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Seven nonsynonymous SNP s in the gene encoding human deoxyribonuclease II may serve as a functional SNP potentially implicated in autoimmune dysfunction
Author(s) -
KimuraKataoka Kaori,
Ueki Misuzu,
Takeshita Haruo,
Fujihara Junko,
Iida Reiko,
Kato Hideaki,
Yasuda Toshihiro
Publication year - 2013
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201300399
Subject(s) - nonsynonymous substitution , single nucleotide polymorphism , biology , snp genotyping , genetics , snp , genotyping , population , gene , minor allele frequency , allele frequency , allele , genotype , medicine , genome , environmental health
Many nonsynonymous SNP s in the human DN ase II gene ( DNASE2 ), potentially relevant to autoimmunity in conditions such as rheumatoid arthritis, have been identified, but only limited population data are available and no studies have evaluated whether such SNP s are functional. Genotyping of all the 15 nonsynonymous human DN ase II SNP s was performed in three ethnic groups including 16 different populations using the PCR ‐restriction fragment length polymorphism technique. A series of constructs corresponding to each SNP was examined. Fifteen nonsynonymous SNP s in the gene, except for p.Val206Ile in a K orean population, exhibited a mono‐allelic distribution in all of the populations. On the basis of alterations in the activity levels resulting from the corresponding amino acid substitutions, four activity‐abolishing and five activity‐reducing SNP s were confirmed to be functional. The amino acid residues in activity‐abolishing SNP s were conserved in animal DN ase II. All the nonsynonymous SNP s that affected the catalytic activity of human DN ase II showed extremely low genetic heterogeneity. However, a minor allele of seven SNP s producing a loss‐of‐function or extremely low activity‐harboring variant could serve as a genetic risk factor for autoimmune dysfunction. These functional SNP s in DNASE 2 may have clinical implications in relation to the prevalence of autoimmune diseases.