中国西北地区非综合征型耳聋常见聋病基因突变图谱的绘制及分析

发布时间：2018-05-06 11:49

本文选题：中国 + 西北地区　；参考：《兰州大学》2010年硕士论文

【摘要】： 听觉在人类进行社会活动和日常生活中具有不可替代的重要作用。听觉功能障碍表现为不同程度的听力损失,是导致言语交流障碍的常见疾病,是人类最大的苦难之一。研究发现：遗传和／或环境因素均可致聋,而仅由遗传引起的至少占50%,与耳聋相关的基因超过了140个。然而,大部分遗传性耳聋仅仅与少数耳聋相关基因的突变有关。中国西北地区的五个省、自治区面积大,人口、民族分布很不一致,经济文化相对落后。为了解该地区非综合征型耳聋群体的病因学特点,探讨遗传因素在耳聋发病中的规律,本课题在2004-2009年原有甘肃、青海和新疆样本的基础上,进一步对陕西、宁夏的耳聋患者进行研究,对整个中国西北耳聋人群的常见两个耳聋基因突变图谱进行了初步的绘制,快速、高效分析了解耳聋的概况,以利于为该地区耳聋基因诊断的和遗传咨询奠定基础,为政府制定有效的而针对性的防聋治聋的政策措施提供科学依据。第一部分中国西北地区非综合征型耳聋患者线粒体DNA 12SrRNAm.1555AG突变图谱的绘制和分析及新突变的探索分析本部分研究通过对来自中国西北地区的陕西、甘肃、青海、宁夏、新疆共2398例非综合征型耳聋患者进行线粒体DNA 12SrRNAm.1555AG突变图谱的绘制,结果发现126例患者携带m.1555AG均质性突变；1例异质性改变,均质性突变携带频率为5.25%(126/2398)。在126例突变携带者中发现52例有明确的氨基糖苷类抗生素应用史,该结果提示氨基糖苷类抗生素的使用是该地区聋哑人群中m.1555AG突变检出率较高的重要原因。统计学分析结果显示m.1555AG突变携带率在中国西北不同地区、民族之间均有差别。同时发现的包括m.1556CT在内的26个核苷酸改变位点,与耳聋的相关性尚需更深入的研究。第二部分中国西北地区非综合征型耳聋患者GJB2基因突变图谱的绘制与分析及特殊突变的相关分析本部分研究在第一部分的基础上,进一步对2398例非综合征型耳聋患者进行了GJB2基因编码区突变图谱的绘制。明确了10.2%(245/2398)的患者为GJB2基因突变所致。经统计学分析显示：在不同地区、不同民族GJB2基因突变携带率均有差别,尤其是热点突变在主要的四个民族汉族、回族、维吾尔族和藏族有所不同,c.235delC是每个民族的热点突变,但是四个民族的携带率并不一致；而高加索人群的热点突变c.35delG在三个主要民族(汉族、回族和维吾尔族)的携带率也有差别。本研究同时还发现了GJB2基因突变所致的三个显性遗传家系,最后对一种突变命名进行了校正,进一步丰富了GJB2基因突变相关内容。
[Abstract]:Hearing plays an irreplaceable role in human social activities and daily life. Hearing impairment is a common disease that leads to speech communication disorder, and it is one of the greatest human suffering. The study found that genetic and / or environmental factors can cause deafness, while genetic factors alone account for at least 50%, with more than 140 genes associated with deafness. However, most hereditary deafness is only associated with mutations in a few deaf-related genes. The five provinces in Northwest China have a large area, different population and ethnic distribution, and relatively backward economy and culture. In order to understand the etiological characteristics of non-syndromic deafness population in this area and to explore the regularity of genetic factors in the onset of deafness, this study was based on the original samples of Gansu, Qinghai and Xinjiang from 2004 to 2009. Based on the study of deafness patients in Ningxia, a preliminary mapping of the mutations of two common deafness genes in the whole population of deafness in northwest China was carried out. The general situation of deafness was analyzed quickly and efficiently. In order to lay the foundation for genetic diagnosis and genetic counseling of deafness in this area and provide scientific basis for the government to formulate effective and targeted policies and measures to prevent deafness and cure deafness. Part one: mapping and analysis of mitochondrial DNA 12SrRNAm.1555AG mutations in patients with non-syndromic deafness in northwest china In this part of the study, 2398 patients with non-syndromic deafness from Shaanxi, Gansu, Qinghai, Ningxia and Xinjiang were studied by mapping mitochondrial DNA 12SrRNAm.1555AG mutations. The results showed that 1 patient with m.1555AG homogeneity mutation had heterogeneity change, and the frequency of homogenous mutation was 5.25%, 126.2398%. 52 of 126 mutants were found to have a definite history of using aminoglycoside antibiotics. The results suggest that the use of aminoglycoside antibiotics is an important reason for the high detection rate of m.1555AG mutation in the deaf and mute population in this area. The results of statistical analysis showed that there were differences among ethnic groups in different regions of northwest China. At the same time, the association of 26 nucleotide change sites, including m.1556CT, with deafness needs further study. Part II: mapping and analysis of GJB2 gene mutations in patients with non-syndromic deafness in Northwest China and correlation analysis of special mutations On the basis of the first part, 2398 patients with non-syndromic deafness were further mapped for the mutation of GJB2 gene coding region. It was determined that 10. 2% of the patients were caused by mutations in the GJB2 gene. Statistical analysis showed that there were differences in GJB2 gene mutation rates among different ethnic groups in different regions, especially in the four major ethnic groups, Han, Hui, Uygur and Tibetan, which were different from each other in that C. 235delC was the hot spot mutation of each ethnic group. However, the carrier rates of the four ethnic groups are not the same, and there are differences among the three major ethnic groups (Han, Hui and Uygur) for the hot spot mutation c.35delG of Caucasian population. At the same time, three dominant genetic families caused by GJB2 gene mutation were found. Finally, a mutation naming was corrected, which further enriched the related contents of GJB2 gene mutation.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R764.43

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