The goal of the proposed research is to use a cytogenetic approach to discover new deafness genes. Many genes of the auditory system have been identified through linkage studies of families that carry deafness as a heritable trait. This process is limited by the large number of affected individuals that need to be analyzed to gain significant data. By ascertaining deaf individuals that carry balanced chromosomal rearrangements, it is possible to discover disrupted or dysregulated genes with the genetic material of a single person. In this application, I plan to study a deaf family carrying a balanced paracentric inv(7) and two other deaf individuals carrying de novo balanced translocations. Using the resources made available through the Human Genome Project, the genes disrupted by these rearrangements will be identified. The breakpoints of the rearrangements will be mapped through FISH analysis and candidate genes will then be identified by comparing the disrupted sequence to the completed human genome maps. Mouse models will be created to confirm the pathogenesis of the disrupted genes. Analysis of the mice and in situ hybridization studies of the candidate genes in the cochlea will be used to establish the role of these genes in auditory function.
| Currall, Benjamin B; Chen, Ming; Sallari, Richard C et al. (2018) Loss of LDAH associated with prostate cancer and hearing loss. Hum Mol Genet 27:4194-4203 |
| Brown, Kerry K; Reiss, Jacob A; Crow, Kate et al. (2010) Deletion of an enhancer near DLX5 and DLX6 in a family with hearing loss, craniofacial defects, and an inv(7)(q21.3q35). Hum Genet 127:19-31 |
| Brown, Kerry K; Alkuraya, Fowzan S; Matos, Michael et al. (2009) NR2F1 deletion in a patient with a de novo paracentric inversion, inv(5)(q15q33.2), and syndromic deafness. Am J Med Genet A 149A:931-8 |
| Higgins, Anne W; Alkuraya, Fowzan S; Bosco, Amy F et al. (2008) Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project. Am J Hum Genet 82:712-22 |
