CREATION OF A DNA REPOSITORY TO IDENTIFY DEAFNESS GENES

这项计划的目标是建立一个大型的呼吸道的DNA样本，从2,000聋人先证者在多重和单一的同胞。 随后，将采用顺序筛选策略来确定耳聋的新基因。 待筛选的候选基因将包括用于耳聋的鼠基因的人类直系同源物和其中一些已知是耳聋原因的基因家族的其他成员。 研究对象将从加劳德特大学沿着该大学学生的全国聋人学生年度调查中确定。 这项研究还将产生关于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。 使用相关结果变量的可用信息，如听力图和使用助听器和人工耳蜗植入，这些数据将允许搜索临床相关的基因型-表型相关性。 由此产生的数据将被用来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。 在多亲兄弟姊妹和单亲兄弟姊妹中，常见失聪的频率会用作指标性状，以估计在按年统计调查人口中失聪的相对频率。 最后，计算机建模将探讨聋人之间的非随机交配的后果，并检验假设，即重复交配有助于高频率的一种常见形式的遗传性耳聋所造成的连接蛋白26基因突变。

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.