Can We Predict the Magnitude and Direction of Epistasis from Individual Allelic Effects?

Abstract

Linking allelic variants to variation for complex traits has been a major focus in modern genetics. However, the ability to assess and predict how genetic factors influence complex traits (including human disease) requires an understanding of the specific genes that influence a trait, but also a broader understanding of the genetic architecture of complex traits. Epistatic interactions are crucial when mapping genotypic to phenotypic effects, as mutations in two (or more) genes can produce a phenotype that differs substantially from the expectation of the sum of individual effects. Epistatic interactions are both common and vary considerably in magnitude. Yet little current research focuses on identifying and predicting when mutations will have epistatic interactions and the extent of such effects. I examined the extent of epistatic interactions as a function of individual allelic effects (magnitudes) and wild-type genetic background using the Drosophila melanogaster wing as a model system. The aim of this research is to demonstrate whether individual mutational effects are predictive of the magnitude and direction of epistatic interactions. My results indicate 1) relationships between the average mutant effect and the resulting epistasis and 2) the genetic background can have a strong influence on epistasis.