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...
Published in: | The American Journal of Human Genetics |
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2014
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Online Access: | https://escholarship.org/uc/item/3qj4h08s https://escholarship.org/content/qt3qj4h08s/qt3qj4h08s.pdf https://doi.org/10.1016/j.ajhg.2014.09.016 |
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ftcdlib:oai:escholarship.org:ark:/13030/qt3qj4h08s 2024-09-15T18:09:58+00:00 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 584 - 589 2014-11-01 application/pdf https://escholarship.org/uc/item/3qj4h08s https://escholarship.org/content/qt3qj4h08s/qt3qj4h08s.pdf https://doi.org/10.1016/j.ajhg.2014.09.016 unknown eScholarship, University of California qt3qj4h08s https://escholarship.org/uc/item/3qj4h08s https://escholarship.org/content/qt3qj4h08s/qt3qj4h08s.pdf doi:10.1016/j.ajhg.2014.09.016 CC-BY-NC-ND American journal of human genetics, vol 95, iss 5 Genetics Human Genome Biological Sciences Medical and Health Sciences Genetics & Heredity article 2014 ftcdlib https://doi.org/10.1016/j.ajhg.2014.09.016 2024-06-28T06:28:21Z 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 79protein-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 sweephas 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. Article in Journal/Newspaper Greenland inuits University of California: eScholarship The American Journal of Human Genetics 95 5 584 589 |
institution |
Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Genetics Human Genome Biological Sciences Medical and Health Sciences Genetics & Heredity |
spellingShingle |
Genetics Human Genome Biological Sciences Medical and Health Sciences Genetics & Heredity 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. |
topic_facet |
Genetics Human Genome Biological Sciences Medical and Health Sciences Genetics & Heredity |
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 79protein-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 sweephas 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 |
Article in Journal/Newspaper |
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 |
eScholarship, University of California |
publishDate |
2014 |
url |
https://escholarship.org/uc/item/3qj4h08s https://escholarship.org/content/qt3qj4h08s/qt3qj4h08s.pdf https://doi.org/10.1016/j.ajhg.2014.09.016 |
op_coverage |
584 - 589 |
genre |
Greenland inuits |
genre_facet |
Greenland inuits |
op_source |
American journal of human genetics, vol 95, iss 5 |
op_relation |
qt3qj4h08s https://escholarship.org/uc/item/3qj4h08s https://escholarship.org/content/qt3qj4h08s/qt3qj4h08s.pdf doi:10.1016/j.ajhg.2014.09.016 |
op_rights |
CC-BY-NC-ND |
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 |
_version_ |
1810447579396177920 |