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The Gene-Environment Enigma

http://www.medicalnewstoday.com/articles/210289.php

Personalized medicine centers on being able to predict the risk of disease or

response to a drug based on a person's genetic makeup. But a study by scientists

at Washington University School of Medicine in St. Louis suggests that, for most

common diseases, genes alone only tell part of the story.

That's because the environment interacts with DNA in ways that are difficult to

predict, even in simple organisms like single-celled yeast, their research

shows.

" The effects of a person's genes - and, therefore, their risk of disease - are

greatly influenced by their environment, " says senior author Barak Cohen, PhD, a

geneticist at Washington University School of Medicine. " So, if personalized

medicine is going to work, we need to find a way to measure a human's

environment. "

The research is available online in PLoS Genetics.

To understand gene-environment interactions at the most basic level - at the

individual DNA letters that make up the genetic code - the researchers turned to

a model organism, the yeast Saccharomyces cerevisiae, culled from North American

oak trees and vineyards, where it grows naturally. They asked whether growing

the yeast in different environments would influence the rate at which the yeast

produce spores, a form of sexual reproduction.

This complex trait is heavily influenced by genetics, Cohen's earlier research

has shown. In a study published in 2009 in Science, he determined that just four

DNA variants, called single nucleotide polymorphisms (SNPs), account for 90

percent of the efficiency with which yeast produce spores.

In that study, the researchers noted that yeast from oak trees produced spores

with 99 percent efficiency; the vineyard strains were far less efficient, at 7

percent. Then, they put each combination of the four SNPs in both the oak and

vineyard strains, to determine how the genetic variants interacted with one

another.

The researchers showed that the four variants " interacted like crazy such that

the combined effects of any four variants were always larger than the sum of

their individual effects, " Cohen says.

By developing a statistical model to account for the genetic interactions, they

could genotype any combination of the four SNPs in either strain of yeast and

predict with a high level of confidence their effect on sporulation.

But in that study, the yeast were grown in the same environment - glucose.

In the current study, the scientists grew the two yeast strains with all 16

combinations of four SNPs in different simple sugars: glucose, fructose,

sucrose, maltose, raffinose, grape juice, galactose and a combination of

sucrose, glucose and fructose.

" These were all mono- or di-saccharides, so the environments are not radically

different from one another, " Cohen explains. " It's not like we heated up the

yeast or froze them, added acids or put them in a centrifuge. We simply changed

the carbon source and measured the effects of those four SNPs in the different

environments. "

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