A paternally imprinted QTL for mature body mass on mouse Chromosome 8

Body mass (BM) is a classic polygenic trait that has been extensively investigated to determine the underlying genetic architecture. Many previous studies looking at the genetic basis of variation in BM in murine animal models by quantitative trait loci (QTL) mapping have used crosses between two inbred lines. As a consequence it has not been possible to explore imprinting effects which have been shown to play an important role in the genetic basis of early growth with persistent effects throughout the growth curve. Here we use partially inbred mouse lines to identify QTL for mature BM by applying both Mendelian and Imprinting models. The analysis of an F₂ population (n ≈ 500) identified a number of QTL at 14, 16, and 18 weeks explaining in total 31.5%, 34.4%, and 30.5% of total phenotypic variation, respectively. On Chromosome 8 a QTL of large effect (14% of the total phenotypic variance at 14 weeks) was found to be explained by paternal imprinting. Although Chromosome 8 has not been previously associated with imprinting effects, features of candidate genes within the QTL confidence interval (CpG islands and direct clustered repeats) support the hypothesis that Insulin receptor substrate 2 may be associated with imprinting, but as yet is unidentified as being so.