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Joint mouse–human phenome-wide association to test gene function and disease risk
- Source :
- Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016), Nature Communications
- Publication Year :
- 2016
- Publisher :
- Nature Portfolio, 2016.
-
Abstract
- Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ∼5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of ∼4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets—by far the largest coherent phenome for any experimental cohort (www.genenetwork.org). We tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.<br />Phenome-wide association is a novel method that links sequence variants to a spectrum of phenotypes and diseases. Here the authors generate detailed mouse genetic and phenome data which links their phenome-wide association study (PheWAS) of mouse to corresponding PheWAS in human.
- Subjects :
- 0301 basic medicine
Science
Quantitative Trait Loci
General Physics and Astronomy
Genomics
Genome-wide association study
Phenome
Quantitative trait locus
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Fumarate Hydratase
Mice
03 medical and health sciences
Bone Density/genetics
Bone Density
Genetic variation
Animals
Humans
Genetic Predisposition to Disease
Caenorhabditis elegans
Gene
Gene Library
Regulation of gene expression
Genetics
Multidisciplinary
Gene Expression Regulation/physiology
Genetic Variation
General Chemistry
Phenotype
Fumarate Hydratase/genetics/metabolism
030104 developmental biology
Gene Expression Regulation
Mice, Inbred DBA
Genetics & genetic processes [F10] [Life sciences]
Génétique & processus génétiques [F10] [Sciences du vivant]
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....e441e39e3468521968728a2ee56848fe