Friday, August 29, 2008

The Next Locus is Always Harder

Source: Brem, R.B., Storey, J.D., Whittle, J., and Kruglyak, L. Genetic interactions between polymorphisms that affect gene expression in yeast. 2005. Nature, 436(7051): 701-3

The authors took the transcript data for yeast and searched for interacting loci. They found that the best approach was to search for primary loci, then separate segregants based on allele inherited at that locus and search jointly for another locus. Using this approach, they found that not a large amount of transcripts had detectable interactions and those that did were isolated. One hotspot did appear for loci-pairs, the MAT-GPA relation, these genes are involved in mating type and pheromone response respectively. They used this hotspot to test their interaction theory, creating four engineered strains with the combination of alleles, but identical background, and comparing them to similar-genotyped segregants, finding that most of the phenotypes had parallel responses.

•Other notes:
-identified locus pairings for 225 transcripts
-65% had interaction based on model and FDR
•test on 547 transcripts with two independent loci showed only 13% interacting
-only 33% of secondary loci would have been picked up in a genome scan originally
-hypothesize that half of transcripts are controlled by multiple genetic interactions but that at least one partner has effects too low for mapping



Dual-linking transcripts are plotted in 2-D, with their primary linkage locus on the x-axis, and their secondary on the y-axis. Circles are proportional (in misleading width, NOT area) by the number of transcripts in each 2-D bin. The largest is the GPA-MAT region.

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