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Identification of genetic elements in metabolism by high-throughput mouse phenotyping
J. Rozman, B. Rathkolb, MA. Oestereicher, C. Schütt, AC. Ravindranath, S. Leuchtenberger, S. Sharma, M. Kistler, M. Willershäuser, R. Brommage, TF. Meehan, J. Mason, H. Haselimashhadi, . , T. Hough, AM. Mallon, S. Wells, L. Santos, CJ. Lelliott,...
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Perzistentní odkaz
https://www.medvik.cz/link/bmc19000975
Online
Plný text
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- MeSH
- bazální metabolismus genetika MeSH
- celogenomová asociační studie MeSH
- diabetes mellitus 2. typu genetika MeSH
- fenotyp MeSH
- genové regulační sítě MeSH
- krevní glukóza metabolismus MeSH
- lidé MeSH
- metabolické nemoci genetika MeSH
- myši knockoutované MeSH
- myši MeSH
- obezita genetika MeSH
- plocha pod křivkou MeSH
- rychlé screeningové testy MeSH
- spotřeba kyslíku genetika MeSH
- tělesná hmotnost genetika MeSH
- triglyceridy metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.
Children's Hospital Oakland Research Institute 5700 Martin Luther King Jr Way Oakland CA 94609 USA
Medical Research Council Harwell Oxfordshire OX11 0RD UK
Mouse Biology Program University of California One Shields Avenue Davis CA 95616 USA
RIKEN BioResource Center 3 1 1 Koyadai Tsukuba Ibaraki 305 0074 Japan
The Jackson Laboratory 600 Main Street Bar Harbor ME 04609 USA
The Wellcome Trust Sanger Institute Wellcome Genome Campus Hinxton Cambridge CB10 1SA UK
Citace poskytuje Crossref.org
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- $a Rozman, Jan $u German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany. German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
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