Abstract
Experimental analysis of background dependenteffects of genetic interactions can be designed usingstrains generated by introgression of small geneticregions containing identical genotypes at loci in question into different inbred strains. We usea novel multilocus paradigm, denoted conditionalintergenic functional association (CIFA), to simulatethis procedure, with the trade-off of power forconvenience that is affordable when sufficiently strongeffects are present. We analyze nine enzyme loci atthree chromosomes in groups of D. melanogasterwith different developmental rates that showed similarallelic frequencies at individual loci. Resultsobtained suggest the presence of adaptive interactionbetween particular alleles at two loci when geneticvariation at seven background loci is eliminated.Biochemical considerations show that, in the resultingdevelopmental context, strong interaction between thesegenes may emerge from shifted control of the pentosephosphate pathway, with cascading effects on theglycolysis, TCA cycle, and biosynthetic pathways: one genemay assume control of the irreversible rate-limitingstep in the pentose phosphate pathway, whereas the othergene may assume control of the NADP+ levelthat regulates the same rate-limiting step as anelectron acceptor. The newly developing functionalgenomics research and the absence of inbreeding makeCIFA directly applicable to complex human traits inlarge samples.
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Kovac, I., Marinkovic, D. Analysis of Background-Dependent Genetic Interactions Without Inbred Strains. Biochem Genet 37, 23–40 (1999). https://doi.org/10.1023/A:1018761916601
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DOI: https://doi.org/10.1023/A:1018761916601