Last update: Thursday, 13-Mar-2014 12:31:00 EDT | ||||||
The dictionary of genetic effectsSupport: National Science Foundation (DEB 0950002), National Institutes of Health (5R01GM094424) |
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We have manipulated genetic expression in Drosophila to produce a first-order approximation to the genotype-phenotype map of wing shape, and we have dubbed this effort the dictionary of genetic effects. Starting from the principles (1) that both genotypic and phenotypic variation are complex and multidimensional, making their mapping a very cumbersome endeavor, and (2) that the mapping of macro-effects (e.g., gene knockouts) informs little about the causes of natural variation, we have implemented a system that allows us to introduce gradual, controlled knockdowns in gene expression, and measure their phenotypic effects as functions of the magnitude of the knockdowns. To date, we have phenotyped wing shape effects associated to misexpression of over 150 genes.
The critical contribution of the Dictionary goes beyond showing which-genes-have-what-effects; our dictionary is producing a catalog of wing shape traits with known causal origin. Unlike traditional measurements (e.g., length, area, or shape measurements), which are rarely chosen based on their biological meaning, dictionary traits comprise the phenotypic targets of changes in gene expression, and in principle contain the full (or measurable) set of pleiotropic effects of this change.
At present, we are exploring individual and collective variational properties of dictionary vectors, including their evolvability, modularity, and pleiotropy. We are also using dictionary vectors as traits in a GWAS, as selection gradients in artificial selection experiments, and as input parameters in a developmental model. We are interested in exploring the uses of these vectors in ecology, biogeography, ecophysiology, and similar applications. We are also quantifying phenotypic responses to gene expression perturbations as non-linear multivariate functions, focusing on two general aspects of non-linear behavior. First, we are cataloging the distinct pattern of non-linearity associated to each gene, e.g., threshold-limited, asymptotic, diminishing returns. This pattern, which we refer to as the phenotype of the gene in itself can be interpreted as a trait of the underlying regulatory system. Second, we are combining all of these functions in a common phenotype space centered on wild phenotypes (dubbed the spaghetti bowl, illustrated below), whose structure we are beginning to explore at multiple scales to search for causal links between genetic interactions and phenotypic covariation.
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Present and Past Projects | |||||
Márquez, E.J.; Moscarella, R.A.; Aponte, D.; Mio, W.; Houle, D. 2013. A Dictionary of Genetic Effects as a Unified Representation of the Genotype-Phenotype Map. 54th Annual Drosophila Research Conference, Washington, DC. [ ABSTRACT ]
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© 2003-2014 Eladio J. Márquez |