The scientific goal of this NRSA fellowship proposal is to learn modern statistical genetic methods to elucidate the role of genetic factors influencing the expression of a common form of brachydactyly - BDA3. Preliminary investigation of hand-wrist radiographs indicates a high prevalence of this brachydactyly in the Jirel population, an endogamous population in eastern Nepal. There are two phenotypes of interest - BDA3 and BDA3 with cone-shaped epiphyses. When these forms of brachydactyly appear alone, they are asymptomatic of other major developmental disorders. For this reason they have received little attention over the decades, and certainly since the advent of modern statistical genetic tools. This presents an excellent training opportunity for the applicant. The training plan includes segregation analysis, quantitative genetic analysis, and linkage analysis. These training and scientific goals will be accomplished by analyzing the presence or absence of BDA3 or BDA3 with cone-shaped epiphyses. These data are available from existing hand-wrist radiographs from over 1,300 child participants of the NIH funded Jiri Growth Study, as well as from hand-wrist radiographs that will be collected from approximately 1,400 adult relatives participating in the Jiri Helminth Project. Additionally, extensive pedigree data is available, and over 90% of the study participants will have been genotyped by the time linkage analyses will be conducted. These data and other resources at Wright State University School of Medicine's Lifespan Health Research Center and the Southwest Center for Biomedical Research offer a thoroughly unique opportunity to explore the genetic architecture of this hand anomaly, and for the applicant to expand her skill set within the field of skeletal biology. ? ? ?
