Computational prediction of the effects of non-synonymous single nucleotide polymorphisms in human DNA repair genes

Non-synonymous single nucleotide polymorphisms (nsSNPs) represent common genetic variation that alters encoded amino acids in proteins. All nsSNPs may potentially affect the structure or function of expressed proteins and could therefore have an impact on complex diseases. In an effort to evaluate the phenotypic effect of all known nsSNPs in human DNA repair genes, we have characterized each polymorphism in terms of different functional properties. The properties are computed based on amino acid characteristics (e.g. residue volume change); position-specific phylogenetic information from multiple sequence alignments and from prediction programs such as SIFT (Sorting Intolerant From Tolerant) and PolyPhen (Polymorphism Phenotyping). We provide a comprehensive, updated list of all validated nsSNPs from dbSNP (public database of human single nucleotide polymorphisms at National Center for Biotechnology Information, USA) located in human DNA repair genes. The list includes repair enzymes, genes associated with response to DNA damage as well as genes implicated with genetic instability or sensitivity to DNA damaging agents. Out of a total of 152 genes involved in DNA repair, 95 had validated nsSNPs in them. The fraction of nsSNPs that had high probability of being functionally significant was predicted to be 29.6% and 30.9%, by SIFT and PolyPhen respectively. The resulting list of annotated nsSNPs is available online (http://dna.uio.no/repairSNP), and is an ongoing project that will continue assessing the function of coding SNPs in human DNA repair genes.