Mouse inter-subspecific consomic strains for genetic dissection of quantitative complex traits
Mouse inter-subspecific consomic strains for genetic dissection of quantitative complex traits
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DOI：
10.1101/gr.7175308
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发表时间：
2008-03-01
期刊：
影响因子：
7
通讯作者：
Shiroishi, Toshihiko
中科院分区：
文献类型：
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作者：
Takada, Toyoyuki;Mita, Akihiko;Shiroishi, Toshihiko
同染色体菌株，也被称为染色体替代菌株，是分配控制数量复杂性状的多基因到特定染色体的有力工具。在这里，我们报道了一套完整的小鼠经济菌株的产生，其中常见的实验室菌株C57BL/6J （B6）的每条染色体都被来自日本野生小鼠小家鼠（Mus musculus molossinus）的近交系MSM/Ms的对应染色体所取代。MSM/Ms的基因组序列与136的基因组序列不同，136的基因组主要来源于西欧野生小鼠家鼠（Mus musculus domesticus）。MSM/Ms表现出与B6显著不同的数量复合性状。我们系统地确定了这些亚特异性间经济菌株的表型，重点关注与繁殖、生长和能量代谢相关的复杂性状。我们成功地检测到200多个具有统计学意义的qtl，影响26个性状。此外，经济菌株的表型分析表明，数量复杂性状的测量值往往远远超过B6宿主和MSM/Ms供体菌株之间的范围；这可能是由于等位基因的分离或来自两个小鼠亚种的多个基因之间的非加性相互作用（即上位性）。总之，结果表明，亚种间经济菌株将非常有助于鉴定数量复杂性状的潜在遗传成分。
Consomic strains, also known as chromosome substitution strains, are powerful tools for assigning polygenes that control quantitative complex traits to specific chromosomes. Here, we report generation of a full set of mouse consomic strains, in which each chromosome of the common laboratory strain C57BL/6J (B6) is replaced by its counterpart from the inbred strain MSM/Ms, which is derived from Japanese wild mouse, Mus musculus molossinus. The genome sequence of MSM/Ms is divergent from that of 136, whose genome is predominantly derived from Western European wild mouse, Mus musculus domesticus. MSM/Ms exhibits a number of quantitative complex traits markedly different from those of B6. We systematically determined phenotypes of these inter-subspecific consomic strains, focusing on complex traits related to reproduction, growth, and energy metabolism. We successfully detected more than 200 statistically significant QTLs affecting 26 traits. Furthermore, phenotyping of the consomic strains revealed that the measured values for quantitative complex traits often far exceed the range between B6 host and MSM/Ms donor strains; this may result from segregation of alleles or nonadditive interactions among multiple genes derived from the two mouse subspecies (that is, epistasis). Taken together, the results suggest that the inter-subspecific consomic strains will be very useful for identification of latent genetic components underlying quantitative complex traits.