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系统，收集2000名聋人先证者的DNA样本，这些先证者来自多个和单一的兄弟姐妹。然后将使用顺序筛查策略来识别新的耳聋基因。待筛选的候选基因将包括人类与小鼠耳聋基因的同源基因，以及基因家族的其他成员，其中一些已知是导致耳聋的原因。研究对象将从加劳德特大学的年度全国聋人学生调查中确定，还有该大学的学生。这项研究还将提供有关目前公认的症状性和非症状性耳聋基因突变分布的重要信息。利用有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上相关的基因-表型相关性。由此产生的数据将被用来搜索耳聋基因频率的种族差异以及耳聋发病率的长期趋势。多重和单重兄弟姐妹中常见类型耳聋的频率将被用作指数性状，以估计年度调查人群中耳聋的相对频率。最后，将利用计算机建模来探索聋人之间非随机交配的后果，并测试分类交配导致连接蛋白26基因突变导致的一种常见遗传性耳聋的高频率这一假设。

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.