IMPACT OF THE MOLECULAR-SPECTRUM OF MUTATIONAL LESIONS ON ESTIMATES OF GERMINAL GENE-MUTATION RATES

被引:20
作者
MOHRENWEISER, H
机构
[1] Biology and Biotechnology Research Program L-452, Lawrence Livermore National Laboratory, Livermore
来源
MUTATION RESEARCH | 1994年 / 304卷 / 01期
关键词
NUCLEOTIDE SUBSTITUTIONS; MOLECULAR SPECTRUM; MUTATIONAL LESIONS; GERMINAL GENE-MUTATION RATES; GENE-MUTATION RATES; MUTATION RATES;
D O I
10.1016/0027-5107(94)90322-0
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Review of the molecular characteristics of the variants identified at a series of disease loci suggests significant differences among loci in the relative frequency of nucleotide substitutions versus more complex events such as deletions. Some common features are repeatedly observed in each class of variant. For example, a high proportion of the nucleotide substitutions involve transitions of deoxycytidine and are suggested to result from deamination of cytosine at 5-methyl-CpG sites. Similarily, deletions of three or fewer nucleotides are relatively common in the non-nucleotide substitution class and these deletions are often associated with a seven-nucleotide core sequence. A significant fraction of the larger deletions and rearrangements may be associated with repetitive elements. Many of the deletion events do not appear to involve a chromosomal recombination mechanism. Mechanisms involving transcription slippage and chromatid exchange have been suggested as possible alternative mechanisms for generating deletion events. The spectrum of mutational events identified, e.g. nucleotide substitutions versus deletions, differs between loci and is probably a reflection of both the gene structure and the selective pressure to generate a disease phenotype. This locus specificity (at both the biological and molecular level) would appear to have significant potential to compromise estimates of increases in the gene germinal mutation rate following exposure to mutagenic agents.
引用
收藏
页码:119 / 137
页数:19
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