There seems to be endless combinations of gene variants that can occur from just four nucleotide letters. Some of these variants are harmless, but some can also change proteins with a damaging effect. Scientists are asking: which are which? Computational methods are a popular choice for determining disease-causing mutations, but scientists from the University of Toronto suggest a natural and more effective way to pick out the harmful variants: testing gene variants in baker’s yeast.
Lead researcher Fritz Roth, PhD, foresees his research laying the foundation for a resource for clinicians, a series of “look-up tables” to improve the success of each patient diagnosis.
“Many clinicians would not accept evidence about human variants based on how they perform in baker's yeast,” Roth said. “Our paper highlights the important and direct role that model organisms can play in interpreting individual human genomes.”
The new study, published in the journal Genome Research
, depicts a method using strains of yeast to “interpret people’s genomes” because the “basic architecture” of the same yeast strain used as a leavening agent in baking bread and in brewing beer is similar enough to human cells.
In order to test gene variants in yeast strains, Roth and his team knocked out yeast genes to see if the human counterpart gene could successfully replace this missing component. His prediction was that if the normal gene could help the yeast return to normal function but a mutated variant of the gene could not do the same, then the mutation must be damaging.
Yeast cultures grow quickly, and desired genes are easy to manipulate for testing. Roth and his team tested 22 genes and 179 variants relating to autism, mental retardation, and heart disease. Over half of the 179 variants were found to cause some sort of disease, majorly outperforming traditional computational methods’ abilities to sort the disease-causing variants from the harmless variants. The yeast method discovered 62 percent of damaging gene variants, while the smartest computer could only pinpoint 23 percent.
With a resource like the one dreamed up by Roth, personalized medicine for people with mutations of concern is possible, going forward with treatment for people with disease-causing variants and giving piece of mind to people with harmless mutations.
Source: University of Toronto