Yeast cells expressing proteins.Image courtesy of UCLAUsing different strains of a yeast called Saccharomyces cerevisiae, a single-celled fungus, they studied hundreds of thousands of genetically different yeast cells — orders of magnitude more than previously examined — making their approach statistically powerful and significantly more revealing about how genetic differences influence gene expression.
They also directly studied protein levels, an approach that differed from earlier work, which focused on levels of messenger RNA (mRNA), the intermediate molecules that cells use to read genes and translate them into proteins. While mRNAs are easier to measure than proteins, their levels don’t always correspond to protein levels.
The two-and-a-half-year study found that the protein expression of a typical gene is influenced by many more genetic variants than previously thought and that the effects of genetic differences on mRNA levels corresponded much more closely to the effects on protein expression than seen earlier. Additionally, there is a complex web of variants that affects a large fraction of the proteins in cells.
IMPACT:
The work could shed light on the study of disease risk in humans, as genetic variants that influence disease often act by affecting the expression of genes. Clinical applications may eventually flow from a better understanding of the process of genetic variants and protein expression.
AUTHORS:
Authors include Frank W. Albert, a UCLA postdoctoral researcher, and Leonid Kruglyak, a UCLA professor of human genetics and biological chemistry and a Howard Hughes Medical Institute investigator.
FUNDING:
The study was funded by the National Institutes of Health (RO1 GM102308), the Howard Hughes Medical Institute, the McDonnell Foundation, the National Science Foundation and the German Research Foundation (DFG).
JOURNAL:
The research
appears in the Jan. 8 early online edition of the journal Nature. A copy of the full study is also available. Using different strains of a yeast called Saccharomyces cerevisiae, a single-celled fungus, they studied hundreds of thousands of genetically different yeast cells — orders of magnitude more than previously examined — making their approach statistically powerful and significantly more revealing about how genetic differences influence gene expression.
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