Sequential elimination of major-effect contributors identifies additional quantitative trait loci conditioning high-temperature growth in yeast

Several quantitative trait loci (QTL) mapping strategies have successfully identified major-effect loci based on their strong association with the phenotype in segregating populations. Although mapping strategies have been designed to detect minor-effect loci, many of these strategies have had poor success rates, potentially due to the confounding effects of major loci and epistasis. Therefore, to avoid confounding effects of major loci, epistasis and sample size, we used a targeted backcross mapping strategy that genetically eliminated the effect of a previously identified major QTL underlying high-temperature growth (Htg) in yeast. This targeted backcross strategy facilitated the mapping of three novel QTL contributing to Htg of a clinically-derived yeast strain, one of which was linked to the previously identified, major-effect QTL. The dissection of this novel, linked QTL identified NCS2 as the causative gene, the interaction of which with the first, major-effect QTL was background-dependent, leading to a complex QTL architecture. This complex architecture suggests that a larger than predicted number of genes is likely to contribute to quantitative traits. Moreover, the targeted backcrossing approach, by sequentially eliminating the effects of contributing alleles from segregating populations overcomes the difficulties posed by genetic linkage and epistatic effects and facilitates identification of additional alleles with smaller contributions to complex traits.

Key Words: Epistasis, High temperature growth, Quantitative trait, Saccharomyces cerevisiae, clinical isolate

Online ISS 1091-6490
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