title: Identification and in silico analysis of functional SNPs of the BRCA1 gene.
abstract: Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. Also, the genetics of human phenotype variation could be understood by knowing the functions of these SNPs. It is still a major challenge to identify the functional SNPs in a disease-related gene. In this work, we have analyzed the genetic variation that can alter the expression and the function of the BRCA1 gene using computational methods. Of the total 477 SNPs, 65 were found to be nonsynonymous (ns) SNPs. Among the 14 SNPs in the untranslated region, 4 were found in the 5' and 10 were found in the 3' untranslated region (UTR). It was found that 16.9% of the nsSNPs were damaging, by both the SIFT and the PolyPhen servers. The UTR Resource tool suggested that 2 of 4 SNPs in the 5' UTR and 3 of 10 SNPs in the 3' UTR might change the protein expression levels. We identified major mutations from proline to serine at positions 1776 and 1812 of the native protein of the BRCA1 gene. From a comparison of the stabilizing residues of the native and mutant proteins, we propose that an nsSNP (rs1800751) could be an important candidate for the breast cancer caused by the BRCA1 gene.
authors.affiliation: School of Biotechnology, Chemical, and Biomedical Engineering, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu, India.
authors.forename: R
authors.initials: R
authors.lastname: Rajasekaran
authors.forename: C
authors.initials: C
authors.lastname: Sudandiradoss
authors.forename: C George Priya
authors.initials: CG
authors.lastname: Doss
authors.forename: Rao
authors.initials: R
authors.lastname: Sethumadhavan
mesh_terms: D019313:BRCA1 Protein / Q000737:chemistry; D001943:Breast Neoplasms / Q000235:genetics; D019295:Computational Biology; D004252:DNA Mutational Analysis / Q000379:methods; D030541:Databases, Genetic; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D006801:Humans; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D050505:Mutant Proteins