Interdisciplinary Training

Charles Carey

"Correspondence Between Genotype, Phenotype and Gene Expression"

There is an imperfect correspondence between genotype and phenotype. Identical genomes share a common genetic susceptibility to expression of traits or disease, yet the penetrance of traits or disease may be confined to only some individuals. To model the correspondence between genotype, phenotypic penetrance and gene expression using Drosophila, we will examine the deformed eye trait (dfe), which is penetrant in only some individuals inheriting identical genotypes and raised in identical conditions. Penetrance, the probability that an individual with a given genotype manifests dfe, varies reliably from one genotype to the next, as it is exquisitely sensitive to genetic background. We have mapped >9 loci required for dfe penetrance by using quantitative trait locus mapping methods. In this proposal, we will test for a correspondence between gene expression and dfe penetrance. We will directly compare genetically identical flies that have and do not have dfe to establish the relationship between the dfe phenotype and gene expression. We will also establish the effect of penetrance on gene expression by comparing multiple genotypes having different degrees of penetrance. We will determine the relationship between genes identified by transcriptome analysis and genes identified by QTL and deletion mapping, and test select genes by transgenic and/or mutant analysis to directly assess and prove their effect on dfe penetrance and gene expression. Our proposal will result in an understanding of the relationship between dfe genotype, phenotypic penetrance and gene expression.