16.18: Epistasis Analysis

Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The expression of a gene might depend on a gene product in the same biochemical pathway.

Epistatic analysis

The study of epistatic interactions allows researchers to determine the functional relationship between genes, the ordering of genes in a pathway, and how different alleles quantitatively impact phenotypes. Consider a biochemical reaction catalyzed by multiple proteins coded by different genes. The genes involved in such biochemical reactions can mask or inhibit other genes involved in the same biochemical pathway, a phenomenon called epistasis. Such genes are said to be in one epistasis group. By analyzing the epistatic relationship between different genes, scientists can construct an order-of-function map that shows the sequence of events and genes involved in a pathway. This process is called epistatic analysis. The alleles selected for the epistatic analysis must have distinct phenotypes.

As such, since the concept of epistasis was introduced, it has become increasingly clear that most biological systems involve many genetic elements that interact with one another in multiple and complex ways.

A contrary relationship between two genes is epistasis, where one gene masks or alters the expression of another. The influencing gene is said to be epistatic to the gene being masked.

For example, a gene that codes for tyrosinase-related protein 1, or TYRP1, determines the coat color of dogs —  black or brown.

Another gene, Tyr, codes for the enzyme tyrosinase, which is responsible for pigmentation in animals. A mutation in this gene can cause the absence of pigment, resulting in an albino dog which lacks any coloration.

The order in which these two genes are expressed can be determined by an epistasis test.

If a mutation in the Tyr gene produces an albino dog that still has the wild-type TYRP1 gene, it can be concluded that the Tyr gene masks the effect of the TYRP1 gene. This would mean that Tyr is epistatic to TYRP1.