epistasis
Shao H, Burrage LC, Sinasac DS, Hill AE, Ernest SR, O'Brien W, Courtland H-W, Jepsen KJ, Kirby A, Kulbokas EJ, Daly MJ, Broman KW, Lander ES & Nadeau JH 2008 Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis. PNAS 105:19910-19914.
- individual chromosome substitutions often conferred surprisingly large effects
- the sum of these individual effects often dramatically exceeded the difference between the parental strains
- strong, pervasive epistasis may reflect the presence of several phenotypically-buffered physiological states
- striking epistasis is rarely detected in humans and model organisms
- one possibility may be that the statistical power to detect pairwise epistasis is typically low both in segregating populations and in crosses with multiple segregating epistatic loci that can obscure pairwise effects
- another possibility may be that the genetic architecture varies substantially among traits
- a third possibility is that the study design strongly influences the picture of the genetic architecture obtained
- the presence of strong epistasis may reflect important features of the biological systems that control development and physiology
- but should not affect predictions about the effects of natural or artificial selection
- the underlying systems may have several stable regimes
- some genetic perturbations have small phenotypic effects that leave the system in one stable regime
- others may propel systems from one region of relative stability to another by crossing critical physiological thresholds
