title: Evaluation of all nonsynonymous single-nucleotide polymorphisms in the gene encoding human deoxyribonuclease I-like 1, possibly implicated in the blocking of endocytosis-mediated foreign gene transfer.
abstract: Many nonsynonymous single-nucleotide polymorphisms (SNPs) in the human deoxyribonuclease I-like 1 (DNase 1L1) gene, possibly implicated in the blocking of endocytosis-mediated foreign gene transfer, have been identified, but only limited population data are available and no studies have evaluated whether such SNPs are functional. Genotyping of all 21 nonsynonymous human DNase 1L1 SNPs was performed in 16 different populations representing three ethnic groups using the PCR-restriction fragment length polymorphism technique. All of the nonsynonymous SNPs, except for SNP p.Val122Ile in Caucasian populations, exhibited a monoallelic distribution in all of the populations. On the basis of alterations in the activity levels resulting from the corresponding amino acid substitutions, two activity-abolishing and four activity-reducing SNPs were confirmed to be functional. Although all of the nonsynonymous SNPs that affected the catalytic activity showed extremely low genetic heterogeneity, it seems plausible that a minor allele of six SNPs producing a loss-of-function or extremely low-activity variant could serve directly as a genetic risk factor for diseases. Especially, the amino acid residues in activity-abolishing SNPs were conserved in animal DNases 1L1. Furthermore, results of phylogenetic analysis suggest that DNase 1L1 might have appeared latest among the DNase I family during the course of molecular evolution.
authors: 1 Division of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui , Fukui, Japan .
authors: Misuzu
authors: M
authors: Ueki
authors: Kaori
authors: K
authors: Kimura-Kataoka
authors: Junko
authors: J
authors: Fujihara
authors: Haruo
authors: H
authors: Takeshita
authors: Reiko
authors: R
authors: Iida
authors: Toshihiro
authors: T
authors: Yasuda
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002384:Catalysis; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D003850:Deoxyribonuclease I / Q000235:genetics*; D004705:Endocytosis / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal / Q000235:genetics*; D005822:Genetic Vectors; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D009124:Muscle Proteins; C097585:DNASE1L1 protein, human; D003850:Deoxyribonuclease I