Nonsynonymous Single-Nucleotide Polymorphisms of the Human Apoptosis-Related Endonuclease - DNA Fragmentation Factor Beta Polypeptide, Endonuclease G, and Flap Endonuclease-1 - Genes Show a Low Degree of Genetic Heterogeneity

被引：5

作者：

Takeshita, Haruo ^{[1
]}

Fujihara, Junko ^{[1
]}

Ueki, Misuzu ^{[2
]}

Iida, Reiko ^{[3
]}

Koda, Yoshiro ^{[4
]}

Soejima, Mikiko ^{[4
]}

Yuasa, Isao ^{[5
]}

Kato, Hideaki ^{[6
]}

Nakajima, Tamiko ^{[7
]}

Kominato, Yoshihiko ^{[7
]}

Yasuda, Toshihiro ^{[2
]}

机构：

[1] Shimane Univ, Sch Med, Dept Legal Med, Izumo, Shimane 6938501, Japan

[2] Univ Fukui, Fac Med Sci, Div Med Genet & Biochem, Fukui 910, Japan

[3] Univ Fukui, Fac Med Sci, Div Life Sci, Fukui 910, Japan

[4] Kurume Univ, Sch Med, Dept Forens Med & Human Genet, Fukuoka, Japan

[5] Tottori Univ, Grad Sch Med, Dept Legal Med, Tottori 680, Japan

[6] Nagoya City Univ, Grad Sch Med Sci, Dept Forens Med Sci, Nagoya, Aichi, Japan

[7] Gunma Univ, Grad Sch Med, Dept Legal Med, Gunma, Japan

来源：

DNA AND CELL BIOLOGY | 2012年 / 31卷 / 01期

基金：

日本学术振兴会;

关键词：

CASPASE-ACTIVATED DNASE; POTENTIALLY RELEVANT; EXPRESSION ANALYSIS; AUTOIMMUNITY; REPLICATION; MUTATIONS; NUCLEASE; RESIDUES; DISEASE; ONSET;

D O I：

10.1089/dna.2011.1293

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA fragmentation factor beta (DFFB) polypeptide, endonuclease G (EndoG), and Flap endonuclease-1 (FEN-1) are responsible for DNA fragmentation, a hallmark of apoptosis. Although the human homologs of these genes show three, four, and six nonsynonymous single-nucleotide polymorphisms (SNPs), respectively, data on their genotype distributions in populations worldwide are limited. In this context, the objectives of this study were to elucidate the genetic heterogeneity of all these SNPs in wide-ranging populations, and thereby to clarify the genetic background of these apoptosis-related endonucleases in human populations. We investigated the genotype distribution of their SNPs in 13 different populations of healthy Asians, Africans, and Caucasians using novel genotyping methods. Among the 13 SNPs in the 3 genes, only 3 were found to be polymorphic: R196K and K277R in the DFFB gene, and S12L in the EndoG gene. All 6 SNPs in the FEN-1 gene were entirely monoallelic. Although it remains unclear whether each SNP would exert any effect on endonuclease functions, these genes appear to exhibit low degree of genetic heterogeneity with regard to nonsynonymous SNPs. These findings allow us to conclude that human apoptosis-related endonucleases, similarly to other human DNase genes, revealed previously, are well conserved at the protein level during the course of human evolution.

引用

页码：36 / 42

页数：7