利用新一代测序技术进行线粒体突变相关耳聋表型的核基因调控机制研究

Deafness prevention is the century dream of countless medical scientists, patients and their families. With the rapid development of genomic medicine and technology advances in molecular biology, the desire of revealing the individual genetic background and individualized prevention of deafness will be come ture in the near future. In this project, we will sequence the mitochondrial genome and all nuclear deafness gene using exon capture technology, and make our greatest efforts to reveal the possible second mutation and nuclear modifier genes affect deafness phenotype caused by mitochondrial mutations. This study is on the basis of the the early Youth Science Fund. The subjects come from different audiology phenotypic subsets of the established database. The deafness phenotype influencing factors and regulatory mechanisms will be revealed collaborating with Youth Science Fund. The results of this project will be used to guide the clinical diagnosis and intervention of drug-induced deafness. It will provide theoretical foundation and technical support for individualized prevention of deafness and reduction of deafness birth defects.

耳聋预防是无数医学科学工作者和成千上万患者及其家庭的世纪梦想，随着基因组医学的迅猛发展和分子生物学技术的不断进步，全面揭示个体遗传背景、实现个体化预防耳聋发生的梦想即将成真。本课题在前期青年科学基金项目研究基础上，针对已经建立的线粒体突变个体数据库中不同听力学表型亚群，利用外显子捕捉技术，进行线粒体全基因组和核基因耳聋相关基因测序分析，从而揭示耳聋群体可能的第二突变，以及影响线粒体突变致聋表型的核修饰基因；协同青年科学基金项目的目标，共同阐释线粒体突变致聋的表型影响因素和调控机制。研究结果将用于指导药物性耳聋的临床诊断和干预，为实现耳聋个体化预防和减少耳聋出生缺陷提供理论基础和技术支持。

本项目为面上项目中的青年-面上连续资助项目，在前期青年科学基金项目研究成果基础上，信息化建立和完善了线粒体突变个体数据库，将所有样本进行了不同听力学表型亚群分型；利用外显子捕捉、生物编码和大规模平行测序技术，采用线粒体和核基因耳聋相关基因测序分析方法，对不同表型特征的线粒体12S rRNA A1555G突变个体进行了耳聋相关基因测序研究，绘制了以上携带线粒体突变个体的线粒体及核基因耳聋相关基因谱和突变谱，初步揭示了线粒体突变个体第二突变和表型差异的影响因素。本研究结果不仅丰富和完善了耳聋遗传异质性的发生机制，同时将用于指导线粒体突变相关耳聋的临床诊断和干预，为实现耳聋个体化预防和减少耳聋出生缺陷做出重要贡献。本项目共发表论著10篇（SCI文章5篇），参会论著1篇，培养博士研究生2名、技术人员2名。