS One Research Article 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. Public Library of Science 2012-12-05 /pmc/articles/PMC3515610/ /pubmed/23227185 http://dx.doi.org/10.1371/journal.pone.0050566 Text en © 2012 Hanaoka et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Hanaoka, Masayuki Droma, Yunden Basnyat, Buddha Ito, Michiko Kobayashi, Nobumitsu Katsuyama, Yoshihiko Kubo, Keishi Ota, Masao Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas |
title | Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas |
title_full | Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas |
title_fullStr | Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas |
title_full_unstemmed | Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas |
title_short | Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas |
title_sort | genetic variants in epas1 contribute to adaptation to high-altitude hypoxia in sherpas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515610/ https://www.ncbi.nlm.nih.gov/pubmed/23227185 http://dx.doi.org/10.1371/journal.pone.0050566 |
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