epistatic interaction
Pronunciation: ep-ih-STAT-ik
The phenomenon where the effect of one genetic variant is modified or masked by the presence of variants in other genes within the same pathway.
Full Definition
Epistatic interaction describes how genetic variants in different genes can interact to modify each other's phenotypic effects, either enhancing, suppressing, or completely masking the individual variant impacts. In cancer genomics, epistasis is particularly important for understanding synthetic lethality relationships, where mutations in two genes individually may be tolerable but together are lethal to the cell. Examples include BRCA1/2 deficiency creating sensitivity to PARP inhibitors, or p53 loss modifying the effects of other oncogenic mutations. Recognition of epistatic relationships is crucial for interpreting multi-gene panel results and predicting therapeutic responses. These interactions can complicate variant classification and require consideration of the broader genomic context.
Usage
Usage note: Emphasize functional interaction rather than statistical association.
In Context
- "The epistatic interaction between BRCA2 and PALB2 mutations complicated risk assessment." — Genetic counseling report
- "Synthetic lethal epistasis was observed between DNA repair pathway components." — Functional genomics study