Complex quantitative traits cracked by the mouse inter-subspecific consomic strains

Mammalian quantitative traits that are observed at the whole-body level, such as body weight and length and blood biochemical parameters, are determined by the cooperative effects of multiple genetic and epigenetic factors as well as environmental factors. This complexity has hampered the genetic analysis of quantitative traits. To overcome this difficulty, we have established a full set of consomic mouse strains, also known as chromosome substitution strains, by replacing every chromosome of the classical inbred strain C57BL/6J with its counterpart from the Japanese wild-mouse-derived inbred strain MSM/Ms. The core components of the genomes of these two strains originated from different mouse subspecies. The inter-subspecific large-genome divergence and phenotypic differences between the two strains allowed the identification of genetic determinants for many quantitative traits by comprehensive phenotype screening. For some quantitative traits, the genetic determinants could be dissected into multiple chromosomes, thereby reflecting strain differences between C57BL/6J and MSM/Ms and their simple additive effects on the background of the consomic host strain. For other quantitative traits, the measured values of some consomic strains often far exceeded the range of the two parental strains, which suggests that nonadditive genetic interactions occur among multiple genes located on the substituted MSM/Ms chromosomes and the consomic host chromosomes. Thus, the inter-subspecific consomic strains are unique tools that can be used to identify both additive and nonadditive genetic effects on quantitative complex traits.