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Genetic interactions are the key to understanding complex traits
Date:1/22/2009

lled sporulation. Cohen acknowledges it's not a particularly fascinating trait, but it is one that can be measured easily and precisely.

"We don't have any particular fondness for sporulation," he says. "We are simply using it as a model to understand how multiple genes interact to influence variation in a biological process. Our hope is that a complex trait is put together in yeast in a similar way as it is in humans."

When it comes to sporulation, the yeast from the oak tree samples produce spores with 99 percent efficiency; the vineyard strains are far less efficient, at seven percent.

The scientists discovered that just four variants, or single nucleotide polymorphisms (SNPs), in three yeast genes account for nearly 90 percent of the genetic contribution to sporulation efficiency. By moving each of the four variants from one yeast strain to the other, they produced oak strains that sporulated like vineyard strains and vice versa.

"To put this into context, there are about 85,000 SNP differences between the two strains of yeast, and by moving just four of them, we effectively reversed the phenotype of the two strains," Cohen says.

The researchers also exchanged every combination of the four SNPs between the yeast strains to determine how the genetic variations interacted. Interestingly, any two or more of variants from the oak tree strain increased sporulation efficiency far more than would have been expected based on the individual contributions of each SNP.

"The variations interacted like crazy," Cohen says. "The combined effects of variants were always larger than the sum of their individual effects."

Understanding these interactions was critical for the scientists to accurately predict how a strain would behave based on the variations it carries in its genome. Only by accounting for the interactions between variants could they predict how particular variants combine to increase or decrease
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Contact: Caroline Arbanas
arbanasc@wustl.edu
314-286-0109
Washington University School of Medicine
Source:Eurekalert  

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