This is a pilot study grant application for a genetic study of Hodgkin's disease (HD). The grant includes two parts. Part I is to collect blood samples from 200 sib pairs affected with HD and their parents through national and international collaborations, and to use DNA microsatellites in candidate regions to identify genes contributing to HD, and to examine gene-environment interaction in etiology of HD. Approximately 20 DNA markers, including HLA and non-HLA regions which were documented to have an association with HD will be tested. Part II is a meta analysis for pre-existing familial HD data with HLA haplotype information pooled from the literature. The main focus in Part I is 1) to test the hypothesis of a major gene factor to estimate age specific penetrance using complex segregation analysis and 2) to test the hypothesis of linkage and quantify the proportion of HLA linked or non- linked families using lod score approach and non-parametric linkage analysis and 3) to estimate relative risk in sibs based on HLA haplotype information. preliminary study for the purpose of Part I has been carried out on 63 HD patients. We tested one DNA marker named DQCARIII in the HLA class 11 region. The results support a weak association between HD and the marker DNA (P value =0.06). This naturally provides a candidate gene for our study. For the purpose of Part II, 60 multiple families from the published literature have been identified. That data is being entered and verified at the current time. In summary, we believe that this is a feasible approach and can serve as a first step towards future breakthroughs in our understanding of HD by addressing the association between DNA markers and HD, and by thoroughly examining the genetic mode of inheritance of HD through sophisticated statistical tools.
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