Finding Genes for Cancer Susceptibility and Growth Regul

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Dr. Ostrander?s research interests are in the area of genetic mapping and genomics. We have two main areas of interest. First, we are mapping and cloning genes that, when mutated, increase the risk of breast and prostate cancer in humans. Both family based and population based studies are underway. Second, we are interested in the development of the canine system for both understanding natural genetic variation as well as identifying disease genes. Trainees interested in human cancer have the opportunity to work on both breast and prostate cancer. Recently, we completed a genome wide scan of 255 prostate cancer families. Analyses of our data thus far has shown that prostate cancer is extremely heterogeneous, and that multiple loci are likely to be important. Stratification of our now complete genotyping dataset by clinical features of disease and family history are suggest multiple regions of interest where prostate cancer genes are likely to lie. With regard to breast cancer we have focused on analysis of BRCA1 and BRCA2 mutations in women with breast cancer in several case-control settings. Our work has led to studies of gene-gene and gene-environment interactions that provide new hypotheses for future studies. Our most recent work has focused on a large data set of nearly 3000 women, of whom about 1/3 are African American, providing one of the largest data sets of information about inherited susceptibility and breast cancer in this poorly studied group of patients. In addition, we are taking an evolutionary approach to understanding cancer susceptibly genes and have cloned portions of BRCA1 and BRCA2 from a number of marsupials. This has allowed us to hypothesize a set of missense changes that are likely disease associated. With regard to the canine system we and our collaborators have developed a dense comparative map between humans, dogs and mice and participated in the sequencing of the dog genome. We are now using those resources to map genes important in a variety of diseases, most notably cancer. Additional studies focus on finding genes important in growth regulation and development by working closely with dog owners, breeders and kennel clubs and collecting both DNA samples and recording growth measurements. Finally, we are interested in the organization of the canine family tree and the utility of linkage disequilibrium for mapping canine genes of interest. Towards that end, studies begun last year continue as we seek to understand the relationship of dog breeds one to another and ultimately to wolf ancestors.