Genetic Network Complexity Shapes Background-Dependent Phenotypic Expression

Trends Genet. 2018 Aug;34(8):578-586. doi: 10.1016/j.tig.2018.05.006. Epub 2018 Jun 11.


The phenotypic consequences of a given mutation can vary across individuals. This so-called background effect is widely observed, from mutant fitness of loss-of-function variants in model organisms to variable disease penetrance and expressivity in humans; however, the underlying genetic basis often remains unclear. Taking insights gained from recent large-scale surveys of genetic interaction and suppression analyses in yeast, we propose that the genetic network context for a given mutation may shape its propensity of exhibiting background-dependent phenotypes. We argue that further efforts in systematically mapping the genetic interaction networks beyond yeast will provide not only key insights into the functional properties of genes, but also a better understanding of the background effects and the (un)predictability of traits in a broader context.

Keywords: background effect; conditional gene essentiality; genetic interaction; variable phenotypic expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Epistasis, Genetic
  • Evolution, Molecular
  • Gene Expression*
  • Gene Regulatory Networks*
  • Genetic Association Studies
  • Genetic Background*
  • Genetics, Population
  • Humans
  • Mutation
  • Phenotype*
  • Quantitative Trait Loci
  • Quantitative Trait, Heritable
  • Yeasts / genetics