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Pleiotropy

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Related terms
Background
Methods
Research
Implications
Safety
Future research
Author information
Bibliography

Related Terms
  • Antagonistic pleiotropy, PCA, PCH, phenlketonuria, phenotype, PKU, pleiotrope, principal component analysis, principal component of heritability.

Background
  • Pleiotropy occurs when a single gene influences the expression of a gene in more than one way. A gene is the basic unit of heredity in a living organism. A single gene is made of a specific sequence of nitrogen molecules within a molecule of deoxyribonucleic acid (DNA). DNA makes up chromosomes that are passed on from parent to child.
  • Pleiotropy is when a mutation in a gene causes changes in two unrelated observable traits. For example, pleiotropy causes phenylketonuria (PKU), which is a disorder characterized by intellectual disabilities and reduced skin and hair pigmentation. Mutations in a pleiotropic gene may also result in changes in traits that seem unrelated. A mutation in a pleiotropic gene can have an effect on a variety of traits.
  • In antagonistic pleiotropy, the expressed gene produces some positive and some negative observable traits, resulting in multiple competing effects within the organism. As an example, during youth the gene coding for testosterone enables reproduction; however, later in life the production of testosterone is responsible for traits such as prostate cancer.
  • Furthermore, the environment can influence whether or not pleiotropy is antagonistic. This occurs, for example, when the genetic mutation within an organism favors the conditions of the environment it lives in, such as developing a mutation to use a certain type of energy from a particular food source. Pleiotropy would not be antagonistic if there are ample sources of that food available; however, it would be antagonistic if that food were scarce.
  • Pleiotropy is thought to be necessary for natural selection, the process by which more desirable inherited traits become more common in each generation of a population, while less desirable inherited traits become less common.

Methods
  • Principal component analysis (PCA): Principal component analysis (PCA) is a technique that uses algebra to simplify data in order to analyze and understand it. PCA is used to identify clusters of variables that may be controlled by a common gene or genes. This type of analysis allows for categorization of genes, while also allowing for ordering genes with complex characteristics into multiple categories. This approach has been conducted with C. elegans, where it was noted that about half the genes could be placed into more than one category; this allows for identification of previously undiscovered genes.
  • Principal component of heritability (PCH): Principal component of heritability (PCH) looks at each gene variable, also known as a single nucleotide polymorphism (SNP), to assess its relationship to each observable trait. PCH may make it possible to determine the association between a SNP and a trait.

Research
  • Because not much is understood about pleiotropy, current research is focused on identifying pleiotropic genes to determine whether multiple observable trait mutations occur as a result of this one genetic mutation, or if in fact, multiple trait defects are a result of multiple and separate genetic mutations. One classic pleiotropic mutation is a disease called phenylketonuria, or PKU, which is caused by one of many mutations on a single gene that is needed to produce a certain enzyme. This enzyme is not produced in people with PKU, so they cannot break down the amino acid phenylalanine. The buildup of phenylalanine may cause intellectual disabilities, reduced hair growth, and decreased skin coloration. Patients with PKU need to follow a strict diet with limited amounts of phenylalanine, which is primarily found in foods that are high in protein. This restrictive diet has been shown to effectively eliminate symptoms of PKU.

Implications
  • Various disease states and/or conditions may occur as a result of pleiotropy. In antagonistic pleiotropy, the expressed gene produces some positive and some negative observable traits, resulting in multiple competing effects within the organism. As an example, during youth, the gene coding for testosterone enables reproduction; however, later in life the production of testosterone is responsible for traits such as prostate cancer.
  • As another example, pleiotropy causes phenylketonuria (PKU), which is a disorder characterized by intellectual disabilities and reduced skin and hair pigmentation. Mutations in a pleiotropic gene may also result in changes in traits that seem unrelated. A mutation in a pleiotropic gene may affect a variety of traits.

Safety




Future research
  • As scientists learn more about pleiotropy and identify the ways in which it is related to complex diseases, they may be able to modify negative aspects of disease and tailor therapy to patients' individual needs. Future research on the expression and function of pleiotropic genes will provide a new target for identification of individuals prone to certain diseases and to develop common treatments that may be used to treat a variety of conditions that arise from pleiotropy.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Arya R, Lehman D, Hunt KJ, et al. Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study. BMC Genet. 2003; 31(4):S52.
  2. Bensen JT, Lange LA, Langefeld CD, et al. Exploring pleiotropy using principal components. BMC Genet. 2003;4(Suppl 1):S53.
  3. Genetics Home Reference. . Accessed March 27, 2008.
  4. Klei L, Luca D, Devlin B, et al. Pleiotropy and principal components of heritability combine to increase power for association analysis. Genet Epidemiol. 2008;32(1):9-19.
  5. Liu XQ, Hanley AJ, Paterson AD. Genetic analysis of common factors underlying cardiovascular disease-related traits. BMC Genet. 2003; 31(4): S56.
  6. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2008. Accessed March 27, 2008.
  7. Pavlicev M, Kenney-Hunt JP, Norgard EA, et al. Genetic variation in pleiotropy: differential epistasis as a source of variation in the allometric relationship between long bone lengths and body weight. Evolution Int J Org Evolution. 2008;62(1):199-213.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


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.

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