Study of an allelic series using transcriptomic phenotypes

Expression profiling holds great promise for genetics because of its ability to measure thousands of genes quantitatively. Although transcriptomes have recently been used to perform epistasis analyses for pathway reconstruction, there has not been a systematic effort to understand how expression profiles will vary among distinct mutants of the same gene. Here, we study an allelic series in C. elegans consisting of one wild type and two mutant alleles of mdt-12, a highly pleiotropic gene whose gene product is a subunit of Mediator complex, which is essential for transcriptional regulation in eukaryotes. We developed a false hit analysis to identify which populations of genes commonly differentially expressed with respect to the wild type are likely the result of statistical artifact. We concluded that expression perturbations caused by these alleles split into four distinct modules called phenotypic classes. To understand the dominance relationship between the two mutant alleles, we developed a dominance analysis for transcriptional data. Dominance analysis of these phenotypic classes support a model where mdt-12 has multiple functional units that function independently to target the Mediator complex to specific genetic loci. Overall design: 7 genotypes; 3 samples per genotype except for the trans-heterozygote, which has 4 replicates