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Identifying positive selection candidate loci for high-altitude adaptation in Andean populations

High-altitude environments (>2,500 m) provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide data...

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Autores principales: Bigham, Abigail W, Mao, Xianyun, Mei, Rui, Brutsaert, Tom, Wilson, Megan J, Julian, Colleen Glyde, Parra, Esteban J, Akey, Joshua M, Moore, Lorna G, Shriver, Mark D
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857381/
https://www.ncbi.nlm.nih.gov/pubmed/20038496
http://dx.doi.org/10.1186/1479-7364-4-2-79
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author Bigham, Abigail W
Mao, Xianyun
Mei, Rui
Brutsaert, Tom
Wilson, Megan J
Julian, Colleen Glyde
Parra, Esteban J
Akey, Joshua M
Moore, Lorna G
Shriver, Mark D
author_facet Bigham, Abigail W
Mao, Xianyun
Mei, Rui
Brutsaert, Tom
Wilson, Megan J
Julian, Colleen Glyde
Parra, Esteban J
Akey, Joshua M
Moore, Lorna G
Shriver, Mark D
author_sort Bigham, Abigail W
collection PubMed
description High-altitude environments (>2,500 m) provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide datasets for signatures of natural selection. In this work, we report on a study to identify selection-nominated candidate genes involved in adaptation to hypoxia in one highland group, Andeans from the South American Altiplano. We analysed dense microarray genotype data using four test statistics that detect departures from neutrality. Using a candidate gene, single nucleotide polymorphism-based approach, we identified genes exhibiting preliminary evidence of recent genetic adaptation in this population. These included genes that are part of the hypoxia-inducible transcription factor (HIF) pathway, a biochemical pathway involved in oxygen homeostasis, as well as three other genomic regions previously not known to be associated with high-altitude phenotypes. In addition to identifying selection-nominated candidate genes, we also tested whether the HIF pathway shows evidence of natural selection. Our results indicate that the genes of this biochemical pathway as a group show no evidence of having evolved in response to hypoxia in Andeans. Results from particular HIF-targeted genes, however, suggest that genes in this pathway could play a role in Andean adaptation to high altitude, even if the pathway as a whole does not show higher relative rates of evolution. These data suggest a genetic role in high-altitude adaptation and provide a basis for genotype/phenotype association studies that are necessary to confirm the role of putative natural selection candidate genes and gene regions in adaptation to altitude.
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spelling pubmed-28573812010-04-20 Identifying positive selection candidate loci for high-altitude adaptation in Andean populations Bigham, Abigail W Mao, Xianyun Mei, Rui Brutsaert, Tom Wilson, Megan J Julian, Colleen Glyde Parra, Esteban J Akey, Joshua M Moore, Lorna G Shriver, Mark D Hum Genomics Primary Research High-altitude environments (>2,500 m) provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide datasets for signatures of natural selection. In this work, we report on a study to identify selection-nominated candidate genes involved in adaptation to hypoxia in one highland group, Andeans from the South American Altiplano. We analysed dense microarray genotype data using four test statistics that detect departures from neutrality. Using a candidate gene, single nucleotide polymorphism-based approach, we identified genes exhibiting preliminary evidence of recent genetic adaptation in this population. These included genes that are part of the hypoxia-inducible transcription factor (HIF) pathway, a biochemical pathway involved in oxygen homeostasis, as well as three other genomic regions previously not known to be associated with high-altitude phenotypes. In addition to identifying selection-nominated candidate genes, we also tested whether the HIF pathway shows evidence of natural selection. Our results indicate that the genes of this biochemical pathway as a group show no evidence of having evolved in response to hypoxia in Andeans. Results from particular HIF-targeted genes, however, suggest that genes in this pathway could play a role in Andean adaptation to high altitude, even if the pathway as a whole does not show higher relative rates of evolution. These data suggest a genetic role in high-altitude adaptation and provide a basis for genotype/phenotype association studies that are necessary to confirm the role of putative natural selection candidate genes and gene regions in adaptation to altitude. BioMed Central 2009-12-01 /pmc/articles/PMC2857381/ /pubmed/20038496 http://dx.doi.org/10.1186/1479-7364-4-2-79 Text en Copyright ©2009 Henry Stewart Publications
spellingShingle Primary Research
Bigham, Abigail W
Mao, Xianyun
Mei, Rui
Brutsaert, Tom
Wilson, Megan J
Julian, Colleen Glyde
Parra, Esteban J
Akey, Joshua M
Moore, Lorna G
Shriver, Mark D
Identifying positive selection candidate loci for high-altitude adaptation in Andean populations
title Identifying positive selection candidate loci for high-altitude adaptation in Andean populations
title_full Identifying positive selection candidate loci for high-altitude adaptation in Andean populations
title_fullStr Identifying positive selection candidate loci for high-altitude adaptation in Andean populations
title_full_unstemmed Identifying positive selection candidate loci for high-altitude adaptation in Andean populations
title_short Identifying positive selection candidate loci for high-altitude adaptation in Andean populations
title_sort identifying positive selection candidate loci for high-altitude adaptation in andean populations
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857381/
https://www.ncbi.nlm.nih.gov/pubmed/20038496
http://dx.doi.org/10.1186/1479-7364-4-2-79
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