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Open AccessArticle

Dissecting the Genetic Basis of Variation in Drosophila Sleep Using a Multiparental QTL Mapping Resource

1
Department of Molecular Biosciences, 4043 Haworth Hall, 1200 Sunnyside Avenue, University of Kansas, Lawrence, KS 66045, USA
2
Center for Computational Biology, University of Kansas, Lawrence, KS 66047, USA
*
Author to whom correspondence should be addressed.
Genes 2020, 11(3), 294; https://doi.org/10.3390/genes11030294
Received: 31 January 2020 / Revised: 7 March 2020 / Accepted: 9 March 2020 / Published: 11 March 2020
(This article belongs to the Special Issue Genetic Basis of Phenotypic Variation in Drosophila and Other Insects)
There is considerable variation in sleep duration, timing and quality in human populations, and sleep dysregulation has been implicated as a risk factor for a range of health problems. Human sleep traits are known to be regulated by genetic factors, but also by an array of environmental and social factors. These uncontrolled, non-genetic effects complicate powerful identification of the loci contributing to sleep directly in humans. The model system, Drosophila melanogaster, exhibits a behavior that shows the hallmarks of mammalian sleep, and here we use a multitiered approach, encompassing high-resolution QTL mapping, expression QTL data, and functional validation with RNAi to investigate the genetic basis of sleep under highly controlled environmental conditions. We measured a battery of sleep phenotypes in >750 genotypes derived from a multiparental mapping panel and identified several, modest-effect QTL contributing to natural variation for sleep. Merging sleep QTL data with a large head transcriptome eQTL mapping dataset from the same population allowed us to refine the list of plausible candidate causative sleep loci. This set includes genes with previously characterized effects on sleep and circadian rhythms, in addition to novel candidates. Finally, we employed adult, nervous system-specific RNAi on the Dopa decarboxylase, dyschronic, and timeless genes, finding significant effects on sleep phenotypes for all three. The genes we resolve are strong candidates to harbor causative, regulatory variation contributing to sleep. View Full-Text
Keywords: sleep; activity; Drosophila; DSPR; MPP; QTL; expression QTL sleep; activity; Drosophila; DSPR; MPP; QTL; expression QTL
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    Doi: https://doi.org/10.5061/dryad.6wwpzgmv8
    Link: https://doi.org/10.5061/dryad.6wwpzgmv8
    Description: There are supplementary files to be associated with the manuscript (these are in the *.zip file I uploaded.) In addition, we have made a Dryad data repository (https://doi.org/10.5061/dryad.6wwpzgmv8) and this contains all the raw data associated with the manuscript.
MDPI and ACS Style

R. Smith, B.; J. Macdonald, S. Dissecting the Genetic Basis of Variation in Drosophila Sleep Using a Multiparental QTL Mapping Resource. Genes 2020, 11, 294.

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