Analysis of Multiple Ethyl Methanesulfonate-Mutagenized Caenorhabditis elegans Strains by Whole-Genome Sequencing
Analysis of Multiple Ethyl Methanesulfonate-Mutagenized Caenorhabditis elegans Strains by Whole-Genome Sequencing
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DOI：
10.1534/genetics.110.116319
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发表时间：
2010-06-01
期刊：
影响因子：
3.3
通讯作者：
Hobert, Oliver
中科院分区：
文献类型：
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作者：
Sarin, Sumeet;Bertrand, Vincent;Hobert, Oliver
显示特定突变表型的生物体的全基因组测序（WGS）是鉴定大量生物过程的遗传决定因素的有力方法。我们以前已经验证了这种方法的可行性，通过确定一个点突变的位点负责一个特定的表型，观察到在甲磺酸乙酯（EMS）诱变秀丽隐杆线虫菌株。在这里，我们描述了17个EMS诱变基因组的全基因组突变谱，评估与生物信息学管道，称为MAQGene。令人惊讶的是，我们发现，虽然异交诱变菌株确实减少了突变的总数，但即使在异交菌株中仍然观察到惊人的突变负荷。在建立基因型和表型之间的因果关系时，必须考虑到这种遗传复杂性。即使是无意的，这里描述的17个测序菌株提供了近1000个基因中的等位基因变体的资源，包括62个过早终止密码子，其代表了将进一步用于C. elegans社区研究基因功能。
Whole-genome sequencing (WGS) of organisms displaying a specific mutant phenotype is a powerful approach to identify the genetic determinants of a plethora of biological processes. We have previously validated the feasibility of this approach by identifying a point-mutated locus responsible for a specific phenotype, observed in an ethyl methanesulfonate (EMS)-mutagenized Caenorhabditis elegans strain. Here we describe the genome-wide mutational profile of 17 EMS-mutagenized genomes as assessed with a bioinformatic pipeline, called MAQGene. Surprisingly, we find that while outcrossing mutagenized strains does reduce the total number of mutations, a striking mutational load is still observed even in outcrossed strains. Such genetic complexity has to be taken into account when establishing a causative relationship between genotype and phenotype. Even though unintentional, the 17 sequenced strains described here provide a resource of allelic variants in almost 1000 genes, including 62 premature stop codons, which represent candidate knockout alleles that will be of further use for the C. elegans community to study gene function.