|Title||Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep.|
|Publication Type||Journal Article|
|Year of Publication||2009|
|Authors||Harbison, ST, Carbone, MAnna, Ayroles, JF, Stone, EA, Lyman, RF, Mackay, TFC|
|Date Published||2009 Mar|
|Keywords||Animals, Animals, Genetically Modified, Animals, Inbred Strains, Drosophila, Drosophila Proteins, Female, Gene Expression Regulation, Gene Regulatory Networks, Genes, Insect, Genetic Variation, Genome, Insect, Genome-Wide Association Study, Male, Models, Biological, Molecular Sequence Data, Polymorphism, Genetic, Sleep|
Sleep disorders are common in humans, and sleep loss increases the risk of obesity and diabetes. Studies in Drosophila have revealed molecular pathways and neural tissues 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 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.
|Alternate Journal||Nat. Genet.|