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确定心肌病相关基因突变的路线图:贝叶斯方法。

Roadmap to determine the point mutations involved in cardiomyopathy disorder: a Bayesian approach.

机构信息

Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu, India.

出版信息

Gene. 2013 Apr 25;519(1):34-40. doi: 10.1016/j.gene.2013.01.056. Epub 2013 Feb 9.

Abstract

Determining the deleterious non-synonymous single nucleotide polymorphisms (nsSNPs), that might be involved in inducing disease-associated phenomena, is now among the most important field of computational genomic research. The rapid evolution in sequencing technologies has now outranged the limit of available sequence databases and has out-fledged the amount of SNP data that are yet to be characterized. In this article we have performed a comprehensive analysis of deleterious nsSNPs in MyH7 gene associated with cardiomyopathy cases using a set of computational platforms. We implemented a set of computational SNP analysis platforms along with the Bayesian calculations in order to filter the most likely mutation that might be associated with cardiomyopathy associated disorders. The Bayesian calculation depicted 27 fold rises in the likelihood score for causing cardiomyopathy disorder when MyH7 gene mutations were compiled. Furthermore, we reported E466Q mutation in MyH7 motor domain that showed increase in the amyloid propensity of protein, as well as a significant level of pathogenicity was also observed. The prediction roadmap followed in this article has showed a notable range of accuracy and can be used for determining cardiomyopathy associated nsSNPs for other candidate genes.

摘要

确定可能导致疾病相关现象的有害非同义单核苷酸多态性(nsSNP),现在是计算基因组学研究中最重要的领域之一。测序技术的快速发展已经超出了现有序列数据库的限制,并超出了尚未被描述的 SNP 数据量。在本文中,我们使用一组计算平台对与心肌病病例相关的 MyH7 基因中的有害 nsSNP 进行了全面分析。我们实现了一组计算 SNP 分析平台以及贝叶斯计算,以筛选可能与心肌病相关疾病相关的最可能的突变。贝叶斯计算描绘了当 MyH7 基因突变时,导致心肌病紊乱的可能性评分增加了 27 倍。此外,我们报告了 MyH7 运动域中的 E466Q 突变,该突变显示出蛋白淀粉样倾向的增加,并且还观察到了显著的致病性水平。本文中遵循的预测路线图显示了相当高的准确性范围,可用于确定其他候选基因与心肌病相关的 nsSNP。

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