Epistatic Pleiotropy and the Genetic Architecture of Skull Trait Complexes in Mice.

A new paper by Wolf et al. in Genetics presents evidence that genetic integration in the skull is achieved by a complex combination of pleiotropic effects.

Wolf J, Leamy LJ, Routman E, Cheverud JM. Epistatic Pleiotropy and the Genetic Architecture of Covariation Within Early- and Late-Developing Skull Trait Complexes in Mice. Genetics. 2005 Jul 14; [Epub ahead of print] [PubMed]

Abstract:

The role of epistasis as a source of trait variation is well established, but its role as a source of covariation among traits (i.e., as a source of "epistatic pleiotropy") is rarely considered. In this study we examine the relative importance of epistatic pleiotropy in producing covariation within early- and late-developing skull trait complexes in a population of mice derived from an intercross of the Large and Small inbred strains. Significant epistasis was found for several pair-wise combinations of the 21 quantitative trait loci (QTL) affecting early-developing traits, and among the 20 QTL affecting late-developing traits. The majority of the epistatic effects were restricted to single traits but epistatic pleiotropy still contributed significantly to covariances. Because of their proportionally larger effects on variances than on covariances, epistatic effects tended to reduce within-group correlations of the early-developing (but not late-developing) traits and reduce their overall degree of integration. The expected contributions of single-locus and two-locus epistatic pleiotropic QTL effects to the genetic covariance between traits were analyzed using a two-locus population genetic model. The model demonstrates that, in order for single-locus or epistatic pleiotropy to contribute to trait covariances in the study population, both traits must show the same pattern of genetic effects. In general, covariance patterns produced by single-locus and epistatic pleiotropy predicted by the model agreed well with actual values calculated from the QTL analysis. Nearly all single-locus and epistatic pleiotropic effects contributed positive components to covariances between traits, suggesting that genetic integration in the skull is achieved by a complex combination of pleiotropic effects.