Genotyping 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.
Five 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.
The 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.