title: Investigating the role of site specific synonymous variation in disease association studies.
abstract: Synonymous codon changes may not always be neutral indicating their significance in disease association studies, which is almost always overlooked. Synonymous substitutions may affect protein-folding rates leading to protein misfolding and aggregation. Genome wide analysis of 2301 mitochondrial genomes is performed to evaluate the significance of synonymous codons in disease association studies. The analysis revealed usage of rare codons at several sites in mitochondrial genes with rare codon usage higher for hydrophobic amino acids. The analysis suggests that variation data in association studies should be analyzed using site-specific codon usage values to infer the potential phenotypic impact of synonymous changes.
authors.affiliation: Open Source Drug Discovery Unit, Council of Scientific and Industrial Research (CSIR), Delhi 110001, India. Electronic address: anshub@osdd.net.
authors.forename: Anshu
authors.initials: A
authors.lastname: Bhardwaj
mesh_terms: D003062:Codon; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D017354:Point Mutation
chemical_list: D003062:Codon
keywords: Association studies; Mitochondrial DNA; Mitochondrial diseases; Protein folding; Rare codon; Translation