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

项目概要/摘要 普遍新生儿听力筛查是一种广泛采用的临床实践， 美国的目前基于生理学的听力筛查方案产生高假阳性率， 检测早发性听力损失并提供定义潜在病因的诊断。研究表明 先天性听力损失的主要诊断问题是耳聋基因的基因突变和感染 巨细胞病毒感染并行测序技术的最新进展使得有可能 常规分析目标人类基因组，总计数百万个碱基对。然而，新技术并没有 已经被耳聋基因证实了。更重要的是，与捕获目标耳聋相关的高成本 基因的复杂性使得这些技术进步不太可能转化为广泛采用的临床工具。 该项目的R21阶段将测试和验证核心技术，以低成本的方式有效地 捕获大多数常见耳聋基因的外显子及其与各种类型的下游基因偶联的适用性 大规模并行测序仪用于检测基因突变的测序应用。在R33阶段 我们将扩大我们定制基因芯片的捕获范围，以包括所有已确认的耳聋基因， 耳聋基因候选者。该项目的总体目标是提供一个具有成本竞争力和成熟的 一个基于DNA的听力筛查方法的实施协议，将大大提高目前的 新生儿听力筛查计划

Project summary/abstract 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.