Apoptosis and Cell Death Research Laboratory, Centre for Biomedical Research, School of Biosciences and Technology, Vellore Institute of Technology University Vellore, India.
Front Genet. 2014 May 27;5:148. doi: 10.3389/fgene.2014.00148. eCollection 2014.
Gaucher's disease (GD) is an autosomal recessive disorder caused by the deficiency of glucocerebrosidase, a lysosomal enzyme that catalyses the hydrolysis of the glycolipid glucocerebroside to ceramide and glucose. Polymorphisms in GBA gene have been associated with the development of Gaucher disease. We hypothesize that prediction of SNPs using multiple state of the art software tools will help in increasing the confidence in identification of SNPs involved in GD. Enzyme replacement therapy is the only option for GD. Our goal is to use several state of art SNP algorithms to predict/address harmful SNPs using comparative studies. In this study seven different algorithms (SIFT, MutPred, nsSNP Analyzer, PANTHER, PMUT, PROVEAN, and SNPs&GO) were used to predict the harmful polymorphisms. Among the seven programs, SIFT found 47 nsSNPs as deleterious, MutPred found 46 nsSNPs as harmful. nsSNP Analyzer program found 43 out of 47 nsSNPs are disease causing SNPs whereas PANTHER found 32 out of 47 as highly deleterious, 22 out of 47 are classified as pathological mutations by PMUT, 44 out of 47 were predicted to be deleterious by PROVEAN server, all 47 shows the disease related mutations by SNPs&GO. Twenty two nsSNPs were commonly predicted by all the seven different algorithms. The common 22 targeted mutations are F251L, C342G, W312C, P415R, R463C, D127V, A309V, G46E, G202E, P391L, Y363C, Y205C, W378C, I402T, S366R, F397S, Y418C, P401L, G195E, W184R, R48W, and T43R.
戈谢病（GD）是一种常染色体隐性遗传病，由溶酶体酶葡萄糖脑苷脂酶的缺乏引起，该酶催化糖脂葡萄糖脑苷脂水解为神经酰胺和葡萄糖。GBA 基因的多态性与戈谢病的发生有关。我们假设使用多种最先进的软件工具预测 SNPs 将有助于提高鉴定与 GD 相关 SNPs 的置信度。酶替代疗法是 GD 的唯一选择。我们的目标是使用几种最先进的 SNP 算法通过比较研究来预测/解决有害 SNPs。在这项研究中，使用了七种不同的算法（SIFT、MutPred、nsSNP Analyzer、PANTHER、PMUT、PROVEAN 和 SNPs&GO）来预测有害多态性。在这七种程序中，SIFT 发现 47 个 nsSNPs 是有害的，MutPred 发现 46 个 nsSNPs 是有害的。nsSNP Analyzer 程序发现 43 个 nsSNPs 中的 47 个是导致疾病的 SNPs，而 PANTHER 发现 32 个 nsSNPs 中的 47 个是高度有害的，PMUT 将 22 个 nsSNPs 中的 47 个分类为病理性突变，PROVEAN 服务器预测 44 个 nsSNPs 中的 47 个是有害的，SNPs&GO 显示所有 47 个是与疾病相关的突变。所有七种不同算法都共同预测了 22 个 nsSNPs。共同的 22 个靶向突变是 F251L、C342G、W312C、P415R、R463C、D127V、A309V、G46E、G202E、P391L、Y363C、Y205C、W378C、I402T、S366R、F397S、Y418C、P401L、G195E、W184R、R48W 和 T43R。
