Mouse consomic strains: Exploiting genetic divergence between Mus m musculus and Mus m domesticus subspecies
Mouse consomic strains: Exploiting genetic divergence between Mus m musculus and Mus m domesticus subspecies
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DOI：
10.1101/gr.7160508
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发表时间：
2008-03-01
期刊：
影响因子：
7
通讯作者：
Forejt, Jiri
中科院分区：
文献类型：
--
作者：
Gregorova, Sona;Divina, Petr;Forejt, Jiri
染色体替换品系是近年来发现的一种新的小鼠遗传资源，其目的是对复杂性状基因座进行遗传分析。在这项研究中，我们报告了一组28小鼠亚种间CS的发展。在每个CS中，我们替换了C57 BL/6 J（86）近交系（主要是Mus m.与来自Mus m.亚种肌这两个祖先亚种在不到100万年前分化，积累了大量的遗传差异，构成了QTL分析的丰富遗传变异资源。总共，18个染色体、9个亚染色体和1个共质体菌株覆盖了所有19个常染色体、X和Y性染色体以及线粒体DNA。大多数CSs有显着较低的生殖适合度相比，祖株。CS同源染色体10和11，和C57 BL/6 J-Chr X男性，未能繁殖，并取代受影响较小的亚同源体携带的近端，中央或远端部分的相应染色体。对965个DNA标记的全基因组扫描显示B6遗传背景的纯度为99.87%。在B6.PWD-mt共质体株的线粒体DNA的蛋白质编码区中发现了33个非同义替换。一项先导表型实验项目揭示了B6.PWD同体基因中的大量变异。
Consomic (chromosome substitution) strains (CSs) represent the most recent addition to the mouse genetic resources aimed to geneticaly analyze complex trait loci (QTLs). In this study, we report the development of a set of 28 mouse intersubspecific CSs. In each CS, we replaced a single chromosome of the C57BL/6J (86) inbred strain (mostly Mus m. domesticus) with its homolog from the PWD/Ph inbred strain of the Mus m. musculus subspecies. These two progenitor subspecies diverged less than 1 million years ago and accumulated a large number of genetic differences that constitute a rich resource of genetic variation for QTL analyses. Altogether, the 18 consomic, nine subconsomic, and one conplastic strain covered all 19 autosomes, X and Y sex chromosomes, and mitochondrial DNA. Most CSs had significantly lower reproductive fitness compared with the progenitor strains. CSs homosomic for chromosomes 10 and 11, and the C57BL/6J-Chr X males, failed to reproduce and were substituted by less affected subconsomics carrying either a proximal, central, or distal part of the respective chromosome. A genome-wide scan of 965 DNA markers revealed 99.87% purity of the B6 genetic background. Thirty-three nonsynonymous substitutions were uncovered in the protein-coding regions of the mitochondrial DNA of the B6.PWD-mt conplastic strain. A pilot-phenotyping experiment project revealed a high number of variations among B6.PWD consomics.