Genetic and expression analysis of all seven non-synonymous single nucleotide polymorphisms in the human deoxyribonuclease II gene, with potential relevance to autoimmunity
Genetic and expression analysis of all seven non-synonymous single nucleotide polymorphisms in the human deoxyribonuclease II gene, with potential relevance to autoimmunity
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人类脱氧核糖核酸酶 II 基因中所有七个非同义单核苷酸多态性的遗传和表达分析，与自身免疫具有潜在相关性
DOI：
10.1016/j.cca.2009.10.013
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
T. Yasuda
中科院分区：
文献类型：
--
作者：
M. Ueki;H. Takeshita;T. Yasuda
研究背景人类DNA酶II基因中的几个非同义SNPs，可能与自身免疫相关，已被鉴定，但只有有限的人群数据可用。此外，这些SNPs的催化活性的酶的影响仍然unknowed. METHODS进行基因分型的所有非同义SNPs的3个种族，包括6个不同的人群，使用PCR-RFLP技术的健康受试者。在COS-7细胞中表达了一系列对应于每个SNP的突变体，并测量了其活性。包括日本人、德国人、土耳其人、加纳人和Ovambos人在内的五个群体在每个SNP处被分型为单一基因型，但韩国人没有。来自A58 del，V284 M，R298 L和Q322 Term的次要等位基因的构建体表现出极低或几乎没有activity. CONCLUSION的DNase II基因显示相对较低的遗传多样性，这些非同义的SNPs，这表明该酶已被很好地保守。V284 M处的次要等位基因在数据库中以0.013的频率分布，并且杂合子的DNA酶II活性水平低于具有主要纯合子的个体中的水平似乎是合理的。我们的研究结果可能有临床意义的自身免疫性疾病的患病率。
BACKGROUNDSeveral non-synonymous SNPs in the human DNase II gene, potentially relevant to autoimmunity, have been identified, but only limited population data are available. Also, the effects of these SNPs on the catalytic activity of the enzyme remain unknown.METHODSGenotyping of all the non-synonymous SNPs was performed in healthy subjects of 3 ethnic groups including 6 different populations using the PCR-RFLP technique. A series of mutants corresponding to each SNP was expressed in COS-7 cells and its activity was measured.RESULTSFive of the populations, including Japanese, Germans, Turks, Ghanaians and Ovambos, were typed as a single genotype at each SNP, but Koreans were not. Constructs derived from minor alleles at A58del, V284M, R298L and Q322Term exhibited drastically low or almost no activity.CONCLUSIONThe DNase II gene shows relatively low genetic diversity with regard to these non-synonymous SNPs, suggesting that the enzyme has been well conserved. A minor allele at V284M is distributed with a frequency of 0.013 in the database, and it seems plausible that levels of DNase II activity for the heterozygote are lower than those in individuals with the predominant homozygote. Our results may have clinical implications in relation to the prevalence of autoimmune diseases.