Is Blue Really Blue?
Understanding
Eye Color
Eye Color
• 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.
Image courtesy of the National Eye Institute, National Institutes of Health
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
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.
From: Giffiths et al Intro to Genetic Analysis
Two Gene Model
Two Gene Model
Two Gene Model
Eye color is controlled by
A Blue Gene (BEY2) on
Chromosome 15.
A Green Gene (GEY) on
Chromosome 19.
At the Blue locus you could be…
At the Green locus you could be
Blue (b)
•
•
Brown (B)
Green (G)
Blue (b)
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.
Problem: What is blue?
From: Eiberg 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.
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.
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!
From: Eiburg et al 2008
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.
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 Nonblue.
From: Eiburg et al 2008
Lightcycler Output: eye color
We can use Real-time PCR to detect the SNP in the
HERC2 gene.
Eye color assay: rs12913832 in HERC2 gene
Blue
(G)
Non-Blue
(A)