title: Genetic and expression analysis of all non-synonymous single nucleotide polymorphisms in the human deoxyribonuclease I-like 1 and 2 genes.
abstract: Members of the human DNase I family, DNase I-like 1 and 2 (DNases 1L1 and 1L2), with physiological role(s) other than those of DNase I, possess three and one non-synonymous SNPs in the genes, respectively. However, only limited population data are available, and the effect of these SNPs on the catalytic activity of the enzyme remains unknown. Genotyping of all the non-synonymous SNPs was performed in three ethnic groups including six different populations using the PCR-RFLP method newly developed. Asian and African groups including Japanese, Koreans, Ghanaians and Ovambos were typed as a single genotype at each SNP, but polymorphism at only SNP V122I in DNase 1L1 was found in Caucasian groups including Germans and Turks; thus a Caucasian-specific allele was identified. The DNase 1L1 and 1L2 genes show relatively low genetic diversity with regard to these non-synonymous SNPs. The level of activity derived from the V122I, Q170H and D227A substituted DNase 1L1 corresponding to SNPs was similar to that of the wild-type, whereas replacement of the Asp residue at position 197 in the DNase 1L2 protein with Ala, corresponding to SNP D197A, reduced its activity greatly. Thus, SNP V122I in DNase 1L1 exhibiting polymorphism exerts no effect on the catalytic activity, and furthermore SNP D197A in DNase 1L2, affecting its catalytic activity, shows no polymorphism. These findings permit us to postulate that the non-synonymous SNPs identified in the DNase 1L1 and 1L2 genes may exert no influence on the activity levels of DNases 1L1 and 1L2 in human populations.
authors.affiliation: Division of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Misuzu
authors.initials: M
authors.lastname: Ueki
authors.forename: Junko
authors.initials: J
authors.lastname: Fujihara
authors.forename: Haruo
authors.initials: H
authors.lastname: Takeshita
authors.forename: Kaori
authors.initials: K
authors.lastname: Kimura-Kataoka
authors.forename: Reiko
authors.initials: R
authors.lastname: Iida
authors.forename: Tamiko
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kominato
authors.forename: Isao
authors.initials: I
authors.lastname: Yuasa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yasuda
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D016009:Chi-Square Distribution; D003850:Deoxyribonuclease I / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; C097585:DNASE1L1 protein, human; C107519:DNASE1L2 protein, human; D003850:Deoxyribonuclease I