1. Is Blue Really Blue? Understanding Eye Color

2. Eye Color Image courtesy of the National Eye Institute, National Institutes of Health Eye color depends on the amount of pigment (melanin) in the iris. Blue= very little melanin. Green and Gray= intermediate amounts of melanin. Brown= much more melanin Albino= no melanin.

3. Different Models Over time, there have been different models proposed to explain inheritance. Over the next few slides, we will review –One Gene Model –Two Gene Model –Molecular / SNP Model

4. From: Giffiths et al Intro to Genetic Analysis One Gene Model Blue eye color is controlled by one gene. It is a recessive, autosomal gene. Cause of much consternation, because its by no means completely true.

5. Two Gene Model

7. There’s a lot this model can’t explain, beginning with gray and hazel eyes. Or how blue-eyed parents can have a brown-eyed child. And they can. Eye color is controlled by A Blue Gene (BEY2) on Chromosome 15. At the Blue locus you could be… Blue (b) Brown (B) A Green Gene (GEY) on Chromosome 19. At the Green locus you could be Green (G) Blue (b)

8. From: Eiberg et al 2008 Problem: What is blue?

9. From: Eiburg et al 2008 Model at the Molecular Level BEY2=OCA2. It’s a real gene. Encodes the P protein that is a precursor to melanin. Several studies found associations between the non-coding regions of OCA2 and blue eye color. But they weren’t perfect associations.

10. From: Eiburg et al 2008 Model at the Molecular Level In 2008, people were surprised to find that there was another gene that was PERFECTLY associated with blue eyes. It is very close (neighboring) OCA2. It does not encode melanin. The nearby gene is called HERC2 and it has a SNP that is perfectly associated with blue eyes in the study population.

11. From: Eiburg et al 2008 Model at the Molecular Level What’s going on? Do blue-eyed people have functional melanin genes? How do you get little melanin in the eyes, but plenty elsewhere? You need to be able to turn the gene off in the eyes. REGULATORY GENE!

12. What is a SNP? A Single Nucleotide Polymorphism 1.A marker 2.A mutation. The single base difference can be the cause of a “broken” gene that leads to a disorder. A block of SNPs that are inherited together is called a haplotype.

13. From: Eiburg et al 2008 Model at the Molecular Level HERC2 binds transcription factors, and is thought to be a gene that regulates OCA2. This makes sense. And there is only one real distinction– Blue and Non- blue.

14. Lightcycler Output: eye color Eye color assay: rs12913832 in HERC2 gene Blue (G) Non-Blue (A) We can use Real-time PCR to detect the SNP in the HERC2 gene.