Epistasis plays an important role in the genetic architecture of common human diseases and can be viewed from two perspectives, biological and statistical, each derived from and leading to different assumptions and research strategies. Biological epistasis is the result of physical interactions among biomolecules within gene regulatory networks and biochemical pathways in an individual such tha...

Genome-wide association (GWA) studies have identified a number of loci underlying variation in human serum uric acid (SUA) levels with the SLC2A9 gene having the largest effect identified so far. Gene-gene interactions (epistasis) are largely unexplored in these GWA studies. We performed a full pair-wise genome scan in the Italian MICROS population (n = 1201) to characterise epistasis signals i...

Biological functions typically involve complex interacting molecular networks, with numerous feedback and regulation loops. How the properties of the system are affected when one, or several of its parts are modified is a question of fundamental interest, with numerous implications for the way we study and understand biological processes and treat diseases. This question can be rephrased in ter...

ENETIC load has been defined as the extent to which an equilibrium population is impaired because not all individuals are of optimum genotype. The concept, first discussed by HALDANE (1937), is the basis of theory developed by CROW (1958) and others for assessing the relative impact of various facets of the genetic system (especially mutation, segregation and inbreeding) on the average fitness ...

Meiotic recombination and the factors affecting its rate fate in nature have inspired many studies theoretical evolutionary biology. Classical models inferred that can be favored under a rather restricted parameter range. Thus, ubiquity of remains an open question. However, these assumed constant with equal across all individuals within population, whereas empirical evidence suggests may displa...

The role of gene interactions in the evolutionary process has long been controversial. Although some argue that they are not of importance, because most variation is additive, others claim that their effect in the long term can be substantial. Here, we focus on the long-term effects of genetic interactions under directional selection assuming no mutation or dominance, and that epistasis is symm...

BACKGROUND Epistasis has been historically used to describe the phenomenon that the effect of a given gene on a phenotype can be dependent on one or more other genes, and is an essential element for understanding the association between genetic and phenotypic variations. Quantifying epistasis of orders higher than two is very challenging due to both the computational complexity of enumerating a...

The genetic architecture of a phenotype consists of the genes, the interactions among them (epistasis), and the interactions among genes and environments (G · E) that affect the phenotype’s expression (Wade et al., 2001). For a phenotype with a ‘complex’ genetic architecture, epistasis and G · E play significant roles as opposed to a phenotype with a ‘simple’ architecture, in which interactions...

For different fitness mutational models, with epistasis introduced, we simulated the consequences of drift (D scenario) or mutation, selection, and drift (MSD scenario) in populations at the MSD balance subsequently subjected to bottlenecks of size N = 2, 10, 50 during 100 generations. No "conversion" of nonadditive into additive variance was observed, all components of the fitness genetic vari...

Parallel and convergent evolution have been remarkably common observations in molecular adaptation but primarily in the context of the same genotype adapting to the same conditions. These phenomena therefore tell us about the stochasticity and limitations of adaptation. The limited data on convergence and parallelism in the adaptation of different genotypes conflict as to the importance of such...