For over a century, inbred mice have been used in many areas of genetics research to gain insight into the genetic variation underlying traits of interest. The generalizability of any genetic research study in inbred mice is dependent upon all individual mice being genetically identical, which in turn is dependent on the breeding designs of companies that supply inbred mice to researchers. Here, we compare whole-genome sequences from individuals of four commonly used inbred strains that were procured from either the colony nucleus or from a production colony (which can be as many as ten generations removed from the nucleus) of a large commercial breeder, in order to investigate the extent and nature of genetic variation within and between individuals. We found that individuals within strains are not isogenic, and there are differences in the levels of genetic variation that are explained by differences in the genetic distance from the colony nucleus. In addition, we employ a novel approach to mutation rate estimation based on the observed genetic variation and the expected site frequency spectrum at equilibrium, given a fully inbred breeding design. We find that it provides a reasonable per nucleotide mutation rate estimate when mice come from the colony nucleus (~7.9 × 10 −9 in C3H/HeN), but substantially inflated estimates when mice come from production colonies.

中文翻译：

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近交实验室小鼠不是等基因的：近交系内的遗传变异用于推断每个核苷酸位点的突变率

一个多世纪以来，近交系小鼠已被用于遗传学研究的许多领域，以深入了解潜在性状的遗传变异。在近交系小鼠中进行的任何基因研究的普遍性取决于所有个体小鼠的基因相同，而这又取决于向研究人员提供近交系小鼠的公司的育种设计。在这里，我们比较了四种常用近交系个体的全基因组序列，这些菌株来自大型商业育种者的菌落核或生产菌落（从细胞核中去除多达十代），在为了调查个体内部和个体之间遗传变异的程度和性质。我们发现菌株中的个体不是等基因的，遗传变异水平的差异可以通过与菌落核的遗传距离的差异来解释。此外，在完全近交育种设计的情况下，我们采用了一种基于观察到的遗传变异和平衡时预期位点频谱的突变率估计新方法。我们发现，当小鼠来自菌落核（C3H/HeN 中约为 7.9 × 10 -9）时，它提供了合理的每个核苷酸突变率估计值，但当小鼠来自生产菌落时，估计值大大夸大了。给定一个完全自交育种设计。我们发现，当小鼠来自菌落核（C3H/HeN 中约为 7.9 × 10 -9）时，它提供了合理的每个核苷酸突变率估计值，但当小鼠来自生产菌落时，估计值大大夸大了。给定一个完全自交育种设计。我们发现，当小鼠来自菌落核（C3H/HeN 中约为 7.9 × 10 -9）时，它提供了合理的每个核苷酸突变率估计值，但当小鼠来自生产菌落时，估计值大大夸大了。