Epistasis Blog

From the Computational Genetics Laboratory at Dartmouth Medical School (www.epistasis.org)

Wednesday, August 15, 2012

Epistasis in Yeast

Leonid Kruglyak has put his latest paper on arXiv for comment. This is a well-written paper that explores additive and non-additive genetic effects for a variety of traits in yeast. The discussion of the results is comprehensive and informative. I would love to see this work extended to higher-order gene-gene interactions and gene-environment interactions. We need more work like this as we try to understand the complexity of genetic architecture. It is interesting to note that there has been some discussion about putting papers on arXiv for public viewing prior to publication. See this Nature News piece for an introduction to the topic.

Finding the sources of missing heritability in a yeast cross

Joshua S. Bloom, Ian M. Ehrenreich, Wesley Loo, Thúy-Lan Võ Lite, Leonid Kruglyak

Abstract

For many traits, including susceptibility to common diseases in humans, causal loci uncovered by genetic mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this "missing heritability" have been proposed. Here we use a large cross between two yeast strains to accurately estimate different sources of heritable variation for 46 quantitative traits and to detect underlying loci with high statistical power. We find that the detected loci explain nearly the entire additive contribution to heritable variation for the traits studied. We also show that the contribution to heritability of gene-gene interactions varies among traits, from near zero to 50%. Detected two-locus interactions explain only a minority of this contribution. These results substantially advance our understanding of the missing heritability problem and have important implications for future studies of complex and quantitative traits.

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