title: Identification of the functional alleles of the nonsynonymous single-nucleotide polymorphisms potentially implicated in systemic lupus erythematosus in the human deoxyribonuclease I gene.
abstract: In the present study, we have extensively continued our previous investigations of the nonsynonymous single-nucleotide polymorphisms (SNPs) in the human DNase I (DNASE1) gene potentially relevant to systemic lupus erythematosus (SLE); therefore, all of the 58 nonsynonymous SNPs registered in the NCBI dbSNP database could be evaluated and it could be checked as to whether these SNPs might serve as a functional SNP. From a compiled expression analysis of the amino-acid-substituted DNase I corresponding to each of the SNPs, it was possible to sort them into 23 SNPs while not affecting the activity: 12 abolishing it, 14 reducing it, and 9 increasing it. Among a total of 58 nonsynonymous SNPs, only 4 SNPs exhibited genetic polymorphisms in some of the populations examined; a minor allele producing a loss-of-function variant of each SNP was not distributed in 14 different populations derived from three ethnic groups. It could be assumed that a minor allele of these functional SNPs, despite their remarkably low genetic heterogeneity, could directly serve as a genetic risk factor for SLE. Furthermore, among the human DNase family genes, it seems that DNASE1 is able to tolerate the generation of nonsynonymous SNPs, and that the amino-acid substitutions resulting from the SNPs in DNASE1 easily alter the activity.
authors.affiliation: 1 Department of Legal Medicine, Shimane University School of Medicine , Shimane, Japan .
authors.forename: Kaori
authors.initials: K
authors.lastname: Kimura-Kataoka
authors.forename: Misuzu
authors.initials: M
authors.lastname: Ueki
authors.forename: Haruo
authors.initials: H
authors.lastname: Takeshita
authors.forename: Junko
authors.initials: J
authors.lastname: Fujihara
authors.forename: Reiko
authors.initials: R
authors.lastname: Iida
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kawai
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yasuda
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003850:Deoxyribonuclease I / Q000235:genetics*; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I