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Nat Rev Genet. 2014 Jan;15(1):22-33. doi: 10.1038/nrg3627. Epub 2013 Dec 3.

Epistasis and quantitative traits: using model organisms to study gene-gene interactions.

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Department of Biological Sciences, Campus Box 7614, North Carolina State University, Raleigh, North Carolina 27695-7614, USA.


The role of epistasis in the genetic architecture of quantitative traits is controversial, despite the biological plausibility that nonlinear molecular interactions underpin the genotype-phenotype map. This controversy arises because most genetic variation for quantitative traits is additive. However, additive variance is consistent with pervasive epistasis. In this Review, I discuss experimental designs to detect the contribution of epistasis to quantitative trait phenotypes in model organisms. These studies indicate that epistasis is common, and that additivity can be an emergent property of underlying genetic interaction networks. Epistasis causes hidden quantitative genetic variation in natural populations and could be responsible for the small additive effects, missing heritability and the lack of replication that are typically observed for human complex traits.

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