Long and short range multi-locus QTL interactions in a complex trait of yeast

We analyse interactions of Quantitative Trait Loci (QTL) in heat selected yeast by comparing them to an unselected pool of random individuals. Here we re-examine data on individual F12 progeny selected for heat tolerance, which have been genotyped at 25 locations identified by sequencing a selected pool [Parts, L., Cubillos, F. A., Warringer, J., Jain, K., Salinas, F., Bumpstead, S. J., Molin, M., Zia, A., Simpson, J. T., Quail, M. A., Moses, A., Louis, E. J., Durbin, R., and Liti, G. (2011). Genome research, 21(7), 1131-1138]. 960 individuals were genotyped at these locations and multi-locus genotype frequencies were compared to 172 sequenced individuals from the original unselected pool (a control group). Various non-random associations were found across the genome, both within chromosomes and between chromosomes. Some of the non-random associations are likely due to retention of linkage disequilibrium in the F12 population, however many, including the inter-chromosomal interactions, must be due to genetic interactions in heat tolerance. One region of particular interest involves 3 linked loci on chromosome IV where the central variant responsible for heat tolerance is antagonistic, coming from the heat sensitive parent and the flanking ones are from the more heat tolerant parent. The 3-locus haplotypes in the selected individuals represent a highly biased sample of the population haplotypes with rare double recombinants in high frequency. These were missed in the original analysis and would never be seen without the multigenerational approach. We show that a statistical analysis of entropy and information gain in genotypes of a selected population can reveal further interactions than previously seen. Importantly this must be done in comparison to the unselected population's genotypes to account for inherent biases in the original population.