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PLoS Biol. 2018 Aug 9;16(8):e2005750. doi: 10.1371/journal.pbio.2005750. eCollection 2018 Aug.

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

Author information

1
Center for Integrative Genomics, University of Lausanne, Switzerland.
2
Vital-IT Systems Biology Division, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
3
Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.

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.

Comment in

PMID:
30091978
PMCID:
PMC6085075
DOI:
10.1371/journal.pbio.2005750
[Indexed for MEDLINE]
Free PMC Article

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