Journal
NATURE GENETICS
Volume 41, Issue 3, Pages 371-375Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.330
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Funding
- National Institutes of Health [R01 GM 45146, R01 GM 076083, R01 AA016560]
- National Sleep Foundation
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM045146, R01GM076083] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA016560] Funding Source: NIH RePORTER
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Sleep disorders are common in humans, and sleep loss increases the risk of obesity and diabetes(1). Studies in Drosophila(2,3) have revealed molecular pathways(4-7) and neural tissues(8-10) regulating sleep; however, genes that maintain genetic variation for sleep in natural populations are unknown. Here, we characterized sleep in 40 wild-derived Drosophila lines and observed abundant genetic variation in sleep architecture. We associated sleep with genome-wide variation in gene expression(11) to identify candidate genes. We independently confirmed that molecular polymorphisms in Catsup (Catecholamines up) are associated with variation in sleep and that P-element mutations in four candidate genes affect sleep and gene expression. Transcripts associated with sleep grouped into biologically plausible genetically correlated transcriptional modules. We confirmed co-regulated gene expression using P-element mutants. Quantitative genetic analysis of natural phenotypic variation is an efficient method for revealing candidate genes and pathways.
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