The primary goal of this proposed research project is to determine the disease-causing mutation of the gene responsible for the seventeenth loci for autosomal recessive non-syndromic hearing loss (DFNB17), and to characterize its expression and function in the inner ear. Hereditary hearing impairment (HHI) affects approximately 1 in 1000 children and constitutes one of the most common birth defects. Because of the long-term problems with language acquisition, development and education, a further understanding of the pathophysiology of hearing impairment is warranted. Based on preliminary linkage data localizing the gene responsible for DFNB17 to a 3cM region of chromosome 7q31, we hypothesize that the deafness-causing mutation is contained within this interval. We will use a positional cloning strategy to test this hypothesis, identify the mutation responsible for DFNB17 and determine its putative functional and expression c characteristics. This project proposes to: 1) Refine and narrow the DFNB17 interval on chromosome 7q31. 2) Identify candidate cochlear expressed genes in the DFNB17 interval. 3) Identify the DFNB17 gene by determining the disease causing mutation in a family mapping the original locus and in novel families mapping to this interval. 4) Determine the expression pattern and putative function of this novel cochlear expressed gene. Secondarily, this project will serve as an opportunity for the principal investigator to acquire the skills and knowledge base to become an independent clinician-scientist. The immediate goals of the candidate are to establish an active research laboratory and study the DFNB17 gene. The long-term career goal is to be an independent clinician-scientist, focused on the study of the molecular genetics of hereditary deafness. Specifically, to identify novel hearing loss related genes, advance the science of molecular diagnostic testing for patients and provide insight into pathways for potential treatments in hearing impaired patients. All of this knowledge can then be directly applied to an otologically based clinical practice at a large pediatric tertiary care referral center to provide the highest quality of care for hearing impaired patients and families. The overall development plan to reach these goals will include a combination of dedicated laboratory time, integrating with and receiving direct support from the Division of Human Genetics with an educational plan which will consist of close association with mentor scientists, dedicated reading course, didactic inter- and extra-divisional interactive sessions and classes and prescribed lectures.
| Pilipenko, Valentina V; Reece, Alisa; Choo, Daniel I et al. (2004) Genomic organization and expression analysis of the murine Fam3c gene. Gene 335:159-68 |
| Guo, Yingshi; Pilipenko, Valentina; Lim, Lynne H Y et al. (2004) Refining the DFNB17 interval in consanguineous Indian families. Mol Biol Rep 31:97-105 |
| Li, R; Greinwald Jr, J H; Yang, L et al. (2004) Molecular analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in paediatric subjects with non-syndromic hearing loss. J Med Genet 41:615-20 |
