title: In silico identification of genetic variants in glucocerebrosidase (GBA) gene involved in Gaucher's disease using multiple software tools.
abstract: 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.
authors.affiliation: Apoptosis and Cell Death Research Laboratory, Centre for Biomedical Research, School of Biosciences and Technology, Vellore Institute of Technology University Vellore, India.
authors.forename: Madhumathi
authors.initials: M
authors.lastname: Manickam
authors.affiliation: Apoptosis and Cell Death Research Laboratory, Centre for Biomedical Research, School of Biosciences and Technology, Vellore Institute of Technology University Vellore, India.
authors.forename: Palaniyandi
authors.initials: P
authors.lastname: Ravanan
authors.affiliation: Apoptosis and Cell Death Research Laboratory, Centre for Biomedical Research, School of Biosciences and Technology, Vellore Institute of Technology University Vellore, India.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Singh
authors.affiliation: Apoptosis and Cell Death Research Laboratory, Centre for Biomedical Research, School of Biosciences and Technology, Vellore Institute of Technology University Vellore, India.
authors.forename: Priti
authors.initials: P
authors.lastname: Talwar
keywords: MutPred; PANTHER; PMUT; PROVEAN; SIFT; SNPs&GO; glucocerebrosidase