Mouse inter-subspecific consomic strains for genetic dissection of quantitative complex traits

被引:73
作者
Takada, Toyoyuki [1 ,2 ]
Mita, Akihiko [2 ,3 ]
Maeno, Akiteru [2 ]
Sakai, Takahiro [3 ]
Shitara, Hiroshi [3 ]
Kikkawa, Yoshiaki [3 ]
Moriwaki, Kazuo [4 ]
Yonekawa, Hiromichi [3 ]
Shiroishi, Toshihiko [1 ,2 ]
机构
[1] Res Org Informat & Syst, Transdisciplinary Res Intergrat Ctr, Minato Ku, Tokyo 1050001, Japan
[2] Natl Inst Genet, Mammalian Genet Lab, Shizuoka 4118540, Japan
[3] Tokyo Metropolitan Inst Med Sci, Dept Lab Anim Sci, Bunkyo Ku, Tokyo 1138613, Japan
[4] RIKEN, Tsukuba Inst, BioResource Ctr, Tsukuba, Ibaraki 3050006, Japan
关键词
D O I
10.1101/gr.7175308
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:500 / 508
页数:9
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