GENETIC STUDIES OF NONSYNDROMIC DEAFNESS

描述(改编自《调查者摘要》)：语前聋 在病因上是异质性的，有许多已知的遗传和环境 原因。在这个国家，它在出生时或儿童早期的发病率是 每1000人中约有0.8人。以前的研究表明，核突变 或者线粒体基因约占所有深部病变病例的一半。 耳聋。在这些病例中，大约80%-90%的遗传性耳聋是一种 孤立性异常，以隐性传递最常见 遗传模式。 据估计，至少有36-103个独立的基因座能够 产生耳聋的。22个非综合征基因的染色体定位 耳聋已经被证实，但相对频率 这些基因座的突变代表着现有知识中的一个重要缺口。 这项研究的目标是确定基因突变的频率 这些基因座并映射其他耳聋基因座。 在拟议的五年研究中，调查人员将(1) 确定大的多代家系和较小的血缘关系 通过弗吉尼亚州加劳德特大学的资源和 蒙古乌兰巴托聋人学校；(2)在这些地区进行联动测试 已知耳聋基因的家族并寻求识别这些基因的突变 与这些基因连锁的家系；(3)进行10 cM基因组筛查 关于8-13个大的多世代家系，总计约235个 个人和340个近亲家庭，其中大约一半将是 多种多样；(4)跟进这些家庭的初步建议 努力确认和精细定位负责的基因；以及(5)开始 主要通过位置候选策略来识别基因。 每年将进行大约50,000次基因分型。在……里面 此外，聋校所有在校学生的血迹 将对乌兰巴托的线粒体突变进行筛查 与链霉素敏感有关。

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.