Heterochromia

[TheEtherealChemist]

I was just wondering whether anyone could explain what causes Heterochromia? I've recently started listening to Rise Against, and their singer has one brown eye and one blue. I don't know if this is the right forum, but I was hoping someone could furnish me with an explanation of the genetics behind it. Thanks in advance!

[jimmydasaint]

Hi SHA. This is the right Forum The condition is apparently caused by the presence of a dominant gene, or as a result of a benign tumour after birth, or from accidents, e.g. to David Bowie. The pigmentation is caused by excess or too little melanin.

 

Lost Melanocytes

Getting color in hair, skin, or eyes is surprisingly complex. Once a melanocyte develops, it often needs to migrate to its proper place. Sometimes melanocytes get lost on the way to where they should end up.

 

When a melanocyte doesn’t make it to the right place, that spot will not have color. If it is skin or hair, it will be a white spot. If it is the eye, then the eye will be blue.

 

Many factors can affect a melanocyte’s well being. For example, an injury during development can cause them to die off. And there are certain diseases that can cause a melanocyte not to develop or migrate to the right spot. The most common is called Waardenburg syndrome.

 

Eye Color Genetics

Recent work points to the OCA2 gene as the key gene in deciding between brown and other color eyes. The green eye gene has not yet been found.

 

 

People with Waardenburg syndrome sometimes having a shock of white hair or two different colored eyes. It is also why some dog breeds can sometimes have two different colored eyes.

 

Besides lost melanocytes, a less common way to end up with two different colored eyes is when an eye color gene works in one eye but not the other. Two ways that this can happen are called mosaicism and chimerism.

 

Chimeras and Mosaics

Both chimeras and mosaics have some cells in their body with one set of DNA and other cells with a different set of DNA. In chimeras, the DNAs are as different as any two siblings’ DNA (which makes sense since chimeras are fused fraternal twins). The DNA difference in mosaics is much smaller. Often the difference can only be at a single gene.

 

A chimera can have two different colored eyes just like any two siblings can—because each cell has different eye color genes. A mosaic can have two different colored eyes if the DNA difference happens to be in an eye color gene.

 

There are many other possible reasons for having two different colored eyes. For example, David Bowie's different eye colors comes from an injury that caused one pupil to be permanently dilated. Another idea about how this can happen is if an early viral infection while in the womb turns an eye color gene on or off in just one eye. Occasionally it can be a sign

 

 

 

Read more at Suite101: Having Two Different Colored Eyes: Heterochromia is Caused by Genetics, Injury and/or Disease http://humangenetics.suite101.com/article.cfm/having_two_different_colored_eyes#ixzz0ucBa1sev

Link

Edited July 25, 2010 by jimmydasaint

[TheEtherealChemist]

Thank you so much, that was a great explanation, and I really appreciate you taking the time to provide it!

Edited July 24, 2010 by Shadow Haloed Angel

[jimmydasaint]

As for the genetics, some melanocyte problems in the mouse model shows recessive, co-dominant and dominant mutations. These mutations could be deletions or substitutions causing shorter proteins than the normal or wild-type protein.

 

This paper needs careful reading but makes a bit of sense:

 

In eukaryotes, the messenger RNA made from the DNA in the chromosome is processed by splicing which is akin to a chopping and reassemblng of the message in the correct order before the ribosomes change it into protein. The bits of message which are chopped out are called introns and the bits which are translated into protein are called exons. For example this statement can be processed to make sense:

 

MUM, WHO IS THE SCYLLA TO MY RELUCTANT CHARYBDIS, AND BESIDES, CAUSES ME NO END OF GRIEF, LOOKED BEAUTIFUL IN HER BLUE DRESS can be processed to cut out details (introns) thus:

 

MUM LOOKED BEAUTIFUL IN HER BLUE DRESS (exons). This final 'message' can then be translated into 'protein'.

 

In the course of analysis of ENU-induced mutations in Syrian hamsters, a novel dominant anophthalmic white mutant (WhV203) with hearing loss was recovered. Because of this phenotype and a close linkage to the Tpi gene, the Mitf gene was considered as a candidate gene. In the Mitf cDNA, a deletion of 76 bp covering the entire exon 7 was detected. Further molecular analysis revealed a T A exchange 16 bp upstream of the end of intron 6, leading to skipping of exon 7. These 16 bp at the end of intron 6 are identical in hamster, rat, mouse, and humans, indicating high conservation during evolution and a functional importance in splicing. Since the loss of exon 7 changes the open reading frame of the MITF transcript, translation will be stopped after 10 new amino acids. The truncated protein is predicted to contain only a part of the basic region and will miss the two helical domains and the leucine zipper. The WhV203 mutation in the Syrian hamster affects the same functional domains of the Mitf transcription factor as the human R124X mutation, causing human Waardenburg syndrome type II. Therefore, the WhV203 hamster mutant provides a novel model for this particular syndrome.

Link

 

Remember, this is only one genetic disorder that causes melanocyte problems and that injury or infections can also cause heterochromia.

 

Abstract

Waardenburg syndrome type 2 (WS2) is a dominantly inherited syndrome of hearing loss and pigmentary disturbances. We recently mapped a WS2 gene to chromosome 3p12.3-p14.1 and proposed as a candidate gene MITF, the human homologue of the mouse microphthalmia (mi) gene. This encodes a putative basic-helix-loop-helix-leucine zipper transcription factor expressed in adult skin and in embryonic retina, otic vesicle and hair follicles. Mice carrying mi mutations show reduced pigmentation of the eyes and coat, and with some alleles, microphthalmia, hearing loss, osteopetrosis and mast cell defects. Here we show that affected individuals in two WS2 families have mutations affecting splice sites in the MITF gene.

Link

Edited July 26, 2010 by jimmydasaint

[TheEtherealChemist]

thanks so much!