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Rozman, J. ; Rathkolb, B. ; Oestereicher, M.A. ; Schütt, C. ; Ravindranath, A.C. ; Leuchtenberger, S. ; Sharma, S. ; Kistler, M. ; Willershäuser, M.* ; Brommage, R. ; Meehan, T.F.* ; Mason, J.* ; Haselimashhadi, H.* ; Hough, T.* ; Mallon, A.-M.* ; Wells, S.* ; Santos, L.* ; Lelliott, C.J.* ; White, J.K.* ; Sorg, T.* ; Champy, M.-F.* ; Bower, L.R.* ; Reynolds, C.L.* ; Flenniken, A.M.* ; Murray, S.A.* ; Nutter, L.M.J.* ; Svenson, K.L.* ; West, D.* ; Tocchini-Valentini, G.P.* ; Beaudet, A.L.* ; Bosch, F.* ; Braun, R.B.* ; Dobbie, M.S.* ; Gao, X.* ; Herault, Y.* ; Moshiri, A.* ; Moore, B.A.* ; Kent Lloyd, K.C.* ; McKerlie, C.* ; Masuya, H.* ; Tanaka, N.* ; Flicek, P.* ; Parkinson, H.E.* ; Sedlacek, R.* ; Seong, J.K.* ; Wang, C.-K.L.* ; Moore, M.* ; Brown, S.D.* ; Tschöp, M.H. ; Wurst, W. ; Klingenspor, M.* ; Wolf, E.* ; Beckers, J. ; Machicao, F.* ; Peter, A. ; Staiger, H. ; Häring, H.-U. ; Grallert, H. ; Campillos, M. ; Maier, H. ; Fuchs, H. ; Gailus-Durner, V. ; Werner, T.* ; Hrabě de Angelis, M. ; IMPC Consortium (Eickelberg, O.) ; IMPC Consortium (Yildirim, A.Ö.)

Identification of genetic elements in metabolism by high-throughput mouse phenotyping.  

Nat. Commun. 9:288 (2018)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Insulin-resistance; Diabetes-mellitus; Glycemic Traits; Variants; Architecture; Association; Consortium; Pathways; Disease; Biology
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 288 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Institute of Epidemiology (EPI)
Institute of Diabetes and Obesity (IDO)
Institute of Developmental Genetics (IDG)
Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Bioinformatics and Systems Biology (IBIS)
Institute of Lung Health and Immunity (LHI)
Research Unit Signaling and Translation (SAT)
POF Topic(s) 30201 - Metabolic Health
30202 - Environmental Health
90000 - German Center for Diabetes Research
30204 - Cell Programming and Repair
30505 - New Technologies for Biomedical Discoveries
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Genetics and Epidemiology
Helmholtz Diabetes Center
Enabling and Novel Technologies
Lung Research
PSP-Element(e) G-500600-001
G-500692-001
G-504091-002
G-501900-063
G-502200-001
G-500500-001
G-500600-004
G-502400-001
G-551700-002
G-501600-001
G-505000-007
G-505000-001
G-500500-002
G-501900-022
G-501900-402
G-509800-002
DOI 10.1038/s41467-017-01995-2
WOS ID WOS:000422745800023
Scopus ID 85040788526
PubMed ID 29348434
Erfassungsdatum 2018-03-05
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