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Screening for Complex Genetic Interactions

Screening for Complex Genetic Interactions

In a report published online ahead of the January 15th print edition, Dr. David Amberg (SUNY Upstate Medical University) and colleagues have developed a large-scale reverse genetic screen to identify complex haploinsufficient interactions in S. cerevisiae. A complex haploinsufficiency (CHI) interaction is defined by heterozygous null/wildtype alleles in two different genes that combine to yield a more severe phenotypic defect. To illustrate the utility of this novel approach, the researchers culled through nearly 5000 strains of yeast to identify over 200 genes that interact with actin. This paper is one of the first example of a large-scale CHI screen, and it is expected that this kind of systemic analysis will be particularly useful in uncovering complex genetic interactions in other organisms, including the study of human genetic disorders. Dr. Amberg states that "We knew that actin was an important gene but we were still surprised at the large number of CHI interactions we uncovered. This test case suggests that CHI interactions in complex organisms have major influences on phenotype."

As published in the January 15th issue of G&D, Dr. Robert Tjian (HHMI, UC Berkeley) and colleagues reveal a novel mechanism of transcriptional/translational coupling in the fruit fly, Drosophila. The researchers found that the Drosophila insulin signaling pathway utilizes IRES-dependent (or cap-independent) translation to synthesize the insulin-like receptor protein when insulin is not readily available. The mechanism they uncovered effectively coordinates the organism's response nutrient availability and cell growth.

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