Fazlollahi et al. have developed a computational approach to determine genetic variants that affect the functional interactions of gene regulatory networks. Using this algorithm, the team were able to map so-called connectivity quantitative trait loci (cQTLs). These cQTLs are natural genetic variants that influence the regulatory interactions of specific transcription factors and their target genes (for example, a polymorphism that occurs in the coding or promoter sequence of a required cofactor). Application of the algorithm to yeast genotype and gene expression data revealed a non-synonymous polymorphism in the DIG2 gene that acts as a cQTL for the transcription factor Ste12p. That is, the variant modulates the strength of the Ste12p-mediated transcriptional response to mating pheromone, as validated experimentally, through its alteration of the encoded amino acid sequence.