APOBEC and ADAR deaminases may cause many single nucleotide polymorphisms curated in the OMIM database

Publication date: Available online 22 June 2018 Source:Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Author(s): Robyn A. Lindley, Nathan E. Hall Cytosine and adenosine deamination events (DNA, RNA substrates) account for most codon-context Targeted Somatic Mutation (TSM) patterns observed in immunoglobulin (Ig) somatic hypermutation (SHM), and in cancer exomes following Ig-SHM-like responses. TSM refers to the process of somatic mutagenesis involving deamination events that results on a dominant type of mutation (e.g., C-to-T), and co-incident at a particular motif (e.g., WRC), and preferentially targeting the first, second or third nucleotide position within the mutated codon (e.g. MC1, MC2 or MC3, read 5-prime to 3-prime). It is now widely accepted that if left uncorrected, the accumulation of uncorrected TSMs involving the deaminases, may lead to a diagnosis of cancer or other degenerative disease. Our hypothesis is that many missense, nonsense and synonymous single nucleotide polymorphisms (SNPs) associated with clinically significant diseases may have arisen in the population by similar highly targeted deamination events. The OMIM database was searched for disease-associated SNPs on the X chromosome, and for all chromosomes. The nucleotide substitution patterns for disease-associated SNPs were analyzed by the TSM method to identify the likely deaminase source for C-to-U (C-to-T/G-to-A) and A-to-I (A-to-G/T-to-C) derived gene mutations preferen...

Source: Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis - June 22, 2018 Category: Cytology Source Type: research