乳腺癌易感蛋白1序列结构特征及致病性突变的分析

Analysis on the sequence and molecular structure of breast cancer susceptibility protein 1 and its mutagenesis to pathogenicity

目的:利用生物信息学方法分析乳腺癌易感基因1(BRCA1)序列结构特征,并预测BRCA1功能编码区突变与致病性遗传效应的关系。方法:采用Maximum Likelihood、ClustalW、SMART和Selecton等在线生物信息学分析工具,对BRCA1进行分子系统发育、保守性、选择压力、结构域、三维结构和错义结构的分析。结果:分析获得195个固定残基位点(10.5%)和393个保守位点(21.1%),其分布是非随机性的;发现人BRCA1序列中的保守结构域BRCT的三维结构与其他物种存在着较大的差异,表明BRCT结构域在不同物种中具有不同的生物学功能;关联性分析证实发生在保守位点的突变致病性高。结论:基于生物信息学的BRCA1序列结构分析,能充分利用相关数据的资源,加深对BRCA1基因变异与肿瘤发生的相关性的认识。

Objective：To analyze the structure characteristics of the breast cancer susceptibility protein 1 （BRCA1） gene sequence by bioinformatics methods and predict the relationship between mutations of functional coding regions in BRCA1 and the pathogenic genetic effects. Methods：The molecular phylogeny, conservation, selection pressure, domains,three-dimensional structure and mis- sense of BRCA1 were analyzed by online Bioinformatics analysis tools such as Maximum Likelihood,ClustalW,SMART,SELECTON and so on. Results：Total 195 fixed-residue sites（10.5%）and 393 conservative sites（21.1%）,of which distribution is non-randomness, were obtained. A big difference in the BRCT domain was founded between human and other species,which indicated the role of BRCT domain in BRCA1 gene of various species is difference. The high pathogenic mutation rate in conservative sites was confirmed by correlation analysis. Conclusion：Taking full advantage of relevant resources,the BRCA1 sequence structure analysis based on bioinformatics methods can deepen our understanding of the correlation of BRCA1 gene mutation and tumor.