一个Goldenhar综合症自然村落的遗传学研究

Goldenhar Syndrome (GS) is a multi-systemic deformity involving the eye, the ear, the spine, the craniofacial and the other organ-development. For more than half a century, scientists worldwide have carried out huge scale of work for investigating the mechanism of GS. However, to now, the inheritance and the disease-causing gene of GS remain undefined. Two important factors that acting each other were obstacles for identifying the disease-causing gene of GS. The one factor was the unavailability of a large GS family at the investigation of GS. The second factor was, at the previous time, the unavailability of a series of advanced genetic techniques fitting for the discovery of GS disease-causing gene. In this study, we intended to identify the inheritance and the disease-causing gene of GS. For this end, a special GS village will be investigated with the main focus to the GS inheritance, the special GS phenotypes. A series of genetic experiments including comparative genomic hybridization, whole genome low-coverage sequencing, STR/SNP genomic linkage analysis and whole exome sequencing will be performed on the special GS village and other collected GS patients.

Goldenhar综合症（GS）是一种涉及眼、耳、脊柱等多器官系统先天发育畸形，其发病率为1/5000-6000。半个多世纪以来，人类对GS遗传学发病机制的研究付出了巨大努力，开展了大量研究工作，提出了较多的设想。至今，GS的遗传模式和分子遗传学基础仍不明确。相互依赖、相互制约的在2个方面的因素，即缺乏研究GS致病基因的的大家系及与之遗传特点相匹配的联合研究方法，是不能有效定义GS致病基因的主要矛盾。本研究拟对我国某地区一个GS自然村落进行遗传学调查，掌握该村落GS遗传数据和临床表型特点后，对以该村落为核心的GS家系和散发病例行一整套的遗传联合技术研究，包括常规细胞遗传分析，基因拷贝数变异检测，全基因组低深度测序检测隐形染色体变异，基因组连锁分析，全基因组外显子捕获测序和相关基因功能研究，以达到揭示GS致病基因及其发病机制的目的，为人类认知自身发育提供新理论，为GS的临床防治提供直接依据。

Goldenhar综合症（GS）是一种涉及眼、耳、脊柱多器官系统先天发育畸形，其发病率为1/5000-6000。至今，GS的遗传模式和分子遗传学基础仍不明确。.项目组对我国桂东沙田地区的一个GS自然村落开展了遗传学调查，标本采集和疾病临床表型分析。随后对获取的标本开展了基于二代测序和全基因组连锁分析的多项实验，发现了1个新的GS致病基因区间，具体为13Mb的区间。项目组在该区间没有发现基因编码区致病性变异。相关后续非编码区致病性变异的研究正在开展。.与此同时，项目组围绕GS的重要表型还开展了多项研究工作，最新发现了BMPR1B基因的断裂重排导致先天性小下颌综合症；发现了中国人首例3号染色体三体的病例；发现GS表型与先天性尺桡骨融合相关；发现GS表型与21三体综合征密切相关。项目组在经费的支持下还取得了其它研究成绩。自本报告提交时间，本项目共发表了SCI论文7篇。相关研究的结果为人类认识自身疾病提供了新理论，为相关疾病的临床防治提供了直接依据。