{"_buckets": {"deposit": "5bc14e6f-a830-4242-a9c7-65b5d0a2cec0"}, "_deposit": {"id": "3753", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "3753"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00003753"}, "item_6_biblio_info_6": {"attribute_name": "\u66f8\u8a8c\u60c5\u5831", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2012-12-05", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "12", "bibliographicVolumeNumber": "7", "bibliographic_titles": [{"bibliographic_title": "PLOS ONE"}]}]}, "item_6_description_20": {"attribute_name": "\u6284\u9332", "attribute_value_mlt": [{"subitem_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.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "\u8cc7\u6e90\u30bf\u30a4\u30d7\uff08\u30b3\u30f3\u30c6\u30f3\u30c4\u306e\u7a2e\u985e\uff09", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "\u5f15\u7528", "attribute_value_mlt": [{"subitem_description": "PLOS ONE. 7(12):e50566 (2012)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "\u4fe1\u5dde\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7\u3078\u306e\u30ea\u30f3\u30af", "attribute_value_mlt": [{"subitem_link_text": "Hanaoka, Masayuki", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.yCLmHVkh.html"}, {"subitem_link_text": "Ota, Masao", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.ZefVOFkh.html"}]}, "item_6_link_67": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000312588200045"}]}, "item_6_publisher_4": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "PUBLIC LIBRARY SCIENCE"}]}, "item_6_relation_47": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "23227185"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search\u0026DB=pubmed\u0026term=23227185", "subitem_relation_type_select": "PMID"}}]}, "item_6_relation_48": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1371/journal.pone.0050566"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "http://dx.doi.org/10.1371/journal.pone.0050566", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_62": {"attribute_name": "\u6a29\u5229", "attribute_value_mlt": [{"subitem_rights": "Copyright\u00a9 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."}]}, "item_6_select_64": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1932-6203", "subitem_source_identifier_type": "ISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1932-6203", "subitem_source_identifier_type": "ISSN"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "OXIDE SYNTHASE GENE; HEMOGLOBIN CONCENTRATION; TIBETAN HIGHLANDERS; PULMONARY-EDEMA; POLYMORPHISMS; ASSOCIATION; POPULATION; METABOLISM; SELECTION; GLUCOSE"}]}, "item_6_textarea_68": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "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."}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Hanaoka,  Masayuki"}], "nameIdentifiers": [{"nameIdentifier": "6815", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Droma,  Yunden"}], "nameIdentifiers": [{"nameIdentifier": "6816", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Basnyat,  Buddha"}], "nameIdentifiers": [{"nameIdentifier": "6817", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ito,  Michiko"}], "nameIdentifiers": [{"nameIdentifier": "6818", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kobayashi,  Nobumitsu"}], "nameIdentifiers": [{"nameIdentifier": "6819", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Katsuyama,  Yoshihiko"}], "nameIdentifiers": [{"nameIdentifier": "6820", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kubo,  Keishi"}], "nameIdentifiers": [{"nameIdentifier": "6821", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ota,  Masao"}], "nameIdentifiers": [{"nameIdentifier": "6822", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "\u30d5\u30a1\u30a4\u30eb\u60c5\u5831", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2015-09-24"}], "displaytype": "detail", "download_preview_message": "", "filename": "Genetic_Variants_EPAS1_Contribute_Adaptation.pdf", "filesize": [{"value": "311.2 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 3112000, "url": {"label": "Genetic_Variants_EPAS1_Contribute_Adaptation.pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/3753/files/Genetic_Variants_EPAS1_Contribute_Adaptation.pdf"}, "version_id": "85f722c3-c64e-4c1a-a60a-dbe7d49369b7"}]}, "item_language": {"attribute_name": "\u8a00\u8a9e", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "\u8cc7\u6e90\u30bf\u30a4\u30d7", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas", "item_titles": {"attribute_name": "\u30bf\u30a4\u30c8\u30eb", "attribute_value_mlt": [{"subitem_title": "Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas"}]}, "item_type_id": "6", "owner": "1", "path": ["461/462"], "permalink_uri": "http://hdl.handle.net/10091/17571", "pubdate": {"attribute_name": "\u516c\u958b\u65e5", "attribute_name_i18n": "\u516c\u958b\u65e5", "attribute_value": "2014-06-05"}, "publish_date": "2014-06-05", "publish_status": "0", "recid": "3753", "relation": {}, "relation_version_is_last": true, "title": ["Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas"], "weko_shared_id": 3}