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The study of functional polymorphism within the deoxyribonuclease I gene associated with disease.

脱氧核糖核酸酶 I 基因内与疾病相关的功能多态性的研究。

基本信息

批准号：
19209025
负责人：
TAKESHITA Haruo
金额：
$ 21.38万
依托单位：
Shimane University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19209025/
关键词：
DNase 疾患感受性遺伝子 DNase I 心筋梗塞 DNASE1*1 DNASE1*2 遺伝的多型形質多型 DNASE1^*1 DNASE1^*2 DNASE1 癌民族頻度分布 Database 遺伝的多型

项目摘要

Using both the PCR-RFLP and multiplex single base extension techniques, genotyping of all the non-synonymous SNPs was performed in healthy subjects (n=1,559) of three ethnic groups including 15 populations. Among them, only four SNPs, R-21S, Y95S, G105R, and Q222R, together with the synonymous SNP L186L, were polymorphic in all or some populations. The Asian group showed a relatively low genetic diversity of these SNPs, whereas the African group had the highest diversity. The distribution pattern of the common SNP Q222R was classified into three ethnic groups. Activity levels of the amino acid-substituted DNase I forms derived from SNPs R-21S, G105R, P132A, and P197S were significantly high compared with that of the wild type; the polymorphic SNPs R-21S (Africans and Mexicans) and G105R (Africans) gave rise to a high activity-harboring DNase I isoform. On the other hand, activity levels from Q35H, R85G, V89M, C209Y, Q222R, and A224P were significantly low, but these SNPs, except Q222R, were not distributed in any of the populations examined. However, since these SNPs may produce potentially low levels of in vivo DNase I activity, a minor allele in each SNP will be served as a genetic risk factor for autoimmune diseases. Therefore, information on the worldwide distribution of non-synonymous SNPs in DNASE1 and the effects of the corresponding amino acid substitution on the activity levels will provide a genetic basis for the clarification of a possible relationship between DNase I and diseases.

应用聚合酶链式反应-限制性片段长度多态性和多重单碱基延伸技术，对15个群体、1,559名健康受试者的非同义SNPs进行了基因分型。其中，仅有R-21S、Y95S、G105R和Q222R四个SNP以及同义的SNP L186L在全部或部分群体中具有多态。亚洲群体表现出相对较低的SNPs遗传多样性，而非洲群体具有最高的多样性。常见SNP Q222R的分布模式可分为三个民族。来自SNPs R-21S、G105R、P132A和P197S的氨基酸取代的DNase I亚型的活性水平显著高于野生型，SNPs R-21S(非洲人和墨西哥人)和G105R(非洲人)的多态导致了具有高活性的DNase I亚型。另一方面，Q35H、R85G、V89M、C209Y、Q222R和A224P的SNP活性水平显著较低，但除Q222R外，这些SNP均未在所研究的任何群体中分布。然而，由于这些SNP可能在体内产生潜在的低水平的DNase I活性，每个SNP中的一个微小等位基因将被用作自身免疫性疾病的遗传风险因素。因此，有关DNase1中非同义SNPs在全球的分布以及相应的氨基酸替换对活性水平的影响的信息将为阐明DNase1与疾病之间的可能关系提供遗传学基础。

项目成果

期刊论文数量（122）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

8-hydroxy-2'-deoxyguanosine (8-OHdG) as a possible marker of arsenic poisoning : a clinical case study on the relationship between concentrations of 8-OHdG and each arsenic compound in urine of an acute promyelocytic leukemia patient being treated with ar

8-羟基-2-脱氧鸟苷（8-OHdG）作为砷中毒的可能标志物：关于接受砷治疗的急性早幼粒细胞白血病患者尿液中8-OHdG浓度与每种砷化合物之间关系的临床案例研究

DOI：
发表时间：
2009
期刊：
Forensic Toxicol. 27
影响因子：
0
作者：
Fujihara J;Agusa T;Tanaka J;Fujii Y;Moritani T;Hasegawa M;Iwata H;Tanabe S;Takeshita H.
通讯作者：
Takeshita H.

Allele frequencies for 15 STR loci in Ovambo population using AmpFlSTR^R Identifiler Kit.

使用 AmpFlSTR^R Identifiler 试剂盒得出 Ovambo 群体中 15 个 STR 位点的等位基因频率。