Genetic hearing screening and diagnosis facilitated by using a combined low-cost

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DESCRIPTION (provided by applicant): Universal newborn hearing screening is a widely-adopted clinical practice and mandated by law in the United States. Current physiology-based hearing screening protocol generates high false positive rate and is unable to detect early-onset hearing loss and provide a diagnosis that defines underlying etiology. Studies have indicated that the primary diagnostic concern in congenital hearing loss is genetic mutations in deafness genes and infections with cytomegalovirus. Recent advances in massively-parallel sequencing technologies have made it possible to routinely analyze targeted sets of human genes totaling millions of base pairs. However, the new technology has not been validated with deafness genes. More importantly, the high cost associated with capturing targeted deafness genes makes it unlikely that these technological advances will be translated into a widely-adopted clinical tool. The R21 phase of the project will test and validate the core technology for a low-cost approach to efficiently capture exons of most common deafness genes and its suitability for coupling with various types of downstream sequencing applications by massively parallel sequencers for the detection of genetic mutations. In the R33 phase we will expand the capturing coverage of our custom genechips to include all confirmed deafness genes and deafness gene candidates. The overall goal of the project is to provide a cost-competitive and mature implementation protocol for a DNA-based approach for hearing screening that will significantly enhance the current universal newborn hearing screening program. PUBLIC HEALTH RELEVANCE: Recent advances in massively-parallel sequencing technologies have made it possible to routinely analyze targeted sets of human genes totaling millions of base pairs. However, the new technology has not been validated with deafness genes and the high cost associated with capturing targeted deafness genes makes it unlikely that these technological advances will be translated into a widely-adopted clinical tool. This project will test and validate the core technology for a low-cost approach to efficiently capture exons of all confirmed deafness genes and deafness gene candidates. The overall goal of the project is to provide a DNA-based hearing screening method that will significantly enhance the current universal newborn hearing screening program.