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Identification of the genetic factors contributing to human adaptation to these conditions enhances our understanding of the underlying molecular and physiological mechanisms. In our study, we analyzed the exomes of 22 high altitude mountaineers to uncover genetic variants contributing to hypoxic adaptation. To our surprise, we identified two putative loss\u2010of\u2010function variants, rs1385101139 in <jats:italic>RTEL1<\/jats:italic> and rs1002726737 in <jats:italic>COL6A1<\/jats:italic> in two extremely high altitude (personal record of more than 8500\u2009m) professional climbers. Both variants can be interpreted as pathogenic according to medical geneticists' guidelines, and are linked to inherited conditions involving respiratory failure (late\u2010onset pulmonary fibrosis and severe Ullrich muscular dystrophy for rs1385101139 and rs1002726737, respectively). Our results suggest that a loss of gene function may act as an important factor of human adaptation, which is corroborated by previous reports in other human subjects.<\/jats:p>","DOI":"10.14814\/phy2.16015","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T01:44:51Z","timestamp":1713923091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exome sequencing in extreme altitude mountaineers identifies pathogenic variants in <i>RTEL1<\/i> and <i>COL6A1<\/i> previously associated with respiratory failure"],"prefix":"10.14814","volume":"12","author":[{"given":"Evgeniia M.","family":"Maksiutenko","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine D.O. 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St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7465-4504","authenticated-orcid":false,"given":"Andrey S.","family":"Glotov","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine D.O. Ott Research Institute of Obstetrics, Gynaecology, and Reproductology  St. Petersburg Russia"},{"name":"Department of Genetics and Biotechnology St. Petersburg State University  St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg S.","family":"Glotov","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine D.O. 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