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Evaluation of all non‐synonymous single nucleotide polymorphisms ( SNP s) in the genes encoding human deoxyribonuclease I and I‐like 3 as a functional SNP potentially implicated in autoimmunity
Author(s) -
Ueki Misuzu,
KimuraKataoka Kaori,
Takeshita Haruo,
Fujihara Junko,
Iida Reiko,
Sano Rie,
Nakajima Tamiko,
Kominato Yoshihiko,
Kawai Yasuyuki,
Yasuda Toshihiro
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12608
Subject(s) - single nucleotide polymorphism , genetics , biology , snp , gene , genotype , loss of heterozygosity , allele , deoxyribonuclease i , snp genotyping , base sequence
The objectives of this study were to evaluate all the non‐synonymous single nucleotide polymorphisms ( SNP s) in the DN ase I and DN ase I‐like 3 (1L3) genes potentially implicated in autoimmune diseases as a functional SNP in terms of alteration of the activity levels. We examined the genotype distributions of the 32 and 20 non‐synonymous SNP s in DNASE 1 and DNASE 1L3 , respectively, in three ethnic groups, and the effect of these SNP s on the DN ase activities. Among a total of 44 and 25 SNP s including those characterized in our previous studies [Yasuda et al ., Int J Biochem Cell Biol 42 (2010) 1216–1225; Ueki et al. Electrophoresis 32 (2012) 1465–1472], only four and one, respectively, exhibited genetic heterozygosity in one or all of the ethnic groups examined. On the basis of alterations in the activity levels resulting from the corresponding amino acid substitutions, 11 activity‐abolishing and 11 activity‐reducing SNP s in DNASE 1 and two activity‐abolishing and five activity‐reducing SNP s in DNASE 1L3 were confirmed as a functional SNP . Phylogenetic analysis showed that all of the amino acid residues in activity‐abolishing SNP s were completely or well conserved in animal DN ase I and 1L3 proteins. Although almost all non‐synonymous SNP s in both genes that affected the catalytic activity showed extremely low genetic heterogeneity, it seems plausible that a minor allele of 13 activity‐abolishing SNP s producing a loss‐of‐function variant in both the DN ase genes would be a direct genetic risk factor for autoimmune diseases. These findings may have clinical implications in relation to the prevalence of autoimmune diseases.