Global genetic analysis of all single nucleotide polymorphisms in exons of the human deoxyribonuclease I-like 3 gene and their effect on its catalytic activity
Global genetic analysis of all single nucleotide polymorphisms in exons of the human deoxyribonuclease I-like 3 gene and their effect on its catalytic activity
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人脱氧核糖核酸酶I-like 3基因外显子所有单核苷酸多态性的整体遗传分析及其对其催化活性的影响
DOI：
10.1002/elps.201100064
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发表时间：
2011
期刊：
影响因子：
2.9
通讯作者：
Yasuda T
中科院分区：
文献类型：
--
作者：
Ueki M;Fuiihara J;Takeshita H;Kimura-Kataoka K;Iida R;Yuasa I;Kato H;Yasuda T
脱氧核糖核酸酶（DNA酶）被认为与自身免疫性疾病的病理生理学有关。在编码人类 DNase I 样 3 (DNase 1L3)（DNase I 家族成员）的 DNASE1L3 基因中，仅检查了两个非同义（R178 H 和 R206C）单核苷酸多态性 (SNP) [Ueki et al., Clin.奇姆。 Acta2009,407, 20–24]。除了 R206C 和 R178H 之外，在 DNASE1L3 中还鉴定出了其他三个非同义（G82R、K96N 和 I243M）和四个同义（S17S、T84T、R92R 和 A181A）SNP。我们使用新设计的基因分型方法调查了全球 8 个亚洲人、3 个非洲人和 3 个白种人人群的基因外显子中所有这些 SNP 的分布。 SNP T84T 在所有人群中均表现出多态性，R92R 在 3 个非洲人群和 3 个白种人人群中均表现出多态性； R206C 仅分布于白种人群体中。相反，DNASE1L3中的5个SNP（S17S、G82R、K96N、A181A和I243M）中没有发现次要等位基因。一般来说，DNase 1L3基因在外显子SNP方面表现出相对较低的遗传多样性。当检查 SNP 引起的氨基酸/核苷酸取代对 DNase 1L3 活性的影响时，没有同义 SNP 对 DNase 1L3 活性产生任何影响，而在非同义 SNP 中，SNP G82R 降低了酶的活性，与 R206C 类似。这些发现使我们可以假设，虽然只有 R206 以白种人特有的方式表现出多态性，但至少 DNASE1L3 中的 SNP G82R 和 R206C 可能是自身免疫性疾病的潜在危险因素。
Deoxyribonucleases (DNases) have been suggested to be implicated in the pathophysiology of autoimmune diseases. In theDNASE1L3gene encoding human DNase I‐like 3 (DNase 1L3), a member of the DNase I family, only two non‐synonymous (R178 H and R206C) single nucleotide polymorphisms (SNPs) have been examined [Ueki et al.,Clin. Chim. Acta2009,407, 20–24]. Three other non‐synonymous (G82R, K96N, and I243M) and four synonymous (S17S, T84T, R92R, and A181A) SNPs, in addition to R206C and R178H, have been identified inDNASE1L3. We investigated the distribution of all these SNPs in exons of the gene in eight Asian, three African, and three Caucasian populations worldwide using newly devised genotyping methods. SNP T84T showed polymorphism in all the populations, and R92R was polymorphic in the three African and three Caucasian populations; R206C was distributed only in Caucasian populations. In contrast, no minor allele was found in five SNPs (S17S, G82R, K96N, A181A, and I243M) inDNASE1L3.Generally, theDNase 1L3gene shows relatively low genetic diversity with regard to exonic SNPs. When the effect of amino acid/nucleotide substitutions resulting from the SNPs on DNase 1L3 activity was examined, none of the synonymous SNPs had any effect on the DNase 1L3 activity, whereas among non‐synonymous SNPs, SNP G82R diminished the activity of the enzyme, being similar to R206C. These findings permit us to assume that, although only R206 exhibits polymorphisms in a Caucasian‐specific manner, at least SNPs G82R and R206C inDNASE1L3might be potential risk factors for autoimmune disease.