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

采用PCR-RFLP和多重单碱基延伸技术，对3个种族15个群体的1,559名健康受试者进行所有非同义SNPs的基因分型。其中，R-21 S、Y 95 S、G105 R和Q222 R四个SNP位点以及同义SNP L186 L在全部或部分群体中具有多态性。亚洲组显示这些SNP的遗传多样性相对较低，而非洲组具有最高的多样性。Q222 R多态性的分布模式分为三个民族。与野生型相比，来自SNP R-21 S、G105 R、P132 A和P197 S的氨基酸取代的DNA酶I形式的活性水平显著较高;多态性SNP R-21 S（非洲人和墨西哥人）和G105 R（非洲人）产生了高活性的DNA酶I同种型。另一方面，来自Q35 H、R85 G、V89 M、C209 Y、Q222 R和A224 P的活性水平显著低，但这些SNP（除了Q222 R）不分布于所检查的任何群体中。然而，由于这些SNP可能产生潜在的低水平的体内DNA酶I活性，每个SNP中的次要等位基因将作为自身免疫性疾病的遗传风险因素。因此，关于DNA酶1中非同义SNPs的全球分布以及相应氨基酸取代对活性水平的影响的信息将为阐明DNA酶I与疾病之间的可能关系提供遗传基础。

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.