In a recent study, the Farber lab in the CPHG and a group of researchers at UCLA have used genome-wide association (GWA) and systems genetics in the mouse to identify and functionally characterize novel genes influencing bone mineral density (BMD), a complex phenotype that is strongly associated with bone strength. The researchers used GWA to identify four regions of the mouse genome that were associated with BMD. The additional sex combs like-2 (Asxl2) gene was found to underlie one of these associations. The authors then used a novel network-based approach to determine that Asxl2 influences bone mass by altering the activity of bone resorbing osteoclasts. This study demonstrates the power of systems genetics for both gene discovery and elucidating gene function. The full text of “Mouse Genome-Wide Association and Systems Genetics Identify Asxl2 as a Regulator of Bone Mineral Density and Osteoclastogenesis” can be found in the April issue of PLoS Genetics.
Charles Farber is an Assistant Professor of Medicine, Cardiovascular Medicine. His research interests include genetics of complex disease with an emphasis on the systems genetic analysis of complex skeletal phenotypes in the mouse.