Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.
Anna L SwanChristine SchüttJan RozmanMaria Del Mar Muñiz-MorenoStefan BrandmaierMichelle SimonStefanie LeuchtenbergerMark GriffithsRobert BrommagePiia Keskivali-BondHarald GrallertThomas WernerRaffaele TeperinoLore BeckerGregor MillerAla MoshiriJohn R SeavittDerek D CissellTerrence F MeehanElif F AcarChristopher J LelliottAnn M FlennikenMarie-France ChampyTania SorgAbdel AyadiRobert E BraunHeather L CaterMary E DickinsonPaul FlicekJuan GallegosElena J GhirardelloJason D HeaneySylvie JacquotConnor LallyJohn G LoganLydia TeboulJeremy C MasonNadine SpielmannColin McKerlieStephen A MurrayLauryl M J NutterKristian F OdfalkHelen ParkinsonJan ProchazkaCorey L ReynoldsMohammed SelloumFrantisek SpoutilKaren L SvensonTaylor S ValesSara E WellsJacqueline K WhiteRadislav SedlacekWolfgang WurstKevin C Kent LloydPeter I CroucherHelmut FuchsGraham R WilliamsJ H Duncan BassettValerie Gailus-DurnerYann HéraultAnn-Marie MallonSteve D M BrownPhilipp Mayer-KuckukMartin Hrabě de Angelisnull nullPublished in: PLoS genetics (2020)
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.
Keyphrases
- bone mineral density
- postmenopausal women
- body composition
- genome wide
- genome wide identification
- bioinformatics analysis
- healthcare
- dna methylation
- endothelial cells
- escherichia coli
- machine learning
- induced apoptosis
- signaling pathway
- risk assessment
- oxidative stress
- electronic health record
- cell proliferation
- social media
- big data
- artificial intelligence
- climate change
- soft tissue
- endoplasmic reticulum stress