Genetic and expression analysis of all 7 non-synonymous single nucleotide polymorphisms in the human deoxyribonuclease II gene, with potential relevance to autoimmunity

BackgroundSeveral non-synonymous SNPs in the human DNase II gene, potentially relevant to autoimmunity, have been identified, but only limited population data are available. Also, the effects of these SNPs on the catalytic activity of the enzyme remain unknown.MethodsGenotyping of all the non-synonymous SNPs was performed in healthy subjects of 3 ethnic groups including 6 different populations using the PCR-RFLP technique. A series of mutants corresponding to each SNP was expressed in COS-7 cells and its activity was measured.ResultsFive of the populations, including Japanese, Germans, Turks, Ghanaians and Ovambos, were typed as a single genotype at each SNP, but Koreans were not. Constructs derived from minor alleles at A58del, V284M, R298L and Q322Term exhibited drastically low or almost no activity.ConclusionThe DNase II gene shows relatively low genetic diversity with regard to these non-synonymous SNPs, suggesting that the enzyme has been well conserved. A minor allele at V284M is distributed with a frequency of 0.013 in the database, and it seems plausible that levels of DNase II activity for the heterozygote are lower than those in individuals with the predominant homozygote. Our results may have clinical implications in relation to the prevalence of autoimmune diseases.