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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Autores principales:	Katherine W Jordan, Kyle L Craver, Michael M Magwire, Carmen E Cubilla, 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/d0958e6ff42d40e7994170468552436f
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spelling	oai:doaj.org-article:d0958e6ff42d40e7994170468552436f2021-11-18T07:15:55ZGenome-wide association for sensitivity to chronic oxidative stress in Drosophila melanogaster.1932-620310.1371/journal.pone.0038722https://doaj.org/article/d0958e6ff42d40e7994170468552436f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22715409/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Reactive 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.Katherine W JordanKyle L CraverMichael M MagwireCarmen E CubillaTrudy F C MackayRobert R H AnholtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e38722 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katherine W Jordan Kyle L Craver Michael M Magwire Carmen E Cubilla Trudy F C Mackay Robert R H Anholt 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.
format	article
author	Katherine W Jordan Kyle L Craver Michael M Magwire Carmen E Cubilla Trudy F C Mackay Robert R H Anholt
author_facet	Katherine W Jordan Kyle L Craver Michael M Magwire Carmen E Cubilla Trudy F C Mackay Robert R H Anholt
author_sort	Katherine W Jordan
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.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d0958e6ff42d40e7994170468552436f
work_keys_str_mv	AT katherinewjordan genomewideassociationforsensitivitytochronicoxidativestressindrosophilamelanogaster AT kylelcraver genomewideassociationforsensitivitytochronicoxidativestressindrosophilamelanogaster AT michaelmmagwire genomewideassociationforsensitivitytochronicoxidativestressindrosophilamelanogaster AT carmenecubilla genomewideassociationforsensitivitytochronicoxidativestressindrosophilamelanogaster AT trudyfcmackay genomewideassociationforsensitivitytochronicoxidativestressindrosophilamelanogaster AT robertrhanholt genomewideassociationforsensitivitytochronicoxidativestressindrosophilamelanogaster
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Genome-wide association for sensitivity to chronic oxidative stress in Drosophila melanogaster.

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