Exome sequencing in extreme altitude mountaineers identifies pathogenic variants in RTEL1 and COL6A1 previously associated with respiratory failure.

Autor: Maksiutenko EM; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynaecology, and Reproductology, St. Petersburg, Russia., Merkureva V; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynaecology, and Reproductology, St. Petersburg, Russia.; CerbaLab Ltd., St. Petersburg, Russia., Barbitoff YA; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynaecology, and Reproductology, St. Petersburg, Russia.; Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg, Russia., Tsay VV; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynaecology, and Reproductology, St. Petersburg, Russia.; CerbaLab Ltd., St. Petersburg, Russia.; Department of Experimental Medical Virology, Molecular Genetics and Biobanking of Pediatric Research and Clinical Center for Infectious Diseases, St. Petersburg, Russia., Aseev MV; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynaecology, and Reproductology, St. Petersburg, Russia.; CerbaLab Ltd., St. Petersburg, Russia., Glotov AS; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynaecology, and Reproductology, St. Petersburg, Russia.; Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg, Russia., Glotov OS; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynaecology, and Reproductology, St. Petersburg, Russia.; Department of Experimental Medical Virology, Molecular Genetics and Biobanking of Pediatric Research and Clinical Center for Infectious Diseases, St. Petersburg, Russia.
Jazyk: angličtina
Zdroj: Physiological reports [Physiol Rep] 2024 Apr; Vol. 12 (8), pp. e16015.
DOI: 10.14814/phy2.16015
Abstrakt: Adaptation of humans to challenging environmental conditions, such as extreme temperature, malnutrition, or hypoxia, is an interesting phenomenon for both basic and applied research. 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-of-function variants, rs1385101139 in RTEL1 and rs1002726737 in COL6A1 in two extremely high altitude (personal record of more than 8500 m) professional climbers. Both variants can be interpreted as pathogenic according to medical geneticists' guidelines, and are linked to inherited conditions involving respiratory failure (late-onset 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.
(© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
Databáze: MEDLINE
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