Research in the Molecular Pathogenesis is focused on defining changes in the genes that underlie inherited susceptibilities to common diseases such as cancer, heart disease and birth defects. Currently under investigation are genes involved in inherited breast and ovarian cancer. Studies are designed to better understand the function and genetics of the BRCA1 and BRCA2 genes. Patients with familial breast and ovarian cancer are being screened for mutations in these genes. The biological function of the BRCA1 protein is currently unknown. This question is being addressed at the whole animal and biochemical level. A line of mice with a deletion in BRCA1 have been created. The mice are being bred with other tumor susceptible mice. Tumors from these mice will be tested for somatic mutations using comparative genome hybridization and spectral karyotyping. We have purified a portion of this protein used it to screen for other proteins that specifically interact with the BRCA1 protein. We have demonstrated that BRCA1 interacts with other proteins involved in chromatin remodeling and DNA repair including histone deactylase. An increased understanding of these genes will lead to improved diagnostic procedures and possible preventative therapies.