Symmetric Epistasis Estimation (SEE) and its application to dissecting interaction map of Plasmodium falciparum

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Molecular BioSystems (Impact Factor: 3.21). 03/2012; 8(5):1544-52. DOI: 10.1039/c2mb05333k
Source: PubMed


It is being increasingly recognized that many important phenotypic traits, including various diseases, are governed by a combination of weak genetic effects and their interactions. While the detection of epistatic interactions that involve a non-additive effect of two loci on a quantitative trait is particularly challenging, this interaction type is fundamental for the understanding of genome organization and gene regulation. However, current methods that detect epistatic interactions typically rely on the existence of a strong primary effect, considerably limiting the sensitivity of the search. To fill this gap, we developed a new method, SEE (Symmetric Epistasis Estimation), allowing the genome-wide detection of epistatic interactions without the need for a strong primary effect. We applied our approach to progeny crosses of the human malaria parasite P. falciparum and S. cerevisiae. We found an abundance of epistatic interactions in the parasite and a much smaller number of such interactions in yeast. The genome of P. falciparum also harboured several epistatic interaction hotspots that putatively play a role in drug resistance mechanisms. The abundance of observed epistatic interactions might suggest a mechanism of compensation for the extremely limited repertoire of transcription factors. Interestingly, epistatic interaction hotspots were associated with elevated levels of linkage disequilibrium, an observation that suggests selection pressure acting on P. falciparum, potentially reflecting host-pathogen interactions or drug-induced selection.

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    • "The paucity of uncovered epistasis depends not only on the method and the definition of epistasis, but also on the dataset. For example, in our study (Huang et al., 2012) we found that the same method, allowing us to identify abundant presence of epistatic interactions in the population of progenies in plasmodium reported much smaller number of interactions in yeast. Such a difference might relate to the fact that the parental strains of P. falciparum are under strong evolutionary pressure to adapt independently to the host environment. "
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    ABSTRACT: The determination of expression quantitative trait loci (eQTL) epistasis - a form of functional interaction between genetic loci that affect gene expression - is an important step toward the thorough understanding of gene regulation. Since gene expression has emerged as an "intermediate" molecular phenotype eQTL epistasis might help to explain the relationship between genotype and higher level organismal phenotypes such as diseases. A characteristic feature of eQTL analysis is the big number of tests required to identify associations between gene expression and genetic loci variability. This problem is aggravated, when epistatic effects between eQTLs are analyzed. In this review, we discuss recent algorithmic approaches for the detection of eQTL epistasis and highlight lessons that can be learned from current methods.
    Full-text · Article · May 2013 · Frontiers in Genetics