Editing Eye color (section)

==Genetic determination==
Eye color is an inherited trait determined by multiple [[gene]]s.<ref name="Sturm">{{cite journal |vauthors=Sturm RA, Frudakis TN|title=Eye colour: portals into pigmentation genes and ancestry |journal=Trends Genet. |volume=20 |issue=8 |pages=327–32 |year=2004 |pmid=15262401 |doi=10.1016/j.tig.2004.06.010 |url=http://www.biosci.ohio-state.edu/~pfuerst/courses/eeobmg640/reading1eyecolor.pdf |archive-url=https://web.archive.org/web/20060909190624/http://www.biosci.ohio-state.edu/~pfuerst/courses/eeobmg640/reading1eyecolor.pdf |archive-date=9 September 2006 }}</ref><ref name="Grant">{{cite journal|vauthors=Grant MD, Lauderdale DS|title=Cohort effects in a genetically determined trait: eye colour among US whites |journal=Ann. Hum. Biol. |volume=29 |issue=6 |pages=657–66 |year=2002 |pmid=12573082 |doi=10.1080/03014460210157394 |s2cid=25364754 }}</ref> These genes are sought by studying small changes in the genes themselves and in neighboring genes, called [[single-nucleotide polymorphism]]s or SNPs. The total number of genes that contribute to eye color is unknown, but there are a few likely candidates. A study in [[Rotterdam]] (2009) found that it was possible to predict eye color with more than 90% accuracy for brown and blue using just six SNPs.<ref>[https://www.newscientist.com/article/mg20126992.100-dna-test-for-eye-colour-could-help-fight-crime.html "DNA test for eye colour could help fight crime"], ''[[New Scientist]]'' 14 March 2009.</ref><ref>{{cite journal |last1=Liu |first1=Fan |last2=Van Duijn |first2=Kate |last3=Vingerling |first3=Johannes R. |last4=Hofman |first4=Albert |last5=Uitterlinden |first5=André G. |last6=Janssens |first6=A. Cecile J.W. |author-link6=A. Cecile J.W. Janssens |last7=Kayser |first7=Manfred |year=2009 |title=Eye color and the prediction of complex phenotypes from genotypes |journal=[[Current Biology]] |volume=19 |issue=5 |pages=R192–R193 |doi=10.1016/j.cub.2009.01.027 |pmid=19278628 |doi-access=free|bibcode=2009CBio...19.R192L }}</ref>

In humans, eye color is a highly sexually dimorphic trait.<ref name="Martinez-Cadenas Peña-Chilet Ibarrola-Villava Ribas 2013 pp. 453–460">{{cite journal | last1=Martinez-Cadenas | first1=Conrado | last2=Peña-Chilet | first2=Maria | last3=Ibarrola-Villava | first3=Maider | last4=Ribas | first4=Gloria | title=Gender is a major factor explaining discrepancies in eye colour prediction based on HERC2/OCA2 genotype and the IrisPlex model | journal=Forensic Science International: Genetics | publisher=Elsevier BV | volume=7 | issue=4 | year=2013 | issn=1872-4973 | doi=10.1016/j.fsigen.2013.03.007 | pages=453–460| pmid=23601698 | hdl=10234/86709 | hdl-access=free }} "This effect is what may explain the fact that there seem to be comparatively higher frequencies of blue-eyed males than blue-eyed females in populations of European origin such as Iceland [10], Holland [10], Australia [18] or Poland [17], as well as in this study (see Fig. 2)."</ref> Several studies have shown that men are more likely to have blue eyes than women, while women are more likely to have darker eye colors (green and brown eyes) than men.<ref name="Martinez-Cadenas Peña-Chilet Ibarrola-Villava Ribas 2013 pp. 453–460" /><ref name="t967">{{cite book | last1=Pilli | first1=E. | last2=Berti | first2=A. | title=Forensic DNA Analysis: Technological Development and Innovative Applications | publisher=Apple Academic Press | year=2021 | isbn=978-1-000-06454-4 | url=https://books.google.com/books?id=A9MREAAAQBAJ&pg=PA207 | access-date=2024-05-22 | page=207}} "Several research groups have demonstrated that females have a darker eye color than males, given the same SNP profile (Martinez-Cadenas et al., 2013; Pietroni et al., 2014; Pospiech et al., 2016)."</ref> [[Sex]] is therefore a major factor in the expression of eye color genotypes.<ref name="Martinez-Cadenas Peña-Chilet Ibarrola-Villava Ribas 2013 pp. 453–460" /> One study suggested that women's higher levels of the sex hormone [[estrogen]] may explain why women tend to have darker eyes than men.<ref name="x873">{{cite journal | last1=Hernando | first1=Barbara | last2=Ibarrola-Villava | first2=Maider | last3=Fernandez | first3=Lara P. | last4=Peña-Chilet | first4=Maria | last5=Llorca-Cardeñosa | first5=Marta | last6=Oltra | first6=Sara S. | last7=Alonso | first7=Santos | last8=Boyano | first8=Maria Dolores | last9=Martinez-Cadenas | first9=Conrado | last10=Ribas | first10=Gloria | title=Sex-specific genetic effects associated with pigmentation, sensitivity to sunlight, and melanoma in a population of Spanish origin | journal=Biology of Sex Differences | volume=7 | issue=1 | date=2016 | page=17 | issn=2042-6410 | doi=10.1186/s13293-016-0070-1 | doi-access=free | pmid=26998216 | pmc=4797181 | quote=The results of this study suggest that there are indeed sex-specific genetic effects in human pigmentation, with larger effects for darker pigmentation in females compared to males. A plausible cause might be the differentially expressed melanogenic genes in females due to higher oestrogen levels. These sex-specific genetic effects would help explain the presence of darker eye and skin pigmentation in females, as well as the well-known higher melanoma risk displayed by males.| hdl=10810/32358 | hdl-access=free }}</ref> 

People of European descent show the greatest variety in eye color of any population worldwide. Recent advances in [[ancient DNA]] technology have revealed some of the history of eye color in Europe. Through the analysis of ancient DNA, a 2020 study published in ''Experimental Dermatology'' suggested that the common gene for blue eye color likely originated in the [[Near East]] and arrived in Europe around 42,000 years ago, after the exodus [[Recent African origin of modern humans|out of Africa]].<ref name="Cberg">{{cite journal |last1=Hanel |first1=Andrea |last2=Carlberg |first2=Carsten |title=Skin colour and vitamin D: An update |journal=Experimental Dermatology |date=September 2020 |volume=29 |issue=9 |pages=864–875 |doi=10.1111/exd.14142 |pmid=32621306 |s2cid=220335539 |language=en |issn=0906-6705|doi-access=free }} "The genetic history of today's European populations is based on continuous migrations over the past 40 000 years. Homo sapiens arrived in Europe from Near East some 42 000 years ago.[48, 49] Like in their African origin, these humans had dark skin but due to variations of their OCA2 gene (causing iris depigmentation) many of them had blue eyes[48,50] (Figure 2, left)." Figure 2: "Phenotype information was retrieved from supplementary files of the according publications or additionally assessed following the instructions of HirisPlex-S, which is a forensic DNA phenotyping tool based on an array of different marker SNPs providing additional support to the SNPs of the genes SLC24A5, SLC45A2 and OCA2."</ref>

There is evidence that as many as 16 different genes could be responsible for eye color in humans; however, the main two genes associated with eye color variation are ''[[OCA2]]'' and ''[[HERC2]]'', and both are localized in [[chromosome 15]].<ref name=pmid20944644/>

The gene ''OCA2'' ({{OMIM|203200||short}}), when in a variant form, causes the pink eye color and [[hypopigmentation]] common in human [[Albinism in humans|albinism]]. (The name of the gene is derived from the disorder it causes, oculocutaneous albinism type II.) Different SNPs within ''OCA2'' are strongly associated with blue and green eyes as well as variations in [[freckling]], [[Mole (skin marking)|mole]] counts, [[hair color|hair]] and [[Human skin color|skin tone]]. The polymorphisms may be in an ''OCA2'' [[regulatory sequence]], where they may influence the expression of the gene product, which in turn affects pigmentation.<ref name="OCA2" /> A specific mutation within the ''HERC2'' gene, a gene that regulates ''OCA2'' expression, is partly responsible for blue eyes.<ref name="Kayser">{{cite journal |title=Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene |journal=Am. J. Hum. Genet. |volume=82 |issue=2 |pages=411–23 |year=2008 |pmid=18252221 |pmc=2427174 |doi=10.1016/j.ajhg.2007.10.003 |last1=Kayser |first1=Manfred |last2=Liu |first2=Fan |last3=Janssens |first3=A. Cecile J.W. |last4=Rivadeneira |first4=Fernando |last5=Lao |first5=Oscar |last6=Van Duijn |first6=Kate |last7=Vermeulen |first7=Mark |last8=Arp |first8=Pascal |last9=Jhamai |first9=Mila M. |last10=Van Ijcken |first10=Wilfred F.J. |last11=Den Dunnen |first11=Johan T. |last12=Heath |first12=Simon |last13=Zelenika |first13=Diana |last14=Despriet |first14=Dominiek D.G. |last15=Klaver |first15=Caroline C.W. |last16=Vingerling |first16=Johannes R. |last17=De Jong |first17=Paulus T.V.M. |last18=Hofman |first18=Albert |last19=Aulchenko |first19=Yurii S. |last20=Uitterlinden |first20=Andre G. |last21=Oostra |first21=Ben A. |last22=Van Duijn |first22=Cornelia M. |display-authors=8 }}</ref> Other genes implicated in eye color variation are [[SLC24A4]]<ref name="Sulem">{{cite journal |title=Genetic determinants of hair, eye and skin pigmentation in Europeans |journal=Nat. Genet. |volume=39 |issue=12 |pages=1443–52 |year=2007 |pmid=17952075 |doi=10.1038/ng.2007.13 |last1=Sulem |first1=Patrick |last2=Gudbjartsson |first2=Daniel F |last3=Stacey |first3=Simon N |last4=Helgason |first4=Agnar |last5=Rafnar |first5=Thorunn |last6=Magnusson |first6=Kristinn P |last7=Manolescu |first7=Andrei |last8=Karason |first8=Ari |last9=Palsson |first9=Arnar |last10=Thorleifsson |first10=Gudmar |last11=Jakobsdottir |first11=Margret |last12=Steinberg |first12=Stacy |last13=Pálsson |first13=Snæbjörn |last14=Jonasson |first14=Fridbert |last15=Sigurgeirsson |first15=Bardur |last16=Thorisdottir |first16=Kristin |last17=Ragnarsson |first17=Rafn |last18=Benediktsdottir |first18=Kristrun R |last19=Aben |first19=Katja K |last20=Kiemeney |first20=Lambertus A |last21=Olafsson |first21=Jon H |last22=Gulcher |first22=Jeffrey |last23=Kong |first23=Augie |last24=Thorsteinsdottir |first24=Unnur |last25=Stefansson |first25=Kari |s2cid=19313549 |display-authors=8 }}</ref> and [[Tyrosinase|TYR]].<ref name="Sulem" /> A 2010 study of eye color variation in hue and saturation values using high-resolution digital full-eye photographs found three new loci for a total of ten genes, allowing the explanation of about 50% of eye color variation.<ref>{{Cite journal |doi=10.1371/journal.pgen.1000934|pmid = 20463881|pmc = 2865509|title = Digital Quantification of Human Eye Color Highlights Genetic Association of Three New Loci|journal = PLOS Genetics|volume = 6|issue = 5|pages = e1000934|year = 2010|last1 = Liu|first1 = Fan|last2 = Wollstein|first2 = Andreas|last3 = Hysi|first3 = Pirro G.|last4 = Ankra-Badu|first4 = Georgina A.|last5 = Spector|first5 = Timothy D.|last6 = Park|first6 = Daniel|last7 = Zhu|first7 = Gu|last8 = Larsson|first8 = Mats|last9 = Duffy|first9 = David L.|last10 = Montgomery|first10 = Grant W.|last11 = MacKey|first11 = David A.|last12 = Walsh|first12 = Susan|last13 = Lao|first13 = Oscar|last14 = Hofman|first14 = Albert|last15 = Rivadeneira|first15 = Fernando|last16 = Vingerling|first16 = Johannes R.|last17 = Uitterlinden|first17 = André G.|last18 = Martin|first18 = Nicholas G.|last19 = Hammond|first19 = Christopher J.|last20 = Kayser|first20 = Manfred | doi-access=free }}</ref>
 
{| class="wikitable"
|-
! Gene name
! Effect on eye color
|-
| [[OCA2]]
| Associated with [[melanin]] producing cells. Central importance to eye color.
|-
| [[HERC2]]
| Affects function of OCA2, with a specific mutation strongly linked to blue eyes.
|-
|[[SLC24A4]]
| Associated with differences between blue and green eyes.<ref name="Sulem" />
|-
|[[Tyrosinase|TYR]]
| Associated with differences between blue and green eyes.<ref name="Sulem" />
|}

Blue eyes with a brown spot, green eyes, and gray eyes are caused by an entirely different part of the genome.