Epistasis

Epistasis occurs when the phenotype produced by one gene depends on which alleles are present at a different gene. The gene doing the masking is called epistatic, and the gene whose effect is hidden is called hypostatic. This differs from dominance, which describes the relationship between two alleles of the same gene.

Epistasis often arises when genes act at successive steps of one biochemical pathway. In mice, one gene is needed to make any pigment at all, and a second gene decides whether the coat is agouti or a solid color. A mouse with two nonfunctional copies of the pigment gene is albino, whatever it carries at the coat-pattern gene. Labrador retrievers show a similar pattern: one gene sets black or chocolate pigment, but two recessive copies of another gene keep pigment out of the hair, giving a yellow coat.

Because of epistasis, a cross between parents heterozygous for both genes no longer gives Mendel's 9:3:3:1 ratio. Recessive epistasis in mice gives 9:3:4, dominant epistasis in summer squash gives 12:3:1, and other gene pairs give 9:7 or 15:1. In human genetics, the term also covers interactions between variants that make the risk of complex diseases harder to predict.