When considering the relative utility of HBCGM, it is reasonable to ask whether 3 distinct phenotypic states will be a rare or common occurrence when a trait is evaluated across a large panel of inbred strains. Of direct relevance, mouse laboratory strains are reproductively isolated populations, which were derived from at least 3 subspecies (Mus musculus domesticus, M. m. musculus, and M. m. casteneus) that diverged ~1 million years ago (reviewed in [21]). Analysis of murine SNPs indicated that 4 distinct subspecies contributed to the genetic variation in the inbred strains, the vast majority of genetic variation is derived from the founding subspecies, and 40% of murine genes contain 3 or more different haplotypic patterns [22]. Since both mouse genealogy and murine SNP analysis indicates that many genomic regions could have 3 or more haplotypic patterns, the presence of 3 different phenotypic states may be a common occurrence when phenotypes are analyzed across a larger number of strains. Since over 450 inbred mouse strains have been described [23], a substantial number of inbred strains are available for phenotypic analyses.
