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A systems genetics resource and analysis of sleep regulation in the mouse

Diessler, Shanaz, Jan, Maxime, Emmenegger, Yann, Guex, Nicolas, Middleton, Benita, Skene, Debra J., Ibberson, Mark, Burdet, Frederic, Götz, Lou, Pagni, Marco , Sankar, Martial, Liechti, Robin, Hor, Charlotte N., Xenarios, Ioannis and Franken, Paul (2018) A systems genetics resource and analysis of sleep regulation in the mouse PLOS Biology, 16 (8), e2005750. pp. 1-39.

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Abstract

Sleep is essential for optimal brain functioning and health, but the biological substrates through which sleep delivers these beneficial effects remain largely unknown. We used a systems genetics approach in the BXD genetic reference population (GRP) of mice and assembled a comprehensive experimental knowledge base comprising a deep "sleep-wake" phenome, central and peripheral transcriptomes, and plasma metabolome data, collected under undisturbed baseline conditions and after sleep deprivation (SD). We present analytical tools to interactively interrogate the database, visualize the molecular networks altered by sleep loss, and prioritize candidate genes. We found that a one-time, short disruption of sleep already extensively reshaped the systems genetics landscape by altering 60%–78% of the transcriptomes and the metabolome, with numerous genetic loci affecting the magnitude and direction of change. Systems genetics integrative analyses drawing on all levels of organization imply α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and fatty acid turnover as substrates of the negative effects of insufficient sleep. Our analyses demonstrate that genetic heterogeneity and the effects of insufficient sleep itself on the transcriptome and metabolome are far more widespread than previously reported.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Diessler, Shanaz
Jan, Maxime
Emmenegger, Yann
Guex, Nicolas
Middleton, BenitaB.Middleton@surrey.ac.uk
Skene, Debra J.D.Skene@surrey.ac.uk
Ibberson, Mark
Burdet, Frederic
Götz, Lou
Pagni, Marco
Sankar, Martial
Liechti, Robin
Hor, Charlotte N.
Xenarios, Ioannis
Franken, Paul
Date : 9 August 2018
DOI : 10.1371/journal.pbio.2005750
Copyright Disclaimer : Copyright: © 2018 Diessler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Depositing User : Clive Harris
Date Deposited : 14 Aug 2018 08:23
Last Modified : 24 Oct 2018 08:51
URI: http://epubs.surrey.ac.uk/id/eprint/848917

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