Co-Regulated Transcriptional Networks Contribute to Natural Genetic Contribute Variation in Drosophila Sleep

Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA.
Nature Genetics (Impact Factor: 29.35). 04/2009; 41(3):371-5. DOI: 10.1038/ng.330
Source: PubMed


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.

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Available from: Julien F Ayroles, Jul 09, 2014
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    • "Modulated modularity clustering analysis: An analysis to determine coexpressed genes to identify possibly functionally relevant biological modules was performed with modulated modularity clustering (Stone and Ayroles 2009) on sets of genes filtered by statistical correlation with a biological factor of interest (e.g., genes with significant genotype-by-diet interactions or those highly correlated with weight). Genes were filtered at a correlation significance level of P , 0.01 (Harbison et al. 2009) unless otherwise noted. The gene lists identified as occupying correlated Figure 1 Transcripts and metabolites significant for genetic, dietary, and genotype-by-diet interaction effects. "
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    • "Jumbo-Lucioni et al., 2010). Analysis of quantitative trait transcripts for sleep duration identified Akt1, which regulates metabolic function and insulin–TOR signaling (Harbison et al., 2009; Kockel et al., 2010 "
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    • "We would generally expect an increase in variance at each successive physiological level such that the strength of genetic association decreases from transcript to metabolite to phenotype. This model has been used to support the notion that modules of gene activity, for example, may often associate with complex traits (Ayroles et al. 2009; Harbison et al. 2009). However, evidence that contradicts this model, and even suggests that modular reorganization may occur at successive levels of molecular function, is beginning to appear, considerably complicating the mapping of genotype to phenotype. "
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