GENETIC STUDIES OF NONSYNDROMIC DEAFNESS

描述（改编自研究者摘要）：语前聋 在病因学上是异质的， 可使. 其发病率在出生时或在幼儿期在这个国家是 大约千分之零点八。 先前的研究表明， 或线粒体基因占了所有深度感染病例的一半 耳聋 在大约80-90%的这些病例中，遗传性耳聋是作为一种 孤立性异常，隐性传播是最常见的 继承的模式。 据估计，至少有36-103个独立的基因座能够 产生耳聋。 22个非综合征型乳腺癌基因的染色体定位 耳聋已经建立，但相对频率 这些基因座上的突变代表了现有知识中的一个重要空白。 这项研究的目的是确定突变的频率， 这些基因座，并绘制额外的耳聋基因座。 在拟议研究的五年内，研究人员将（1） 确定大的多代系谱和较小的血缘关系 通过弗吉尼亚州Gallaudet大学的资源和 蒙古乌兰巴托聋人学校;（2）这些学校的联系测试 已知的耳聋基因，并寻求确定这些基因中的突变， 显示与这些基因连锁的家族;（3）进行10 cM基因组筛选 在8-13个大型多代谱系上，总共约235个 个人和340个近亲家庭，其中约一半将是 多重性;（4）跟踪这些家庭中连锁的初步建议， 努力确认和精细定位相关基因;（5）开始 主要通过位置候选策略来识别基因。 每年将进行约50，000次基因分型。 在 此外，所有聋哑学校的学生身上都有血迹 在乌兰巴托将筛选线粒体突变， 与对链霉素敏感有关。

DESCRIPTION (Adapted from the Investigator's Abstract): Prelingual deafness is etiologically heterogeneous with many known genetic and environmental causes. Its incidence at birth or during early childhood in this country is about 0.8 per 1,000. Previous studies have shown that mutations in nuclear or mitochondrial genes account for about half of all cases of profound deafness. In about 80-90% of these cases, genetic deafness occurs as an isolated abnormality, with recessive transmission being the most common pattern of inheritance. It is estimated that genes at least 36-103 independent loci are capable of producing deafness. The chromosomal locations of 22 genes for non-syndromic deafness have already been established, but the relative frequency of mutations at these loci represents an important gap in existing knowledge. The goal of this research is to determine the frequencies of mutations at these loci and to map additional deafness loci. Over the five years of the proposed study, the investigators will (1) ascertain large multigenerational pedigrees and smaller consanguineous pedigrees through the resources of Gallaudet University in Virginia and the School for the Deaf in Ulaanbaatar, Mongolia; (2) test for linkage in these families to known deafness genes and seek to identify mutations in those families showing linkage to these genes; (3) carry out a 10 cM genome screen on 8-13 large multigenerational pedigrees with a total of about 235 individuals and on 340 consanguineous families, about half of which will be multiplex; (4) follow up initial suggestions of linkage in these families in an effort to confirm and fine map the responsible genes; and (5) begin to identify the genes primarily by means of the positional candidate strategy. A total of about 50,000 genotypings will be performed each year. In addition, blood spots from all available students at the School for the Deaf in Ulaanbaatar will be screened for the mitochondrial mutation that is associated with sensitivity to streptomycin.