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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)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Insulin-resistance; Diabetes-mellitus; Glycemic Traits; Variants; Architecture; Association; Consortium; Pathways; Disease; Biology

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 9, Issue: 1, Article Number: 288

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Experimental Genetics (IEG)
Institute of Epidemiology II (EPI2)
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)
Lung Health and Immunity (LHI)
Institute of Lung Biology (LHI)
Research Unit Signaling and Translation (SAT)