基因组学与应用生物学
基因組學與應用生物學
기인조학여응용생물학
Genomics and Applied Biology
2012年
1期
26-34
,共9页
范燚%喻岸竹%郁芸%韩新焕%邢光前%曹新
範燚%喻岸竹%鬱蕓%韓新煥%邢光前%曹新
범일%유안죽%욱예%한신환%형광전%조신
GJB2基因%非综合征型耳聋%分子进化%遗传效应%关联分析
GJB2基因%非綜閤徵型耳聾%分子進化%遺傳效應%關聯分析
GJB2기인%비종합정형이롱%분자진화%유전효응%관련분석
GJB2 gene%Non-syndromic hearing loss%Molecular evolution%Hereditary effect%Correlation analysis
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。
間隙連接蛋白β2(GJB2)基因突變與遺傳性非綜閤徵性耳聾密切相關,其廣汎的突變類型及特異性的熱點突變被認為是一種獨特的緻聾基因。本研究應用生物信息學方法對17箇物種的GJB2蛋白進行瞭繫統髮育、保守性、跨膜區結構、三維結構和錯義突變的分析,併結閤已有報道的實驗結果進行關聯性分析。分析預測穫得瞭166箇固定的氨基痠位點、2箇非保守區以及2箇空間結構保守位點;關聯性分析證實髮生在保守位點的突變緻病性高,非保守區突變的概率緻病性小,跨膜區且改變氨基痠性質的突變,可能影響蛋白的空間結構而改變膜通道的通透性。本文為進一步研究GJB2基因突變與聾病的關聯性及分子髮病機製提供瞭理論依據,同時,這種研究思路對其它疾病的相關研究具有一定的藉鑒價值。
간극련접단백β2(GJB2)기인돌변여유전성비종합정성이롱밀절상관,기엄범적돌변류형급특이성적열점돌변피인위시일충독특적치롱기인。본연구응용생물신식학방법대17개물충적GJB2단백진행료계통발육、보수성、과막구결구、삼유결구화착의돌변적분석,병결합이유보도적실험결과진행관련성분석。분석예측획득료166개고정적안기산위점、2개비보수구이급2개공간결구보수위점;관련성분석증실발생재보수위점적돌변치병성고,비보수구돌변적개솔치병성소,과막구차개변안기산성질적돌변,가능영향단백적공간결구이개변막통도적통투성。본문위진일보연구GJB2기인돌변여롱병적관련성급분자발병궤제제공료이론의거,동시,저충연구사로대기타질병적상관연구구유일정적차감개치。
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.