title: Computational and structural investigation of deleterious functional SNPs in breast cancer BRCA2 gene.
abstract: In this work, we have analyzed the genetic variation that can alter the expression and the function in BRCA2 gene using computational methods. Out of the total 534 SNPs, 101 were found to be non synonymous (nsSNPs). Among the 7 SNPs in the untranslated region, 3 SNPs were found in 5' and 4 SNPs were found in 3' un-translated regions (UTR). Of the nsSNPs 20.7% were found to be damaging by both SIFT and PolyPhen server among the 101 nsSNPs investigated. UTR resource tool suggested that 2 SNPs in the 5' UTR region and 4 SNPs in the 3' UTR regions might change the protein expression levels. The mutation from asparagine to isoleucine at the position 3124 of the native protein of BRCA2 gene was most deleterious by both SIFT and PolyPhen servers. A structural analysis of this mutated protein and the native protein was made which had an RMSD value of 0.301 nm. Based on this work, we proposed that this most deleterious nsSNP with an SNPid rs28897759 is an important candidate for the cause of breast cancer by BRCA2 gene.
authors: School of Biotechnology, Chemical and Biomedical Engineering, Bioinformatics Division, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu, India.
authors: R
authors: R
authors: Rajasekaran
authors: George Priya
authors: GP
authors: Doss
authors: C
authors: C
authors: Sudandiradoss
authors: K
authors: K
authors: Ramanathan
authors: Purohit
authors: P
authors: Rituraj
authors: Rao
authors: R
authors: Sethumadhavan
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D019943:Amino Acid Substitution; D051017:Apoptosis Regulatory Proteins; D024682:BRCA2 Protein / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D019295:Computational Biology; D024522:Genes, BRCA2; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human