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Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells [Genetics]
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2020-11-10 , DOI: 10.1073/pnas.2018633117
Yang Sui 1, 2 , Lei Qi 1, 2 , Jian-Kun Wu 1 , Xue-Ping Wen 1 , Xing-Xing Tang 1 , Zhong-Jun Ma 1 , Xue-Chang Wu 3 , Ke Zhang 3 , Robert J. Kokoska 4 , Dao-Qiong Zheng 1 , Thomas D. Petes 2
Affiliation  

Genomic alterations including single-base mutations, deletions and duplications, translocations, mitotic recombination events, and chromosome aneuploidy generate genetic diversity. We examined the rates of all of these genetic changes in a diploid strain of Saccharomyces cerevisiae by whole-genome sequencing of many independent isolates (n = 93) subcloned about 100 times in unstressed growth conditions. The most common alterations were point mutations and small (<100 bp) insertion/deletions (n = 1,337) and mitotic recombination events (n = 1,215). The diploid cells of most eukaryotes are heterozygous for many single-nucleotide polymorphisms (SNPs). During mitotic cell divisions, recombination can produce derivatives of these cells that have become homozygous for the polymorphisms, termed loss-of-heterozygosity (LOH) events. LOH events can change the phenotype of the cells and contribute to tumor formation in humans. We observed two types of LOH events: interstitial events (conversions) resulting in a short LOH tract (usually less than 15 kb) and terminal events (mostly cross-overs) in which the LOH tract extends to the end of the chromosome. These two types of LOH events had different distributions, suggesting that they may have initiated by different mechanisms. Based on our results, we present a method of calculating the probability of an LOH event for individual SNPs located throughout the genome. We also identified several hotspots for chromosomal rearrangements (large deletions and duplications). Our results provide insights into the relative importance of different types of genetic alterations produced during vegetative growth.



中文翻译:

二倍体酵母细胞中自发遗传改变的全基因组图谱[遗传]

基因组改变包括单碱基突变,缺失和重复,易位,有丝分裂重组事件和染色体非整倍性产生了遗传多样性。我们通过在无应力生长条件下亚克隆约100倍的许多独立分离株(n = 93)的全基因组测序,研究了酿酒酵母二倍体菌株中所有这些遗传变化的速率。最常见的变化是点突变和小的(<100 bp)插入/缺失(n = 1,337)和有丝分裂重组事件(n= 1,215)。大多数真核生物的二倍体细胞对于许多单核苷酸多态性(SNP)是杂合的。在有丝分裂细胞分裂期间,重组可以产生这些细胞的衍生物,这些衍生物对于多态性(称为杂合丢失(LOH)事件)成为纯合子。LOH事件可以改变细胞的表型,并有助于人类肿瘤的形成。我们观察到两种类型的LOH事件:间隙事件(转换)导致较短的LOH区域(通常小于15 kb)和终端事件(主要是交叉),其中LOH区域延伸至染色体末端。这两种类型的LOH事件具有不同的分布,表明它们可能是由不同的机制引发的。根据我们的结果,我们提出了一种计算整个基因组中单个SNP发生LOH事件的概率的方法。我们还确定了几个染色体重排的热点(大的缺失和重复)。我们的结果提供了对营养生长过程中产生的不同类型遗传变异相对重要性的见解。

更新日期:2020-11-12
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