Mutational pattern and frequency of induced nucleotide changes in mouse ENU mutagenesis.
Mutational pattern and frequency of induced nucleotide changes in mouse ENU mutagenesis.
复制标题
小鼠ENU诱变中诱导核苷酸变化的突变模式和频率。
DOI：
10.1186/1471-2199-8-52
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发表时间：
2007-06-20
影响因子：
--
通讯作者：
Gondo Y
中科院分区：
文献类型：
--
作者：
Takahasi KR;Sakuraba Y;Gondo Y
随着诱变研究中基于序列的方法的出现，现在可以直接评估多种生物体实验诱导的 DNA 序列变化的全基因组模式。为了更全面地了解小鼠 ENU 诱变中固有的突变偏向，本研究描述了对从 ENU 诱变小鼠的基于序列的筛选中获得的诱导突变模式的详细评估。基于大规模筛选数据，我们得出了对小鼠种系中 ENU 诱导的碱基替换突变的核苷酸特异性模式和频率的基于序列的估计，然后将其与小鼠编码序列中的密码子使用模式相结合，以推断通过 ENU 诱变获得的氨基酸变化谱。我们检测到表型筛选与基于序列筛选的突变模式之间存在统计学上的显着差异，这可能反映了不同氨基酸替换引起的不同表型效应。我们还证明，突变表现出强烈的链不对称性，并且这种不平衡是由转录产生的，很可能是种系中转录偶联 DNA 修复的副产品。结果清楚地说明了 ENU 诱导突变的偏差性质。我们预计，在设计基于序列的筛选策略以生成在特定位点含有氨基酸变体的突变小鼠品系时，精确了解突变模式和诱导核苷酸变化的频率将具有实际意义。更一般地说，通过加强明确定义的基因组区域中实验诱导突变的收集，基于序列的诱变研究将进一步阐明诱变和修复机制的分子基础，这些机制优先产生某一类突变变化。
With the advent of sequence-based approaches in the mutagenesis studies, it is now possible to directly evaluate the genome-wide pattern of experimentally induced DNA sequence changes for a diverse array of organisms. To gain a more comprehensive understanding of the mutational bias inherent in mouse ENU mutagenesis, this study describes a detailed evaluation of the induced mutational pattern obtained from a sequence-based screen of ENU-mutagenized mice. Based on a large-scale screening data, we derive the sequence-based estimates of the nucleotide-specific pattern and frequency of ENU-induced base replacement mutation in the mouse germline, which are then combined with the pattern of codon usage in the mouse coding sequences to infer the spectrum of amino acid changes obtained by ENU mutagenesis. We detect a statistically significant difference between the mutational patterns in phenotype- versus sequence-based screens, which presumably reflects differential phenotypic effects caused by different amino acid replacements. We also demonstrate that the mutations exhibit strong strand asymmetry, and that this imbalance is generated by transcription, most likely as a by-product of transcription-coupled DNA repair in the germline. The results clearly illustrate the biased nature of ENU-induced mutations. We expect that a precise understanding of the mutational pattern and frequency of induced nucleotide changes would be of practical importance when designing sequence-based screening strategies to generate mutant mouse strains harboring amino acid variants at specific loci. More generally, by enhancing the collection of experimentally induced mutations in unambiguously defined genomic regions, sequence-based mutagenesis studies will further illuminate the molecular basis of mutagenic and repair mechanisms that preferentially produce a certain class of mutational changes over others.
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影响因子：
3.3
作者：
Concepcion, D;Seburn, KL;Hamilton, BA
通讯作者：
Hamilton, BA
影响因子：
7
作者：
Dahary, D;Elroy-Stein, O;Sorek, R
通讯作者：
Sorek, R
DOI：
10.1016/0027-5107(90)90173-2
发表时间：
1990-07-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
BERANEK, DT
通讯作者：
BERANEK, DT
影响因子：
2.5
作者：
Beier, DR
通讯作者：
Beier, DR
影响因子：
30.8
作者：
Chen, YJ;Yee, D;Magnuson, T
通讯作者：
Magnuson, T