Epistasis refers to any interaction between different genes. Genes are found inside the cells of all organisms. An individual's genes are present in a large molecule called DNA (deoxyribonucleic acid), which looks like a twisted ladder. This unique shape is called a double helix. The sides of the double helix are made of alternating sugar and phosphate molecules. The "rungs" of the "ladder" are made of smaller molecules that contain nitrogen. These molecules include adenine, thymine, cytosine, and guanine.
All genes are made up of different combinations of these four molecules, which are arranged in different lengths. The sequence of these molecules provides the "code," or instructions, for each of the genes involved in the development, growth, and function of all the cells in the body. When genes are expressed, the information they contain is translated into a physical trait such as eye color.
Epistasis can occur when a mutation, or defect, in one gene (or in multiple genes) covers up the expression of a mutation in a different gene. This can also occur when a mutation in one gene enhances the mutation in another gene. The phenotype, or expression, is therefore different than if the two gene mutations were expressed independently.
The gene that is expressed is said to be epistatic. The gene that is not expressed is said to be hypostatic. For example, a mutant or defective gene that causes complete baldness would be epistatic because it would prevent the expression of the gene that determines hair color.
Epistasis refers to the interaction between different genes, not variations of the same gene. This distinguishes epistasis from the concept of gene dominance, in which one variant (or allele) of a gene covers up the expression of another variant of the same gene.
The concept of epistasis is used in population genetics, in which the observation and study of genetic changes are observed in relation to evolutionary theories. Scientists have used mathematical models to try to predict the interaction between different genes, but this is proving to be difficult because the interactions can be very complex.
General: Epistasis can be classified in several different ways:
Genetic suppression: In some instances of epistasis, the expression of one gene prevents another gene from being expressed. For example, one gene may provide instructions for a protein that silences another gene or renders it inactive. Genetic suppression would therefore also cause the product of the second gene to be inactive. For example, if gene A is expressed, it shuts down the expression of gene B.
Genetic enhancement: Epistasis can also occur when one gene enhances the expression of another gene. For example, the product of one gene may be a protein that activates the expression of another gene. In other words, if gene A is expressed, it activates the expression of gene B. The epistatic interaction can also occur at the protein level, where the protein product of gene A enhances the activity of gene B's products.
Genetic modifiers: Genetic modifiers may affect several variables regarding the expression of a gene, including where and when certain traits occur. For example, mutations in the CFTR gene cause cystic fibrosis. Researchers found that a mutation, or defect, in another gene, TGF?1, changes the way CFTR is expressed, and thereby reduces the severity of the disease.
General: The study of genetic interactions is extremely important in that it can reveal the function of genes, how genetic variations affect human health and disease, whether genes with similar functions exist, and how proteins interact. This type of research may help researchers learn more about many types of medical conditions, such as Alzheimer's disease, cystic fibrosis, and obesity.
A major barrier to studies of epistasis in humans is getting enough study subjects to allow for significant results. When small samples are used, study results are more likely to be due to chance. When larger study samples are used, researchers may be more confident that their results were not due to chance.
Alzheimer's disease: Scientists believe that epistasis is an important feature of complex conditions such as Alzheimer's disease. Research in this area may help them understand factors involved in the development and treatment of the disease.
Cystic fibrosis: The severity of lung disease in cystic fibrosis has been studied extensively. Scientists have found that the degree of lung disease may be due to a variation in the CFTR gene or the TGF?1 gene.
Obesity: Scientists have identified 11 different genes that cause human obesity and many more genes that cause obesity in laboratory experiments in mice. It is believed that more genetic contributors to obesity exist but are currently undiscovered due to potential masking, or epistasis, by other genetic factors.
Information gained through the study of epistasis may eventually allow scientists to understand the complex nature of many diseases. As researchers learn more about diseases, it may help develop new treatments, diagnostic tests, and prevention strategies. In the future, this understanding may also allow for the development of medical care that is tailored to individual needs such as disease susceptibilities.
At the present time, it is very difficult to study epistasis in humans. A major barrier to studies of epistasis in humans is getting enough study subjects to allow for significant results. When small samples are used, study results are more likely to be due to chance. When larger study samples are used, researchers are more able to rule out the effect of chance.
Using animal and cell culture (or "in vitro") models, scientists can more easily manipulate genes for the purposes of studying specific gene interactions. Although epistatic interactions may be easier to examine in these models, it is often not clear if findings from animal or in vitro studies may be extended to humans.
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The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.