I determine limits to the equilibrium relationship among epistasis, recombination and disequilibrium in two-locus, two-allele models using linear programming techniques. I show that when allele frequencies are one-half at each locus, the symmetric model is the fitness pattern that generates the most disequilibrium for the smallest level of epistasis. When allele frequencies deviate from one-hal...

Epistasis is a key concept in the theory of adaptation. Indicators of epistasis are of interest for large systems where systematic fitness measurements may not be possible. Some recent approaches depend on information theory. We show that considering shared entropy for pairs of loci can be misleading. The reason is that shared entropy does not imply epistasis for the pair. This observation hold...

The goal of this study was to identify single-locus and epistasis effects of SNP markers on anti-cyclic citrullinated peptide (anti-CCP) that is associated with rheumatoid arthritis, using the North American Rheumatoid Arthritis Consortium data. A square root transformation of the phenotypic values of anti-CCP with sex, smoking status, and a selected subset of 20 single-nucleotide polymorphism ...

Epistasis helps to explain how multiple single-nucleotide polymorphisms (SNPs) interact to cause disease. A variety of tools have been developed to detect epistasis. In this article, we explore the strengths and weaknesses of an information theory approach for detecting epistasis and compare it to the logistic regression approach through simulations. We consider several scenarios to simulate th...

Epistasis is an important feature of the genetic architecture of quantitative traits, but the dynamics of epistatic interactions in natural populations and the relationship between epistasis and pleiotropy remain poorly understood. Here, we studied the effects of epistatic modifiers that segregate in a wild-derived Drosophila melanogaster population on the mutational effects of P-element insert...

Viral capsids are structurally constrained by interactions amongst the amino acids of the constituting proteins. Therefore, epistasis is expected to evolve amongst sites engaged in physical interactions, and to influence their substitution rates. In order to study the distribution of structural epistasis, we modeled in silico the capsid of 18 species of the φχ174 family, including the wild type...

Deleterious mutations can have a strong influence on the outcome of evolution. The nature of this influence depends on how mutations combine together to affect fitness. "Negative epistasis" occurs when a new deleterious mutation causes the greatest loss in fitness in a genome that already contains many deleterious mutations. Negative epistasis is a key ingredient for some of the leading hypothe...

Sex dimorphism in recombination is widespread on both sex chromosomes and autosomes. Various hypotheses have been proposed to explain these dimorphisms. Yet no theoretical model has been explored to determine how heterochiasmy--the autosomal dimorphism--could evolve. The model presented here shows three circumstances in which heterochiasmy is likely to evolve: (i) a male-female difference in ha...

BACKGROUND Epistasis, i.e., the interaction of alleles at different loci, is thought to play a central role in the formation and progression of complex diseases. The complexity of disease expression should arise from a complex network of epistatic interactions involving multiple genes. METHODOLOGY We develop a general model for testing high-order epistatic interactions for a complex disease i...

Genetic interactions in fitness are studied by using modifier theory. The effects on fitness of two linked genes are perturbed by alleles at a third linked locus that controls the extent of epistasis in fitness between the first two. This epistasis is determined by a symmetric interaction matrix, and it is shown that a modifier allele that increases epistasis will invade when the linkage betwee...