IBMS BoneKEy | BoneKEy Watch
Parker et al. GWAS approach in mice investigates genetic basis of complex traits
DOI:10.1038/bonekey.2016.95
In a new approach to genome-wide association studies in mice, Parker et al. chose Carworth Farms White (CFW) mice as their study model. CFW mice show more rapid decay of linkage disequilibrium than other mouse strains and so can help achieve a higher mapping resolution. A total of 1,200 male CFW mice were used to investigate physiological, behavioral and gene expression phenotypes.
Genotypes at 92,734 distinct single nucleotide polymorphisms (SNPs) were obtained using the genotyping by sequencing technique while RNA sequencing was used to measure gene expression in three regions of the brain.
The study demonstrated the value of this approach in uncovering genes associated with a wide array of complex trains. Specifically, it also revealed that CFW mice seem to have abnormally high bone mineral density (BMD) and that this 'abnormal BMD' phenotype is strongly associated with a chromosome 5 locus. This locus contains a large number of genes, including Abcf2 and Slc4a2. The human ortholog ABCF2 has been associated with BMD in the largest GWAS of BMD completed thus far while Slc4a2 is known to play a role in osteoclasts in mice and cattle.
Editor’s comment: Another GWAS of multiple complex traits in outbred mice recently found the musculoskeletal-relevant genes including Bmp2, which codes for bone morphogenetic protein, were associated with wound healing. Prkca, a gene encoding protein kinase Cα, which promotes osteoblast proliferation, was associated with bone mineral content.
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