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Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density

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Item Type:Article
Title:Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density
Creators Name:Swan, A.L. and Schütt, C. and Rozman, J. and Del Mar Muñiz Moreno, M. and Brandmaier, S. and Simon, M. and Leuchtenberger, S. and Griffiths, M. and Brommage, R. and Keskivali-Bond, P. and Grallert, H. and Werner, T. and Teperino, R. and Becker, L. and Miller, G. and Moshiri, A. and Seavitt, J.R. and Cissell, D.D. and Meehan, T.F. and Acar, E.F. and Lelliott, C.J. and Flenniken, A.M. and Champy, M.F. and Sorg, T. and Ayadi, A. and Braun, R.E. and Cater, H. and Dickinson, M.E. and Flicek, P. and Gallegos, J. and Ghirardello, E.J. and Heaney, J.D. and Jacquot, S. and Lally, C. and Logan, J.G. and Teboul, L. and Mason, J. and Spielmann, N. and McKerlie, C. and Murray, S.A. and Nutter, L.M.J. and Odfalk, K.F. and Parkinson, H. and Prochazka, J. and Reynolds, C.L. and Selloum, M. and Spoutil, F. and Svenson, K.L. and Vales, T.S. and Wells, S.E. and White, J.K. and Sedlacek, R. and Wurst, W. and Lloyd, K.K.C. and Croucher, P.I. and Fuchs, H. and Williams, G.R. and Bassett, D. and Gailus-Durner, V. and Herault, Y. and Mallon, A.M. and Brown, S.D.M. and Mayer-Kuckuk, P. and Hrabe de Angelis, M.
Abstract:The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.
Keywords:Bone Density, Gene Expression Regulation, Gene Ontology, Genetic Pleiotropy, Genetic Promoter Regions, Genome-Wide Association Study, Genotype, Mutation, Osteoblasts, Osteoclasts, Osteoporosis, Phenotype, Protein Interaction Maps, Sex Characteristics, Transcriptome, Transgenic Mice, Animals, Mice
Source:PLoS Genetics
Publisher:Public Library of Science
Page Range:e1009190
Date:28 December 2020
Additional Information:Ralf Kühn is a member of the IMPC Consortium.
Official Publication:https://doi.org/10.1371/journal.pgen.1009190
PubMed:View item in PubMed

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