Chen J, Yu Z, Ford B N, Brackley M E, Haesevoets R J, Khaidakov M, Glickman B W
Centre for Environmental Health and the Department of Biology, University of Victoria, Victoria, British Columbia, Canada.
Environ Mol Mutagen. 2000;36(3):228-34.
A significant fraction of human cancers are thought to have a genetic component and several lines of evidence suggest that deficiencies in DNA repair may be a contributing factor. Little is known, however, about the frequency and distribution of variants of DNA repair genes in the general human population. The protein truncation test (PTT) was used to screen 136 healthy volunteers for protein-truncating variants of 10 DNA repair genes: APE, CDK7, ERCC1, WAF1, HOGG1, MGMT, POLB, UNG, HAAG, and CCNH. This sample consisted of 41males (30%) and 95 females (70%) with an average age of 25.3 years, ranging from 17 to 60 years of age. No truncating mutations were found in the 10 genes examined in any of the subjects. The 95% confidence interval for a proportion of 0 over the 272 alleles examined per locus is 0-0.01. The calculated frequency of truncating mutations in each of these genes, among the general population, is thus less than 1%. Among the 10 genes tested in 136 people, a single sample had no PCR product for HAAG, even though PCR products were obtained on all other genes. Total RNA dot hybridization confirmed the presence of HAAG mRNA transcripts in this sample. Despite identification of this single DNA repair variant, these results indicate a low frequency of truncating mutations in DNA repair genes in the general population.
人们认为很大一部分人类癌症具有遗传成分，并且有几条证据表明DNA修复缺陷可能是一个促成因素。然而，对于普通人群中DNA修复基因变体的频率和分布知之甚少。蛋白质截短试验（PTT）用于筛查136名健康志愿者，以检测10个DNA修复基因（APE、CDK7、ERCC1、WAF1、HOGG1、MGMT、POLB、UNG、HAAG和CCNH）的蛋白质截短变体。该样本包括41名男性（30%）和95名女性（70%），平均年龄为25.3岁，年龄范围为17至60岁。在所检查的任何受试者的10个基因中均未发现截短突变。每个位点检测的272个等位基因中比例为0的95%置信区间为0 - 0.01。因此，在普通人群中，这些基因中每个基因的截短突变计算频率均小于1%。在136人检测的10个基因中，有一个样本的HAAG没有PCR产物，尽管所有其他基因都获得了PCR产物。总RNA点杂交证实该样本中存在HAAG mRNA转录本。尽管鉴定出了这一单一的DNA修复变体，但这些结果表明普通人群中DNA修复基因的截短突变频率较低。
