Editing Pleiotropy (section)

{{short description|Influence of a single gene on multiple phenotypic traits}}
{{About|genetic pleiotropy|drug pleiotropy|Pleiotropy (drugs)}}
[[File:SimpleGenotypePhenotypeMap.jpg|thumb|Simple genotype–phenotype map that only shows additive pleiotropy effects. G1, G2, and G3 are different genes that contribute to phenotypic traits P1, P2, and P3.]]

'''Pleiotropy''' ({{etymology|grc|''{{wikt-lang|grc|πλείων}}'' ({{grc-transl|πλείων}})|more||''{{wikt-lang|grc|τρόπος}}'' ({{grc-transl|τρόπος}})|turn, way, manner, style}}) is a condition in which a single [[gene]] or genetic variant influences multiple [[phenotypic trait]]s. A gene that has such multiple effects is referred to as a ''pleiotropic gene''. [[Mutation]]s in pleiotropic genes can impact several traits simultaneously, often because the gene product is used in various [[cell (biology)|cells]] and affects different biological targets through shared signaling pathways. 

Pleiotropy can result from several distinct but potentially overlapping mechanisms, including [[gene]] pleiotropy, [[developmental biology|developmental]] pleiotropy, and selectional pleiotropy. Gene pleiotropy occurs when a gene product interacts with multiple [[protein]]s or catalyzes different reactions. Developmental pleiotropy refers to [[mutation]]s that produce several [[phenotype|phenotypic]] effects during development. Selectional pleiotropy occurs when a single phenotype influences evolutionary [[fitness (biology)|fitness]] in multiple ways (depending on factors such as age and sex).<ref name="Paaby 66–73">{{Cite journal|last1=Paaby|first1=Annalise B.|last2=Rockman|first2=Matthew V.|date=2016-11-15|title=The many faces of pleiotropy |journal=Trends in Genetics|volume=29 |issue=2|pages=66–73 |doi=10.1016/j.tig.2012.10.010 |pmc=3558540|pmid=23140989}}</ref>

There are also three main types of genetic pleiotropic effects when a variant or gene is associated with more than one trait: 

* ''Biological pleiotropy'', where a genetic variant directly affects multiple traits through biological pathways.
* ''Mediated pleiotropy'', where a variant influences one trait, which in turn causes changes in a second trait, and
* ''Spurious pleiotropy'', where statistical or methodological biases make it falsely appear as though a variant is associated with multiple traits.<ref>{{Cite journal |last1=Solovieff |first1=Nadia |last2=Cotsapas |first2=Chris |last3=Lee |first3=Phil H. |last4=Purcell |first4=Shaun M. |last5=Smoller |first5=Jordan W. |date=July 2013 |title=Pleiotropy in complex traits: challenges and strategies |journal=Nature Reviews Genetics |language=en |volume=14 |issue=7 |pages=483–495 |doi=10.1038/nrg3461 |issn=1471-0056 |pmc=4104202 |pmid=23752797}}</ref>

A well- known example of pleiotropy is [[phenylketonuria|phenylketonuria (PKU)]], a genetic disorder caused by a mutation in a single gene on chromosome 12 that encodes the enzyme [[phenylalanine hydroxylase]]. This mutation leads to the accumulation of the amino acid phenylalanine in the body, affecting multiple systems, such as the nervous and [[integumentary system]].<ref name="National Center for Biotechnology Information-1998">{{cite book |chapter=Phenylketonuria |title=Genes and Disease |date=1998 |publisher=National Center for Biotechnology Information |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK22253/ }}</ref>

Pleiotropic gene action can limit the rate of multivariate evolution when [[natural selection]], [[sexual selection]] or [[artificial selection]] on one trait favors one allele, while selection on other traits favors a different allele. Pleiotropic mutations can sometimes be deleterious, especially when they negatively affect essential traits. [[Genetic correlation]]s and responses to selection most often exemplify pleiotropy.

Pleiotropy is widespread in the genome, with many genes influencing biological traits and pathways. Understanding pleiotropy is crucial in genome- wide association studies ([[GWAS catalog|GWAS)]], where variants are often linked to multiple traits or diseases.