Genome-Wide Association for Sensitivity to Chronic Oxidative Stress in Drosophila melanogaster

Reactive oxygen species (ROS) are a common byproduct of mitochondrial energy metabolism, and can also be induced by exogenous sources, including UV light, radiation, and environmental toxins. ROS generation is essential for maintaining homeostasis by triggering cellular signaling pathways and host d...

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Main Authors:	Jordan, Katherine W., Craver, Kyle L., Magwire, Michael M., Cubilla, Carmen E., Mackay, Trudy F. C., Anholt, Robert R. H.
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371005/

id	pubmed-3371005
recordtype	oai_dc
spelling	pubmed-33710052012-06-19 Genome-Wide Association for Sensitivity to Chronic Oxidative Stress in Drosophila melanogaster Jordan, Katherine W. Craver, Kyle L. Magwire, Michael M. Cubilla, Carmen E. Mackay, Trudy F. C. Anholt, Robert R. H. Research Article Reactive oxygen species (ROS) are a common byproduct of mitochondrial energy metabolism, and can also be induced by exogenous sources, including UV light, radiation, and environmental toxins. ROS generation is essential for maintaining homeostasis by triggering cellular signaling pathways and host defense mechanisms. However, an imbalance of ROS induces oxidative stress and cellular death and is associated with human disease, including age-related locomotor impairment. To identify genes affecting sensitivity and resistance to ROS-induced locomotor decline, we assessed locomotion of aged flies of the sequenced, wild-derived lines from the Drosophila melanogaster Genetics Reference Panel on standard medium and following chronic exposure to medium supplemented with 3 mM menadione sodium bisulfite (MSB). We found substantial genetic variation in sensitivity to oxidative stress with respect to locomotor phenotypes. We performed genome-wide association analyses to identify candidate genes associated with variation in sensitivity to ROS-induced decline in locomotor performance, and confirmed the effects for 13 of 16 mutations tested in these candidate genes. Candidate genes associated with variation in sensitivity to MSB-induced oxidative stress form networks of genes involved in neural development, immunity, and signal transduction. Many of these genes have human orthologs, highlighting the utility of genome-wide association in Drosophila for studying complex human disease. Public Library of Science 2012-06-08 /pmc/articles/PMC3371005/ /pubmed/22715409 http://dx.doi.org/10.1371/journal.pone.0038722 Text en Jordan et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Jordan, Katherine W. Craver, Kyle L. Magwire, Michael M. Cubilla, Carmen E. Mackay, Trudy F. C. Anholt, Robert R. H.
spellingShingle	Jordan, Katherine W. Craver, Kyle L. Magwire, Michael M. Cubilla, Carmen E. Mackay, Trudy F. C. Anholt, Robert R. H. Genome-Wide Association for Sensitivity to Chronic Oxidative Stress in Drosophila melanogaster
author_facet	Jordan, Katherine W. Craver, Kyle L. Magwire, Michael M. Cubilla, Carmen E. Mackay, Trudy F. C. Anholt, Robert R. H.
author_sort	Jordan, Katherine W.
title	Genome-Wide Association for Sensitivity to Chronic Oxidative Stress in Drosophila melanogaster
title_short	Genome-Wide Association for Sensitivity to Chronic Oxidative Stress in Drosophila melanogaster
title_full	Genome-Wide Association for Sensitivity to Chronic Oxidative Stress in Drosophila melanogaster
title_fullStr	Genome-Wide Association for Sensitivity to Chronic Oxidative Stress in Drosophila melanogaster
title_full_unstemmed	Genome-Wide Association for Sensitivity to Chronic Oxidative Stress in Drosophila melanogaster
title_sort	genome-wide association for sensitivity to chronic oxidative stress in drosophila melanogaster
description	Reactive oxygen species (ROS) are a common byproduct of mitochondrial energy metabolism, and can also be induced by exogenous sources, including UV light, radiation, and environmental toxins. ROS generation is essential for maintaining homeostasis by triggering cellular signaling pathways and host defense mechanisms. However, an imbalance of ROS induces oxidative stress and cellular death and is associated with human disease, including age-related locomotor impairment. To identify genes affecting sensitivity and resistance to ROS-induced locomotor decline, we assessed locomotion of aged flies of the sequenced, wild-derived lines from the Drosophila melanogaster Genetics Reference Panel on standard medium and following chronic exposure to medium supplemented with 3 mM menadione sodium bisulfite (MSB). We found substantial genetic variation in sensitivity to oxidative stress with respect to locomotor phenotypes. We performed genome-wide association analyses to identify candidate genes associated with variation in sensitivity to ROS-induced decline in locomotor performance, and confirmed the effects for 13 of 16 mutations tested in these candidate genes. Candidate genes associated with variation in sensitivity to MSB-induced oxidative stress form networks of genes involved in neural development, immunity, and signal transduction. Many of these genes have human orthologs, highlighting the utility of genome-wide association in Drosophila for studying complex human disease.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371005/
_version_	1611535467327520768

Genome-Wide Association for Sensitivity to Chronic Oxidative Stress in Drosophila melanogaster

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