Article (Scientific journals)
Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population.
Wu, Yibo; Williams, Evan; Dubuis, Sebastien et al.
2014In Cell, 158 (6), p. 1415-1430
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Keywords :
Animals; Gene Expression Profiling; Glucose/metabolism; Humans; Ketone Oxidoreductases/metabolism; Liver/chemistry/cytology/metabolism; Mice/classification/genetics/metabolism; Mice, Inbred C57BL; Mice, Inbred DBA; Mitochondria/chemistry/metabolism; Proteome/analysis; Quantitative Trait Loci; Serum/chemistry/metabolism; Unfolded Protein Response
Abstract :
[en] The manner by which genotype and environment affect complex phenotypes is one of the fundamental questions in biology. In this study, we quantified the transcriptome--a subset of the metabolome--and, using targeted proteomics, quantified a subset of the liver proteome from 40 strains of the BXD mouse genetic reference population on two diverse diets. We discovered dozens of transcript, protein, and metabolite QTLs, several of which linked to metabolic phenotypes. Most prominently, Dhtkd1 was identified as a primary regulator of 2-aminoadipate, explaining variance in fasted glucose and diabetes status in both mice and humans. These integrated molecular profiles also allowed further characterization of complex pathways, particularly the mitochondrial unfolded protein response (UPR(mt)). UPR(mt) shows strikingly variant responses at the transcript and protein level that are remarkably conserved among C. elegans, mice, and humans. Overall, these examples demonstrate the value of an integrated multilayered omics approach to characterize complex metabolic phenotypes.
Disciplines :
Genetics & genetic processes
Author, co-author :
Wu, Yibo
Williams, Evan  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Dubuis, Sebastien
Mottis, Adrienne
Jovaisaite, Virginija
Houten, Sander M.
Argmann, Carmen A.
Faridi, Pouya
Wolski, Witold
Kutalik, Zoltan
Zamboni, Nicola
Auwerx, Johan
Aebersold, Ruedi
More authors (3 more) Less
External co-authors :
yes
Language :
English
Title :
Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population.
Publication date :
2014
Journal title :
Cell
ISSN :
1097-4172
Publisher :
Cell Press, United States - Massachusetts
Volume :
158
Issue :
6
Pages :
1415-1430
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2014 Elsevier Inc. All rights reserved.
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