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Epistasis is the interaction between genes. Epistasis takes place when the effects of one gene are modified by one or several other genes, which are sometimes called modifier genes. The gene whose phenotype is expressed is said to be epistatic, while the phenotype altered or suppressed is said to be hypostatic. Epistasis should be distinguished from Dominance, which is an interaction between alleles at the same gene locus.
In general, the fitness increment of any one allele depends in a complicated way on many other alleles; but, because of the way that the science of population genetics was developed, evolutionary scientists tend to think of epistasis as the exception to the rule. In the first models of natural selection devised in the early 20th century, each gene was considered to make its own characteristic contribution to fitness, against an average background of other genes. Some introductory college courses still teach population genetics this way.
Epistasis and genetic interaction refer to different aspects of the same phenomenon. The term epistasis is widely used in population genetics and refers especially to the statistical properties of the phenomenon, and does not necessarily imply biochemical interaction between gene products.
Examples of tightly linked genes having epistatic effects on fitness are found in supergenes and the human major histocompatibility complex genes. The effect can occur directly at the genomic level, where one gene could code for a protein preventing transcription of the other gene. Alternatively, the effect can occur at the phenotypic level. For example, the gene causing albinism would hide the gene controlling color of a person's hair. In another example, a gene coding for a widow's peak would be hidden by a gene causing baldness. Fitness epistasis (where the affected trait is fitness) is one cause of linkage disequilibrium.
Studying genetic interactions can reveal gene function, the nature of the mutations, functional redundancy, and protein interactions. Because protein complexes are responsible for most biological functions, genetic interactions are a powerful tool.

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Epistasis, the interaction between genes, is a topic of current interest in molecular and quantitative genetics. A large amount of research has been devoted to the detection and investigation of epistatic interactions. However, there has been much confusion in the literature over definitions and interpretations of epistasis. We note that the degree to which statistical tests of epistasis can elucidate underlying biological interactions may be more limited than previously assumed. Epistasis, defined generally as the interaction between different genes, has become a hot topic in complex disease genetics in recent years. For complex traits such as diabetes, asthma, hypertension and multiple sclerosis, the search for susceptibility loci has, to date, been less successful than for simple Mendelian disorders. This is probably due to complicating factors such as an increased number of contributing loci and susceptibility alleles, incomplete penetrance, and contributing environmental effects. The presence of epistasis is a particular cause for concern, since, if the effect of one locus is altered or masked by effects at another locus, power to detect the first locus is likely to be reduced and elucidation of the joint effects at the two loci will be hindered by their interaction. If more than two loci are involved, the situation is likely to be further complicated by the possibility of complex multiway interactions among some or all of the contributing loci.