中文摘要：

间隙连接蛋白β2（GJB2）基因突变与遗传性非综合征性耳聋密切相关,其广泛的突变类型及特异性的热点突变被认为是一种独特的致聋基因。本研究应用生物信息学方法对17个物种的GJB2蛋白进行了系统发育、保守性、跨膜区结构、三维结构和错义突变的分析,并结合已有报道的实验结果进行关联性分析。分析预测获得了166个固定的氨基酸位点、2个非保守区以及2个空间结构保守位点;关联性分析证实发生在保守位点的突变致病性高,非保守区突变的概率致病性小,跨膜区且改变氨基酸性质的突变,可能影响蛋白的空间结构而改变膜通道的通透性。本文为进一步研究GJB2基因突变与聋病的关联性及分子发病机制提供了理论依据,同时,这种研究思路对其它疾病的相关研究具有一定的借鉴价值。

英文摘要：

Gap junction protein β2 （GJB2） gene mutations are close associated with the hereditary non-syndromic hearing loss.Because of their wide mutation types and specific high frequency mutations,it was considered to be an unique deafness gene.In this research,GJB2 proteins were systematically studied with the means of bioinformatics including molecular phylogeny,conservation,transmembrane region,three-dimensional structure and missense mutation analysis,and also correlation analysis was carried out by combining some previous reported experimental results.166 amino acid fixed sites,two non-conserved regions and 2 sites of conserved spatial structure were predicted.Association analysis confirmed that high pathogenicity was the occurrence of mutations in the conserved sites,low probability of pathogenicity happened in non-conservative mutations as well.The mutations in transmembrane regions with the property of amino acid changing may affect the spatial structure of proteins leading to change the permeability of membrane channels.This study would provide a theoretical basis for further study of the deafness associating with GJB2 gene mutations and molecular mechanics of pathogenesis,and also the research ideas have a certain reference value for other diseases.