Genetic and haplotype diversity among wild-derived mouse inbred strains
Genetic and haplotype diversity among wild-derived mouse inbred strains
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DOI：
10.1101/gr.2519704
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发表时间：
2004-10-01
期刊：
影响因子：
7
通讯作者：
de Villena, FPM
中科院分区：
文献类型：
--
作者：
Ideraabdullah, FY;de la Casa-Esperón, E;de Villena, FPM
随着小鼠基因组序列的完成，有可能确定该物种遗传变异的数量，类型和组织。最近的报告提供了一个经典的实验室小鼠之间的遗传变异的结构的概述。另一方面，除了存在较高水平的多样性之外，对野生衍生菌株之间的遗传变异结构知之甚少。我们已经估计了序列多样性，由于20个近交系的小家鼠，选择一个明确的进化框架内的分子变异的解释之间的取代和插入/缺失。在这里，我们表明，这些菌株之间存在的序列多样性的水平是一个到两个数量级高于在人群中观察到的序列多样性的水平，只有一小部分的序列差异中发现的经典实验室菌株。我们的分析还表明，删除是显着更频繁的插入。我们估计在M. musculus可以在亚种内杂交中恢复。在变异位点的等位基因可分为164个菌株分布模式，数量超过了经典近交系的面板中报告和预测。菌株的数量、分散在基因组中的多个基因座的分析以及杂交菌株和经典菌株中基因组的镶嵌性质有助于观察到菌株分布模式的多样性。然而，系统发育分析表明，古老的多态性，跨物种和亚种分离菌株分布模式的产生中发挥了重要作用。
With the completion of the mouse genome sequence, it is possible to define the amount, type, and organization of the genetic variation in this species. Recent reports have provided an overview of the structure of genetic variation among classical laboratory mice. On the other hand, little is known about the structure of genetic variation among wild-derived strains with the exception of the presence of higher levels of diversity. We have estimated the sequence diversity due to substitutions and insertions/deletions among 20 inbred strains of Mus musculus, chosen to enable interpretation of the molecular variation within a clear evolutionary framework. Here, we show that the level of sequence diversity present among these strains is one to two orders of magnitude higher than the level of sequence diversity observed in the human population, and only a minor fraction of the sequence differences observed is found among classical laboratory strains. Our analyses also demonstrate that deletions are significantly more frequent than insertions. We estimate that 50% of the total variation identified in M. musculus may be recovered in intrasubspecific crosses. Alleles at variants positions can be classified into 164 strain distribution patterns, a number exceeding those reported and predicted in panels of classical inbred strains. The number of strains, the analysis of multiple loci scattered across the genome, and the mosaic nature of the genome in hybrid and classical strains contribute to the observed diversity of strain distribution patterns. However, phylogenetic analyses demonstrate that ancient polymorphisms that segregate across species and subspecies play a major role in the generation of strain distribution patterns.