A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations
Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype da...
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ftpubmed:oai:pubmedcentral.nih.gov:4225582 2023-05-15T14:53:35+02:00 A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations Clemente, Florian J. Cardona, Alexia Inchley, Charlotte E. Peter, Benjamin M. Jacobs, Guy Pagani, Luca Lawson, Daniel J. Antão, Tiago Vicente, Mário Mitt, Mario DeGiorgio, Michael Faltyskova, Zuzana Xue, Yali Ayub, Qasim Szpak, Michal Mägi, Reedik Eriksson, Anders Manica, Andrea Raghavan, Maanasa Rasmussen, Morten Rasmussen, Simon Willerslev, Eske Vidal-Puig, Antonio Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Metspalu, Mait Malyarchuk, Boris Derenko, Miroslava Kivisild, Toomas 2014-11-06 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225582/ http://www.ncbi.nlm.nih.gov/pubmed/25449608 https://doi.org/10.1016/j.ajhg.2014.09.016 en eng Elsevier http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225582/ http://www.ncbi.nlm.nih.gov/pubmed/25449608 http://dx.doi.org/10.1016/j.ajhg.2014.09.016 © 2014 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved. Report Text 2014 ftpubmed https://doi.org/10.1016/j.ajhg.2014.09.016 2015-05-09T23:58:32Z Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation. Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6–23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment. Text Arctic Greenland inuits PubMed Central (PMC) Arctic Greenland The American Journal of Human Genetics 95 5 584 589 |
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Report Clemente, Florian J. Cardona, Alexia Inchley, Charlotte E. Peter, Benjamin M. Jacobs, Guy Pagani, Luca Lawson, Daniel J. Antão, Tiago Vicente, Mário Mitt, Mario DeGiorgio, Michael Faltyskova, Zuzana Xue, Yali Ayub, Qasim Szpak, Michal Mägi, Reedik Eriksson, Anders Manica, Andrea Raghavan, Maanasa Rasmussen, Morten Rasmussen, Simon Willerslev, Eske Vidal-Puig, Antonio Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Metspalu, Mait Malyarchuk, Boris Derenko, Miroslava Kivisild, Toomas A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
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Report |
description |
Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation. Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6–23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment. |
format |
Text |
author |
Clemente, Florian J. Cardona, Alexia Inchley, Charlotte E. Peter, Benjamin M. Jacobs, Guy Pagani, Luca Lawson, Daniel J. Antão, Tiago Vicente, Mário Mitt, Mario DeGiorgio, Michael Faltyskova, Zuzana Xue, Yali Ayub, Qasim Szpak, Michal Mägi, Reedik Eriksson, Anders Manica, Andrea Raghavan, Maanasa Rasmussen, Morten Rasmussen, Simon Willerslev, Eske Vidal-Puig, Antonio Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Metspalu, Mait Malyarchuk, Boris Derenko, Miroslava Kivisild, Toomas |
author_facet |
Clemente, Florian J. Cardona, Alexia Inchley, Charlotte E. Peter, Benjamin M. Jacobs, Guy Pagani, Luca Lawson, Daniel J. Antão, Tiago Vicente, Mário Mitt, Mario DeGiorgio, Michael Faltyskova, Zuzana Xue, Yali Ayub, Qasim Szpak, Michal Mägi, Reedik Eriksson, Anders Manica, Andrea Raghavan, Maanasa Rasmussen, Morten Rasmussen, Simon Willerslev, Eske Vidal-Puig, Antonio Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Metspalu, Mait Malyarchuk, Boris Derenko, Miroslava Kivisild, Toomas |
author_sort |
Clemente, Florian J. |
title |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_short |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_full |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_fullStr |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_full_unstemmed |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_sort |
selective sweep on a deleterious mutation in cpt1a in arctic populations |
publisher |
Elsevier |
publishDate |
2014 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225582/ http://www.ncbi.nlm.nih.gov/pubmed/25449608 https://doi.org/10.1016/j.ajhg.2014.09.016 |
geographic |
Arctic Greenland |
geographic_facet |
Arctic Greenland |
genre |
Arctic Greenland inuits |
genre_facet |
Arctic Greenland inuits |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225582/ http://www.ncbi.nlm.nih.gov/pubmed/25449608 http://dx.doi.org/10.1016/j.ajhg.2014.09.016 |
op_rights |
© 2014 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved. |
op_doi |
https://doi.org/10.1016/j.ajhg.2014.09.016 |
container_title |
The American Journal of Human Genetics |
container_volume |
95 |
container_issue |
5 |
container_start_page |
584 |
op_container_end_page |
589 |
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1766325183972376576 |