Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.

<h4>Background</h4>Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal syst...

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Autores principales:	Allison L Weber, George F Khan, Michael M Magwire, Crystal L Tabor, Trudy F C Mackay, Robert R H Anholt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0328e7ed4f6a4042908e5be7053e3afe
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spelling	oai:doaj.org-article:0328e7ed4f6a4042908e5be7053e3afe2021-11-18T07:23:12ZGenome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.1932-620310.1371/journal.pone.0034745https://doaj.org/article/0328e7ed4f6a4042908e5be7053e3afe2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496853/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress.<h4>Methods and findings</h4>We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genome-wide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67-79% and 56-66% of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis.<h4>Conclusions</h4>We identified novel candidate genes associated with variation in resistance to oxidative stress that have context-dependent effects. These results form the basis for future translational studies to identify oxidative stress susceptibility/resistance genes that are evolutionary conserved and might play a role in human disease.Allison L WeberGeorge F KhanMichael M MagwireCrystal L TaborTrudy F C MackayRobert R H AnholtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34745 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Allison L Weber George F Khan Michael M Magwire Crystal L Tabor Trudy F C Mackay Robert R H Anholt Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.
description	<h4>Background</h4>Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress.<h4>Methods and findings</h4>We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genome-wide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67-79% and 56-66% of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis.<h4>Conclusions</h4>We identified novel candidate genes associated with variation in resistance to oxidative stress that have context-dependent effects. These results form the basis for future translational studies to identify oxidative stress susceptibility/resistance genes that are evolutionary conserved and might play a role in human disease.
format	article
author	Allison L Weber George F Khan Michael M Magwire Crystal L Tabor Trudy F C Mackay Robert R H Anholt
author_facet	Allison L Weber George F Khan Michael M Magwire Crystal L Tabor Trudy F C Mackay Robert R H Anholt
author_sort	Allison L Weber
title	Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.
title_short	Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.
title_full	Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.
title_fullStr	Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.
title_full_unstemmed	Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.
title_sort	genome-wide association analysis of oxidative stress resistance in drosophila melanogaster.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0328e7ed4f6a4042908e5be7053e3afe
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Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.

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