Division of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Electrophoresis. 2010 Jun;31(12):2063-9. doi: 10.1002/elps.201000002.
Members of the human DNase I family, DNase I-like 1 and 2 (DNases 1L1 and 1L2), with physiological role(s) other than those of DNase I, possess three and one non-synonymous SNPs in the genes, respectively. However, only limited population data are available, and the effect of these SNPs on the catalytic activity of the enzyme remains unknown. Genotyping of all the non-synonymous SNPs was performed in three ethnic groups including six different populations using the PCR-RFLP method newly developed. Asian and African groups including Japanese, Koreans, Ghanaians and Ovambos were typed as a single genotype at each SNP, but polymorphism at only SNP V122I in DNase 1L1 was found in Caucasian groups including Germans and Turks; thus a Caucasian-specific allele was identified. The DNase 1L1 and 1L2 genes show relatively low genetic diversity with regard to these non-synonymous SNPs. The level of activity derived from the V122I, Q170H and D227A substituted DNase 1L1 corresponding to SNPs was similar to that of the wild-type, whereas replacement of the Asp residue at position 197 in the DNase 1L2 protein with Ala, corresponding to SNP D197A, reduced its activity greatly. Thus, SNP V122I in DNase 1L1 exhibiting polymorphism exerts no effect on the catalytic activity, and furthermore SNP D197A in DNase 1L2, affecting its catalytic activity, shows no polymorphism. These findings permit us to postulate that the non-synonymous SNPs identified in the DNase 1L1 and 1L2 genes may exert no influence on the activity levels of DNases 1L1 and 1L2 in human populations.
人类 DNase I 家族的成员，DNase I 样 1 和 2（DNases 1L1 和 1L2），除了具有 DNase I 的生理作用外，它们的基因分别具有三个和一个非同义 SNP。然而，仅有有限的人群数据可用，并且这些 SNP 对酶的催化活性的影响仍然未知。使用新开发的 PCR-RFLP 方法，在包括六个不同人群的三个种族群体中对所有非同义 SNP 进行了基因分型。亚洲和非洲群体（包括日本人、韩国人、加纳人和奥万博人）在每个 SNP 处均为单一基因型，但在 DNase 1L1 中的 SNP V122I 处发现了仅在白种人群体（包括德国人和土耳其人）中的多态性；因此鉴定了一个白种人特异性等位基因。DNase 1L1 和 1L2 基因在这些非同义 SNP 方面显示出相对较低的遗传多样性。来自对应于 SNP 的 V122I、Q170H 和 D227A 取代的 DNase 1L1 的活性水平与野生型相似，而对应于 SNP D197A 时将 DNase 1L2 蛋白中位置 197 的天冬氨酸残基替换为丙氨酸，则大大降低了其活性。因此，表现出多态性的 DNase 1L1 中的 SNP V122I 对催化活性没有影响，并且进一步地，影响其催化活性的 DNase 1L2 中的 SNP D197A 没有多态性。这些发现使我们假设在 DNase 1L1 和 1L2 基因中鉴定的非同义 SNP 可能不会对人类群体中 DNase 1L1 和 1L2 的活性水平产生影响。
