View source for Allele

{{Short description|One of alternative forms of the same gene}}
{{Use dmy dates|date=July 2020}}

An '''allele'''{{refn|{{IPAc-en|UK|ˈ|æ|l|iː|l|,_|ə|ˈ|l|iː|l}}; modern formation from Greek ἄλλος ''állos'', "other"}} (or '''allelomorph''') is a variant of the sequence of [[nucleotide]]s at a particular location, or [[Locus (genetics)|locus]], on a [[DNA]] molecule.<ref>{{ cite book | last = Graur | first = D | title = Molecular and Genome Evolution | publisher = Sinauer Associates, Inc. | place = Sunderland MA (USA) | date = 2016 }}</ref>

Alleles can differ at a single position through [[Single-nucleotide polymorphism|single nucleotide polymorphisms]] (SNP),<ref>{{Cite journal|last1=Smigielski|first1=Elizabeth M.|last2=Sirotkin|first2=Karl|last3=Ward|first3=Minghong|last4=Sherry|first4=Stephen T.|date=2000-01-01|title=dbSNP: a database of single nucleotide polymorphisms|journal=Nucleic Acids Research|volume=28|issue=1|pages=352–355|issn=0305-1048|pmid=10592272|pmc=102496|doi=10.1093/nar/28.1.352}}</ref> but they can also have insertions and deletions of up to several thousand [[base pair]]s.<ref>{{Cite book|last1=Elston|first1=Robert|last2=Satagopan|first2=Jaya|last3=Sun|first3=Shuying|date=2012|chapter=Genetic Terminology|series=Methods in Molecular Biology|volume=850|pages=1–9|doi=10.1007/978-1-61779-555-8_1|issn=1064-3745|pmc=4450815|pmid=22307690|title=Statistical Human Genetics|isbn=978-1-61779-554-1}}</ref>

Most alleles observed result in little or no change in the function of the [[gene]] product it codes for. However, sometimes different alleles can result in different observable [[phenotypic trait]]s, such as different [[pigmentation]]. A notable example of this is [[Gregor Mendel]]'s discovery that the white and purple flower colors in [[pea]] plants were the result of a single gene with two alleles.

Nearly all [[multicellular organism]]s have two sets of [[chromosome]]s at some point in their [[biological life cycle]]; that is, they are [[diploid]]. For a given locus, if the two chromosomes contain the same allele, they, and the organism, are [[homozygous]] with respect to that allele. If the alleles are different, they, and the organism, are [[heterozygous]] with respect to those alleles.

Popular definitions of 'allele' typically refer only to different alleles within genes. For example, the [[ABO blood group system|ABO blood grouping]] is controlled by the [[ABO (gene)|ABO gene]], which has six common alleles (variants). In [[population genetics]], nearly every living human's [[phenotype]] for the ABO gene is some combination of just these six alleles.<ref>{{cite journal | vauthors = Seltsam A, Hallensleben M, Kollmann A, Blasczyk R | title = The nature of diversity and diversification at the ABO locus | journal = Blood | volume = 102 | issue = 8 | pages = 3035–42 | date = October 2003 | pmid = 12829588 | doi = 10.1182/blood-2003-03-0955 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ogasawara K, Bannai M, Saitou N, Yabe R, Nakata K, Takenaka M, Fujisawa K, Uchikawa M, Ishikawa Y, Juji T, Tokunaga K | title = Extensive polymorphism of ABO blood group gene: three major lineages of the alleles for the common ABO phenotypes | journal = Human Genetics | volume = 97 | issue = 6 | pages = 777–83 | date = June 1996 | pmid = 8641696 | doi = 10.1007/BF02346189 | s2cid = 12076999 }}</ref>

==Etymology==
The word "allele" is a short form of "allelomorph" ("other form", a word coined by British geneticists [[William Bateson]] and [[Edith Rebecca Saunders]]) in the 1900s,<ref>{{cite web | last = Craft | first = Jude | title = Genes and genetics: the language of scientific discovery | work = Genes and genetics | publisher = [[Oxford English Dictionary]] | date = 2013 | url = http://public.oed.com/aspects-of-english/shapers-of-english/genes-and-genetics-the-language-of-scientific-discovery/ | access-date = 2016-01-14 | archive-date = 29 January 2018 | archive-url = https://web.archive.org/web/20180129140501/http://public.oed.com/aspects-of-english/shapers-of-english/genes-and-genetics-the-language-of-scientific-discovery/ | url-status = live }}</ref><ref>Bateson, W. and Saunders, E. R. (1902) "The facts of heredity in the light of Mendel’s discovery." Reports to the Evolution Committee of the Royal Society, '''I.''' pp. 125–160</ref> which was used in the early days of [[genetics]] to describe variant forms of a [[gene]] detected in different [[phenotypes]] and identified to cause the differences between them. It derives from the [[Greek language|Greek]] prefix ἀλληλο-, ''allelo-'', meaning "mutual", "reciprocal", or "each other", which itself is related to the Greek adjective ἄλλος, ''allos'' (cognate with [[Latin]] ''alius''), meaning "other".

==Alleles that lead to dominant or recessive phenotypes==
{{main|Dominance (genetics)}}
In many cases, genotypic interactions between the two alleles at a locus can be described as [[Dominance (genetics)|dominant]] or [[recessive]], according to which of the two homozygous phenotypes the [[heterozygote]] most resembles. Where the heterozygote is indistinguishable from one of the homozygotes, the allele expressed is the one that leads to the "dominant" phenotype,<ref name="Essential genetics: A genomics perspective"/><ref name="pmid 28696921">{{cite journal|date=September 2017|title=ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy|journal=G3|volume=7|issue=9|pages=2931–2943|doi=10.1534/g3.117.044024|pmid=28696921|doi-access=free |last1=Monga |first1=Isha |last2=Qureshi |first2=Abid |last3=Thakur |first3=Nishant |last4=Gupta |first4=Amit Kumar |last5=Kumar |first5=Manoj |pmc=5592921 }}</ref> and the other allele is said to be "recessive". The degree and pattern of dominance varies among loci. This type of interaction was first formally-described by [[Gregor Mendel]]. However, many traits defy this simple categorization and the phenotypes are modelled by [[co-dominance]] and [[Quantitative trait locus|polygenic inheritance]].<ref>{{Cite web|url=https://www.genome.gov/genetics-glossary/Allele|title=Allele|website=Genome.gov|access-date=3 July 2021|archive-date=28 June 2021|archive-url=https://web.archive.org/web/20210628215931/https://www.genome.gov/genetics-glossary/Allele|url-status=live}}</ref>

The term "[[wild type]]" allele is sometimes used to describe an allele that is thought to contribute to the typical phenotypic character as seen in "wild" populations of organisms, such as fruit flies (''[[Drosophila melanogaster]]''). Such a "wild type" allele was historically regarded as leading to a dominant (overpowering – always expressed), common, and normal phenotype, in contrast to "[[mutant]]" alleles that lead to recessive, rare, and frequently deleterious phenotypes. It was formerly thought that most individuals were homozygous for the "wild type" allele at most gene loci, and that any alternative "mutant" allele was found in homozygous form in a small minority of "affected" individuals, often as [[genetic diseases]], and more frequently in heterozygous form in "[[Genetic carrier|carriers]]" for the mutant allele. It is now appreciated that most or all gene loci are highly polymorphic, with multiple alleles, whose frequencies vary from population to population, and that a great deal of genetic variation is hidden in the form of alleles that do not produce obvious phenotypic differences. Wild type alleles are often denoted by a superscript plus sign (''i.e.'', ''p{{sup|+}}'' for an allele ''p'').<ref>{{cite book|title = Genetics A Conceptual Approach|edition = 7|author = B. A. Pierce|publisher = Macmillan|date = 2020|isbn = 978-1-319-21680-1|page = 60}}</ref>

==Multiple alleles==
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| footer            = [[Eye color]] is an inherited trait influenced by [[Polygene|more than one gene]], including ''[[OCA2]]'' and ''[[HERC2]]''. The interaction of multiple genes—and the variation in these genes ("alleles") between individuals—help to determine a person's eye color [[phenotype]]. Eye color is influenced by [[pigment]]ation of the [[Iris (anatomy)|iris]] and the frequency-dependence of the light [[scattering]] by the [[Turbidity|turbid]] medium within the [[Stroma of iris|stroma]] of the iris.
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| image1            = Blue eye 2.jpg
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| image4            = Human eye with limbal ring, anterior view.jpg
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[[File:ABO blood type.svg|thumb|upright=1.45|In the [[ABO blood group system]], a person with Type A blood displays A-antigens and may have a genotype I<sup>A</sup>I<sup>A</sup> or I<sup>A</sup>i. A person with Type B blood displays B-antigens and may have the genotype I<sup>B</sup>I<sup>B</sup> or I<sup>B</sup>i. A person with Type AB blood displays both A- and B-antigens and has the genotype I<sup>A</sup>I<sup>B</sup> and a person with Type O blood, displaying neither antigen, has the genotype ii.]]

A population or [[species]] of organisms typically includes multiple alleles at each locus among various individuals. Allelic variation at a locus is measurable as the number of alleles ([[Genetic polymorphism|polymorphism]]) present, or the proportion of heterozygotes in the population. A [[null allele]] is a gene variant that lacks the gene's normal function because it either is not expressed, or the expressed protein is inactive.

For example, at the gene locus for the [[ABO]] [[blood type]] [[carbohydrate]] [[antigen]]s in humans,<ref name="OnlineMendelianInheritanceinMan"/> classical genetics recognizes three alleles, I<sup>A</sup>, I<sup>B</sup>, and i, which determine compatibility of [[blood transfusion]]s. Any individual has one of six possible [[genotype]]s (I<sup>A</sup>I<sup>A</sup>, I<sup>A</sup>i, I<sup>B</sup>I<sup>B</sup>, I<sup>B</sup>i, I<sup>A</sup>I<sup>B</sup>, and ii) which produce one of four possible [[phenotype]]s: "Type A" (produced by I<sup>A</sup>I<sup>A</sup> homozygous and I<sup>A</sup>i heterozygous genotypes), "Type B" (produced by I<sup>B</sup>I<sup>B</sup> homozygous and I<sup>B</sup>i heterozygous genotypes), "Type AB" produced by I<sup>A</sup>I<sup>B</sup> heterozygous genotype, and "Type O" produced by ii homozygous genotype. (It is now known that each of the A, B, and O alleles is actually a class of multiple alleles with different DNA sequences that produce proteins with identical properties: more than 70 alleles are known at the ABO locus.<ref name="Sequence variation at the human ABO locus"/> Hence an individual with "Type A" blood may be an AO heterozygote, an AA homozygote, or an AA heterozygote with two different "A" alleles.)

==Genotype frequencies==
{{main|Allele frequency}}
The frequency of alleles in a diploid population can be used to predict the frequencies of the corresponding genotypes (see [[Hardy–Weinberg principle]]). For a simple model, with two alleles;

: <math>p + q=1 \, </math>

: <math>p^2 + 2pq + q^2=1 \,</math>

where ''p'' is the frequency of one allele and ''q'' is the frequency of the alternative allele, which necessarily sum to unity. Then, ''p''<sup>2</sup> is the fraction of the population homozygous for the first allele, 2''pq'' is the fraction of heterozygotes, and ''q''<sup>2</sup> is the fraction homozygous for the alternative allele. If the first allele is dominant to the second then the fraction of the population that will show the dominant phenotype is ''p''<sup>2</sup> + 2''pq'', and the fraction with the recessive phenotype is ''q''<sup>2</sup>.

With three alleles:

: <math>p + q + r = 1 \, </math> and

: <math>p^2 + q^2 + r^2 + 2pq + 2pr + 2qr = 1. \,</math>

In the case of multiple alleles at a diploid locus, the number of possible genotypes (G) with a number of alleles (a) is given by the expression:

: <math>G= \frac{a(a+1)}{2}. </math>

==Allelic dominance in genetic disorders==
A number of [[genetic disorders]] are caused when an individual inherits two recessive alleles for a single-gene trait. Recessive genetic disorders include [[albinism]], [[cystic fibrosis]], [[galactosemia]], [[phenylketonuria]] (PKU), and [[Tay–Sachs disease]]. Other disorders are also due to recessive alleles, but because the gene locus is located on the X chromosome, so that males have only one copy (that is, they are [[hemizygosity|hemizygous]]), they are more frequent in males than in females. Examples include [[Congenital red–green color blindness|red–green color blindness]] and [[fragile X syndrome]].

Other disorders, such as [[Huntington's disease]], occur when an individual inherits only one dominant allele.

==Epialleles==
While [[heredity|heritable traits]] are typically studied in terms of genetic alleles, [[epigenetic]] marks such as [[DNA methylation]] can be inherited at specific genomic regions in certain species, a process termed [[transgenerational epigenetic inheritance]]. The term ''epiallele'' is used to distinguish these heritable marks from traditional alleles, which are defined by [[nucleotide sequence]].<ref>{{cite journal|last1=Daxinger|first1=Lucia|last2=Whitelaw|first2=Emma|title=Understanding transgenerational epigenetic inheritance via the gametes in mammals|journal=Nature Reviews Genetics|date=31 January 2012|volume=13|issue=3|pages=153–62|doi=10.1038/nrg3188|pmid=22290458|s2cid=8654616}}</ref> A specific class of epiallele, the [[metastable epiallele]]s, has been discovered in mice and in humans which is characterized by stochastic (probabilistic) establishment of epigenetic state that can be mitotically inherited.<ref>{{cite journal|last1=Rakyan|first1=Vardhman K|last2=Blewitt|first2=Marnie E|last3=Druker|first3=Riki|last4=Preis|first4=Jost I|last5=Whitelaw|first5=Emma|title=Metastable epialleles in mammals|journal=Trends in Genetics|date=July 2002|volume=18|issue=7|pages=348–351|doi=10.1016/S0168-9525(02)02709-9|pmid=12127774}}</ref><ref>{{cite journal|last1=Waterland|first1=RA|last2=Dolinoy|first2=DC|last3=Lin|first3=JR|last4=Smith|first4=CA|last5=Shi|first5=X|last6=Tahiliani|first6=KG|title=Maternal methyl supplements increase offspring DNA methylation at Axin Fused.|journal=Genesis|date=September 2006|volume=44|issue=9|pages=401–6|pmid=16868943|doi=10.1002/dvg.20230|s2cid=36938621}}</ref>

==Idiomorph==
The term "idiomorph", from Greek 'morphos' (form) and 'idio' (singular, unique), was introduced in 1990 in place of "allele" to denote sequences at the same locus in different strains that have no sequence similarity and probably do not share a common phylogenetic relationship. It is used mainly in the genetic research of [[mycology]].<ref>{{Cite journal |doi=10.1093/genetics/132.1.125 |doi-access=free |pmc=1205111 |pmid=1398049|title=Isolation of Neurospora crassa a mating type mutants by repeat induced point (RIP) mutation |year=1992 |last1=Glass |first1=N. L. |last2=Lee |first2=L. |journal=Genetics |volume=132 |pages=125–133 }}</ref><ref>{{Cite journal |doi=10.1002/bies.950120202|title=Mating type and mating strategies in ''Neurospora'' |year=1990 |last1=Metzenberg |first1=Robert L. |last2=Glass |first2=N. Louise |journal=BioEssays |volume=12 |issue=2 |pages=53–59 |pmid=2140508 |s2cid=10818930 }}</ref>

==See also==
{{Portal|Evolutionary biology}}
{{Columns-list|colwidth=22em|
* [[Allelotype]]
* [[Allozyme]]
* [[Evolution]]
* [[Genealogical DNA test]]
* [[Allele frequency]]
* [[Haploinsufficiency]]
* [[Meiosis]]
* [[Mendelian error]]
* [[Mendelian inheritance]]
* [[Mitosis]]
* [[Penetrance]]
* [[Polymorphism (biology)|Polymorphism]]
* [[Punnett square]]
* [[Single-nucleotide polymorphism]]
}}

==References and notes==
{{Reflist|refs=<ref name="OnlineMendelianInheritanceinMan">{{cite web|url=https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=110300 |title=ABO Glycosyltransferase; ABO |author1=Victor A. McKusick |author2=Cassandra L. Kniffin |author3=Paul J. Converse |author4=Ada Hamosh |date=10 November 2009 |work=Online Mendelian Inheritance in Man |publisher=National Library of Medicine |access-date=24 March 2010 |archive-url=https://web.archive.org/web/20080924220935/http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=110300 |archive-date=24 September 2008 |url-status=live}}</ref><ref name="Essential genetics: A genomics perspective">{{cite book |title=Essential genetics: A genomics perspective |edition=4th |last=Hartl |first=Daniel L. |author2=Elizabeth W. Jones |year=2005 |publisher=Jones & Bartlett Publishers |isbn=978-0-7637-3527-2 |page=600 }}<!--|access-date=5 October 2009--></ref><ref name="Sequence variation at the human ABO locus">{{cite journal |author=Yip SP |title=Sequence variation at the human ABO locus |journal=Annals of Human Genetics |volume=66 |issue=1 |pages=1–27 |date=January 2002 |pmid=12014997 |doi=10.1017/S0003480001008995|doi-access=free }}</ref>
}}

==External links==
{{Wiktionary|allele}}
* [http://alfred.med.yale.edu/alfred/index.asp ALFRED: The ALlele FREquency Database]

{{Genetics}}
{{Authority control}}
[[Category:Classical genetics]]
[[Category:Genetic genealogy]]