视网膜色素变性大家系致病新基因的克隆鉴定及功能研究

视网膜色素变性(RP)是一种异质性很高的遗传性疾病，其发病率约为1/3800，且致病基因多、遗传方式多样。目前已克隆超过67个致病基因，还有很多RP致病病因并不清楚。随着二代测序技术的发展，遗传病疾病基因克隆的效率大大提高。抢占战略高地，掌握遗传病资源，是疾病基因克隆鉴定的重要基础。本课题以收集的川南地区RP家系60多个为研究对象，使用目标基因测序，基因Panel筛查，发现一个RP大家系的致病基因未知，然后使用全外显子测序及生物信息分析，发现RP新的致病基因。因此，本课题的研究旨在：1.新的RP致病基因在其它家系的突变分析与确证，克隆和鉴定新的RP致病基因，揭示RP的新病因；2.在生物信息学、细胞与分子生物学、免疫组化以及蛋白结构与功能的关系等多层次初步探讨该致病基因生物学功能，及与RP的关系。本项目的顺利实施，揭示RP新病因，为基因诊断提供理论基础，具有很重要的科学意义。

Retinitis pigmentosa (RP) is a high genetically heterogeneous disease. The incidence rate is about 1/3800, a number of disease-causing genes with genetic diversity are related to RP. Right now there have cloned more than 67 of RP-causing genes, but there are many patients with RP pathogenic cause are unclear. With the development and application of next-generation sequencing technology, disease gene cloning of genetic disease success rate is greatly increased. Seize the strategic high ground, master genetic disease resources, it is an important underlying disease clone identification. We have collected more than 60 pedigrees of RP disease from Southern regions of Sichuan so far. By using the target gene sequencing, gene panel screening, we have found a big pedigree, but the disease gene is unknown. Now using the whole exon sequencing, and bioinformatic analysis, we want to find a novel disease gene for RP. Therefore, our research project is as follows: first，new RP mutation analysis of the causative genes in pedigrees; cloning and identification of new disease genes, reveal new causes of the RP; second, at the bioinformatics, cellular and molecular biology, immunohistochemistry, and the protein structure and function relationship to explore the causative gene, and its relationship with RP. With successful implementation of this project, we can identify novel gene responsible for RP, providing the theoretical basis for the gene diagnosis, which has very important scientific significances and application values.