I’ll be taking a break from blogging over the next month as the “egg” (or is that the chicken?) will be hatching. As you do, when about to have a baby, I’ve been thinking a bit about inheritance lately – what colour eyes or hair will my baby have, how tall, who will he/she take after? The questions are endless really (and no we DONT know the sex!).
Being a geneticist, I figured the answers to at least some of these questions must be relatively well worked out. Eye colour for starters – we all know brown eyes are dominant to blue, right? And if you google “eye colour inheritance” you can find any number of “eye colour calculators” that will work out the likely eye colour of your offspring. I tried to use one of these and immediately ran into a problem – even the most sophisticated one I could find only allowed brown, blue or green as eye colours. Well, my eyes are hazel (grey/green with a brown ring around the pupil). Does this count as green? And my partners eyes are not exactly blue or green, they are kind of greyish-greenish-blueish with a tendency to change colour depending on his clothes and the light. So having fallen at the first hurdle, I began to suspect that eye colour might be a whole lot more complicated than what you learn at school.
And it turns out that it is – eye colour is a polygenic trait, which means there are multiple genes that interact to produce the colour. How many genes there are, where they are and what they do exactly is only partially known.
Eye colour is determined by the amount and distribution of melanin in the iris. Brown eyes contain more melanin than green eyes, while blue eyes have very little melanin. The old textbook explanation that brown is dominant to green and both are dominant to blue does generally hold true, but not always, and is too simplistic to explain the multitude of variations on grey, blue, green and brown. Geneticists have been modelling the inheritance of eye colour since the late 19th century, but originally described inheritance along the simple Mendelian dominant/recessive lines I described above. It didn’t take long for exceptions to this rule to become apparent (like two blue eyed parents having a brown eyed child) and it became obvious that there must be more than one gene involved.
In the 1980s chromosome mapping techniques were developed which enabled researchers to identify particular chromosomal regions (or loci) that are associated with inheritance of particular traits. A locus associated with green eye colour (named Gey) was mapped to chromosome 19, and a locus associated with brown/blue eye eye colour (named Bey) was mapped to chromosome 15. These “loci” are not genes as such, but they are regions of the chromosome that contain the genes likely to play a role in eye colour. Many of the textbook explanations (and online calculators) for eye colour will tell you that there are 2 variants (alleles) for each of these loci – a green (dominant) and blue (recessive) allele at Gey, and a brown (dominant) and blue (recessive) allele at Bey. This is a useful model for demonstrating how inheritance of a polygenic trait works, and in the case of eye colour it does explain some common patterns of inheritance. But there are clearly additional alleles and additional genes at work that are only now beginning to be identified.
The Bey locus has now been identified as a gene called OCA2. This gene codes for a protein that stimulates the melanin-producing cells in the eye to mature and well, produce melanin. OCA2 now looks to be the major determinant of eye colour, with some recent research estimating that this gene alone is responsible for about 74% of the variation in human eye colour. There are far more than just two variant forms of this gene – dozens of alleles have now been identified, many differing by only a few changes in their DNA sequence. A 2006 study found that some of these changes are highly diagnostic for particular eye colours – in fact, eye colour can be predicted reasonably well (but not entirely) from a person’s genotype at OCA2. With the availability of human genome sequences, more new genes associated with eye colour are being discovered, but how these genes interact with OCA2, and exactly how much they contribute to eye colour is yet to be determined.
So what colour will my baby’s eyes be? After all my research I’m really no closer to an answer, but I’m guessing probably some variation on green. I’ll be sure to let you know.
References (these appear to be free to access):
Sturm RA and Larsson M (2009) Genetics of human iris colour and patterns. Pigment Cell and Melanoma Research 22: 544-562. DOI: j.1755-148X.2009.00606.x
Duffy DL, Montgomery GW, Chen W, Zhao ZZ, Le L, James MR, Hayward NK, Martin NG, Sturm RA (2006). A three single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. American Journal of Human Genetics 80: 241-52. DOI: 10.1086/510885