Friday, December 22, 2006


Genetics of eye colour unlocked

A study by researchers from The University of Queensland's Institute for Molecular Bioscience (IMB) and the Queensland Institute of Medical Research is the first to prove conclusively that there is no single gene for eye colour.

Instead, it found that several genes determine the colour of an individual's eyes, although some have more influence than others.

"Each individual has two versions of a gene, inheriting one from each parent, and these versions can be the same as each other or different," Dr Rick Sturm, the IMB researcher who led the study, said.

"It used to be thought that eye colour was what we call a simple Mendelian recessive trait - in other words, brown eye colour was dominant over blue, so a person with two brown versions of the gene or a brown and a blue would have brown eyes, and only two blues with no brown could produce blue eyes.

"But the model of eye colour inheritance using a single gene is insufficient to explain the range of eye colours that appear in humans. We believe instead that there are two major genes - one that controls for brown or blue, and one that controls for green or hazel - and others that modify this trait.

"So contrary to what used to be thought, it is possible for two blue-eyed parents to have a brown-eyed child, although this is not common."

Dr Sturm likens the system to a light bulb.

"The mechanism that determines whether an eye is brown or blue is like switching on a light, whereas an eye becoming green or hazel is more like someone unscrewing the light bulb and putting in a different one."

The study was carried out to clarify the role of the OCA2 gene in the inheritance of eye colour and other pigmentary traits associated with skin cancer risk in white populations, and examined nearly 4000 adolescent twins, their siblings and their parents over five years.

Source: University of Queensland PR "The eyes have it on multiple gene question" February 20 2007


Based on "A Three-Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation"

David L. Duffy, Grant W. Montgomery, Wei Chen, Zhen Zhen Zhao, Lien Le, Michael R. James, Nicholas K. Hayward, Nicholas G. Martin, and Richard A. Sturm

Am. J. Hum. Genet., 80:241-252, 2007


We have previously shown that a quantitative-trait locus linked to the OCA2 region of 15q accounts for 74% of variation in human eye color. We conducted additional genotyping to clarify the role of the OCA2 locus in the inheritance of eye color and other pigmentary traits associated with skin-cancer risk in white populations. Fifty-eight synonymous and nonsynonymous exonic single-nucleotide polymorphisms (SNPs) and tagging SNPs were typed in a collection of 3,839 adolescent twins, their siblings, and their parents. The highest association for blue/nonblue eye color was found with three OCA2 SNPs: rs7495174 T/C, rs6497268 G/T, and rs11855019 T/C (P values of 1.02 x 10-61, 1.57 x 10-96, and 4.45 x 10-54, respectively) in intron 1. These three SNPs are in one major haplotype block, with TGT representing 78.4% of alleles. The TGT/TGT diplotype found in 62.2% of samples was the major genotype seen to modify eye color, with a frequency of 0.905 in blue or green compared with only 0.095 in brown eye color. This genotype was also at highest frequency in subjects with light brown hair and was more frequent in fair and medium skin types, consistent with the TGT haplotype acting as a recessive modifier of lighter pigmentary phenotypes. Homozygotes for rs11855019 C/C were predominantly without freckles and had lower mole counts. The minor population impact of the nonsynonymous coding-region polymorphisms Arg305Trp and Arg419Gln associated with nonblue eyes and the tight linkage of the major TGT haplotype within the intron 1 of OCA2 with blue eye color and lighter hair and skin tones suggest that differences within the 5' proximal regulatory control region of the OCA2 gene alter expression or messenger RNA-transcript levels and may be responsible for these associations.


*Rick Sturm is author of the Trends in Genetics paper "A golden age of human pigmentation genetics"

Volume 22, Issue 9 , September 2006, Pages 464-468


The zebrafish golden mutation is characterized by the production of small and irregular-shaped melanin granules, resulting in a lightening of the pigmented lateral stripes of the animal. The recent positional cloning and localization of the golden gene, combined with genotype-phenotype correlations of alleles of its human orthologue (SLC24A5) in African-American and African-Caribbean populations, provide insights into the genetic and molecular basis of human skin colour. SLC24A5 promotes melanin deposition through maturation of the melanosome, highlighting the importance of ion-exchange in the function of this organelle.

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