IBMS BoneKEy | Perspective

The future of mouse genetics in osteoporosis research

Cheryl L Ackert-Bicknell
Clifford J Rosen

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DOI:10.1138/20090380

Abstract

Focused studies examining the genetics of osteoporosis in the mouse began approximately fifteen years ago, but as these studies have progressed it has become apparent that the genetics of osteoporosis is more complicated than originally predicted. Traditional F2 inter-cross mapping in the mouse, while valuable, is going to fall short of the goal of mapping all of the genes underlying this disease. In the past three years there has been considerable development of new techniques and resources for mouse genetics. Herein we describe four such mouse genetic resources and/or techniques that can be readily applied to the study of osteoporosis. First we describe a de novo mouse genetic map that has been developed to alleviate historical marker order problems and a tool that can be used to convert between the genetic map and the physical genome sequence map. We describe haplotype association mapping, a QTL mapping technique that can be used in concert with traditional mapping to identify the underlying genes. We also describe expression QTL mapping and how this technique can be used to augment gene discovery efforts. Lastly, we describe the Collaborative Cross, an ambitious set of recombinant inbred mouse strains currently in production. The application of these and other new tools, techniques and resources will accelerate gene discovery and further our understanding of the genetics of osteoporosis.

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