CREATION OF A DNA REPOSITORY TO IDENTIFY DEAFNESS GENES

这项提议的目标是建立一个庞大的呼吸DNA样本，从2000聋人先证者的多重和单一的兄弟姐妹。然后将使用顺序筛选策略来识别导致耳聋的新基因。待筛选的候选基因将包括小鼠耳聋基因的人类同源基因，以及某些已知导致耳聋的基因家族的其他成员。研究对象将从加劳德特大学聋哑学生和该大学学生的年度全国调查中确定。该研究还将提供有关目前公认的综合征性和非综合征性耳聋基因突变分布的重要信息。利用相关结果变量的现有信息，如听力图和助听器和人工耳蜗的使用，这些数据将允许搜索临床相关的基因型-表型相关性。所得数据将用于寻找耳聋基因频率的种族差异，以及耳聋发病率的长期趋势。多重和单一兄弟姐妹中常见形式耳聋的频率将被用作指标特征来估计年度调查人群中耳聋的相对频率。最后，计算机建模将被用来探索聋人之间非随机交配的后果，并测试这种假设，即分类交配导致了由Connexin 26基因突变引起的一种常见形式的遗传性耳聋的高频率。

The goal of this proposal is to establish a large respiratory of DNA samples from 2,000 deaf probands in multiplex and simplex sibships. A sequential screening strategy will then be used to identify new genes for deafness. Candidate genes to be screened will include the human orthologs of murine genes for deafness and other members of gene families in which some are known to be the cause of deafness. The research subjects will be ascertained from an Annual National Survey of Deaf Students at Gallaudet University along with students from the University. The research will also yield important information on the distribution of mutations at currently recognized genes for syndromic and non- syndromic deafness. Using available information on relevant outcome variables such as audiograms and the use of hearing aids and cochlear implants, these data will permit a search for clinically relevant genotype-phenotype correlations. The resulting data will be used to search for ethnic differences in the frequency of genes for deafness as well as secular trends in the incidence of deafness. The frequency of common forms of deafness in multiplex and simplex sibships will be used as index traits to estimate the relative frequency of deafness in the Annual Survey population. Finally, computer modeling will be employed to explore the consequences of non-random mating among the deaf and to test the hypothesis that assortative mating has contributed to the high frequency of a common form of genetic deafness caused by mutations in the Connexin 26 gene.