The goal of the research proposed 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 limiting in that a large number of affected individuals need to be analyzed to gain significant data. By ascertaining deaf individuals that carry balanced translocations, it becomes possible to discover disrupted genes with the genetic material of a single person. In this proposal, I plan to study two cases where the individual is deaf and carries a balanced translocation. Using the vast number of resources available now due to the progress made by the Human Genome Project, the sequence disrupted by these translocations will be identified. This will be done by progressively narrowing the breakpoint with FISH experiments using BACs and PCR products known to hybridize in the region. Candidate genes will then be identified by comparing the disrupted sequence to those already deposited in GenBank, or by analyzing these sequences with predication programs and methods. Ultimately, a mouse mutant may be created to confirm the pathogenesis of the disrupted gene.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DC005712-02
Application #
6640533
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Sklare, Dan
Project Start
2002-07-01
Project End
2005-03-31
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$28,810
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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
Williamson, Robin E; Darrow, Keith N; Giersch, Anne B S et al. (2008) Expression studies of osteoglycin/mimecan (OGN) in the cochlea and auditory phenotype of Ogn-deficient mice. Hear Res 237:57-65
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
Williamson, Robin E; Darrow, Keith N; Michaud, Sebastien et al. (2007) Methylthioadenosine phosphorylase (MTAP) in hearing: gene disruption by chromosomal rearrangement in a hearing impaired individual and model organism analysis. Am J Med Genet A 143A:1630-9