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.
References
Fazlollahi, M. et al. Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets. Proc. Natl Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1517140113 (2016)
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Koch, L. New tool to map genetic modifiers of transcription factor–gene target connections. Nat Rev Genet 17, 255 (2016). https://doi.org/10.1038/nrg.2016.43
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DOI: https://doi.org/10.1038/nrg.2016.43