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
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
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人类凋亡相关内切核酸酶-DNA 片段因子 β 多肽、内切核酸酶 G 和 Flap 内切核酸酶 1 基因的非同义单核苷酸多态性显示出较低程度的遗传异质性
DOI：
10.1089/dna.2011.1293
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发表时间：
2012
影响因子：
3.1
通讯作者：
H.Takeshita
中科院分区：
文献类型：
--
作者：
Poudel-Tandukar K;Nanri A;Matsushita Y;Sasaki S;Ohta M;Sato M;Mizoue T;Soichiro Usui;新開省二;H.Takeshita
DNA片段化因子β（DFFB）多肽、核酸内切酶G（EndoG）和Flap核酸内切酶-1（FEN-1）负责DNA片段化，DNA片段化是细胞凋亡的标志。虽然这些基因的人类同源物分别显示出三个、四个和六个非同义的单核苷酸多态性（SNP），但它们在全球人群中的基因型分布数据有限。在此背景下，本研究的目的是阐明所有这些SNP在广泛人群中的遗传异质性，从而阐明这些糖尿病相关核酸内切酶在人群中的遗传背景。我们使用新的基因分型方法研究了13个不同健康亚洲人、非洲人和高加索人群体中SNP的基因型分布。在3个基因的13个SNPs中，只有3个是多态的，即DFFB基因的R196 K和K277 R，EndoG基因的S12 L。FEN-1基因的6个SNPs均为单等位基因。虽然目前还不清楚每个SNP是否会对核酸内切酶功能产生任何影响，但这些基因似乎表现出较低程度的遗传异质性。这些研究结果使我们能够得出结论，人类乳腺癌相关的核酸内切酶，类似于其他人类DNA酶基因，揭示了以前，在人类进化过程中，在蛋白质水平上是很保守的。
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 theDFFBgene, and S12L in theEndoGgene. All 6 SNPs in theFEN-1gene 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.