Experimental evolution to probe gene networks underlying cognition in Drosophila
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1
Cold Spring Harbor Laboratory, United States
One of the great challenges to understanding genetic impact on human cognitive disorders is that clinical outcomes often are influenced by interactions among groups of genes. A good example is schizophrenia, where no clear genetic mechanism has emerged. In some individuals, complex disorders such as schizophrenia likely emerge from co-inheritance of multiple common gene variants each of which would have little clinical impact on their own. Despite its widespread relevance, mechanisms by which multi-gene interactions modulate phenotype are ill understood because almost all mechanistic studies of gene interaction are limited to pair-wise combinations. To investigate this question, we have developed and implemented a novel approach in Drosophila, using the biologically important and clinically relevant cAMP pathway as a model. Our approach uses the power of selective breeding to evolve combinations of gene variants capable of ameliorating the learning defect of a mutation in the rutabaga adenylyl cyclase gene. This method is novel in several ways. First, unlike a classical suppressor screen, our use of experimental evolution has allowed us to explore the impact of higher order combinations of gene interactions. Also, unlike a classical selective breeding experiment, we have constrained the genetic variability to a set of 23 identified and molecularly characterized loci with known involvement in memory. Our strategy models the multi-gene interactions that influence naturally occurring variation in complex phenotypes such as learning, but also makes it feasible to fully genotype the causative loci across multiple animals. This has given us unprecedented access to the underlying molecular genetic mechanisms.
Conference:
Computational and Systems Neuroscience 2010, Salt Lake City, UT, United States, 25 Feb - 2 Mar, 2010.
Presentation Type:
Oral Presentation
Topic:
Oral presentations
Citation:
Dubnau
J
(2010). Experimental evolution to probe gene networks underlying cognition in Drosophila.
Front. Neurosci.
Conference Abstract:
Computational and Systems Neuroscience 2010.
doi: 10.3389/conf.fnins.2010.03.00063
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Received:
19 Feb 2010;
Published Online:
19 Feb 2010.
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Correspondence:
Josh Dubnau, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States, joshua.dubnau@stonybrook.edu