DISSERTATION RESEARCH: Modularity of Pleiotropic Effects on Skeletal Morphology.

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Many biologically important traits, including disease and size and shape, are influenced by multiple genes. This project will locate and identify genes affecting skeletal size and shape. We predict that mouse skeletal traits affected by common developmental and functional processes will share common gene effects and that traits affected by different processes will be affected by distinct sets of genes. For example, the femur and tibia are separate bones but are produced by the common outgrowth of the posterior limb bud so we expect variation in these bones to be affected by many of the same genes. In this project we survey the mouse genome for locations affecting 68 skeletal traits distributed throughout the skeleton and examine common patterns of gene effects for a hierarchical, modular structure. Digital photographs will be taken of 2250 mouse skeletons and traits measured using software for analyzing digital images. Locations in the genome that affect these traits will be identified statistically. Initial gene mapping is followed by a finer-scale map of selected genomic locations to identify the specific genes involved.This project will advance the understanding of the genetics of modularity for aspects of skeletal size and shape and its consequences for population processes. It also creates a resource of 50,000 skeletal digital images archived on DVD that will be available to other researchers. Biomedical studies and treatments for bone and growth-related diseases may also develop from this work in the future. Thus, this project also investigates theoretical aspects of the genetics of complex traits, thus contributing to health-related research as well.