ral ssBioMed CentJournal of Biomedical Science Open AcceResearch Investigation on the role of nsSNPs in HNPCC genes – a bioinformatics approach

Background: A central focus of cancer genetics is the study of mutations that are causally implicated in tumorigenesis. The identification of such causal mutations not only provides insight into cancer biology but also presents anticancer therapeutic targets and diagnostic markers. Missense mutations are nucleotide substitutions that change an amino acid in a protein, the deleterious effects of these mutations are commonly attributed to their impact on primary amino acid sequence and protein structure. Methods: The method to identify functional SNPs from a pool, containing both functional and neutral SNPs is challenging by experimental protocols. To explore possible relationships between genetic mutation and phenotypic variation, we employed different bioinformatics algorithms like Sorting Intolerant from Tolerant (SIFT), Polymorphism Phenotyping (PolyPhen), and PupaSuite to predict the impact of these amino acid substitutions on protein activity of mismatch repair (MMR) genes causing hereditary nonpolyposis colorectal cancer (HNPCC). Results: SIFT classified 22 of 125 variants (18%) as 'Intolerant. " PolyPhen classified 40 of 125 amino acid substitutions (32%) as "Probably or possibly damaging". The PupaSuite predicted th