LETHAL WHITE DISORDER

Tavishi

Confession: I am a born and raised horse girl. This is, actually, how I managed to fracture my femur at the ripe old age of ten years old. I do have some pretty sick pins that were put into the bone to aid in the healing process, which is quite cool to think about.

Anyways, I like horses!

I don't ride anymore, but when I am back in Phoenix, I enjoy spending my time volunteering at this incredible horse rescue: Healing Hearts horse rescue! Highly recommend checking them out, they're a wonderful organization.

me and Lucky! Lucky is one of my favorite horses of all time, he's such a sweet scaredy little man. He also loves himself a little pumpkin spice treat. which is very white girl of him. go white girl go

Horses are artificially selected to all get out- there are tons of breeds and colors. Horse people love to have horses of different colors and origins.

Anyways, horses have some pretty cool genetics behind their appearances. The molecule that colors both skin and hair is melanin. Melanin comes in two flavors: pheomelanin, or a red/yellow pigment, and eumelanin, or a brown-black pigment. These two pigments work together to cooperatively create different shades of color.

There are two main genes that control the expression of melanin throughout a horse: MC1R and ASIP.

MC1R (melanocortin 1 receptor).

This gene is responsible for the expression of red and black pigment. It is also called extension! When activated, MC1R signals pigment cells to produce black pigment. This is the dominant allele (E).

When inactive, MC1R is nonfunctional, and a solid red color is produced, or chestnut. This is the recessive allele (e).

ASIP (agouti signaling protein)

This gene interacts with MC1R by blocking the production of black pigment.

The dominant allele, A, blocks pigment production, whereas the recessive allele, a, is nonfunctional.

A horse with the genotypes EE or Ee should, in theory, be fully black. UNLESS it has the ASIP genotype aa, which would mean no black pigment is produced.

If the horse with the genotype EE/Ee is heterozygous for ASIP, or Aa, it would produce a horse that is bay. A bay horse is a mix between chestnut and black, where the black pigment is produced in points. Bay encompasses a lot of different coat colors, and is the most common horse coat.

Important question: how do we get from bay to allll of those different colors? So, fun fact. There are more genes.

Just like ASIP can cancel out MC1R's opinions, different genes can affect how much of the pigment makes it from the melanocyte to the hairs.

Take, for example, the Dun gene.

dun dun dun!!

The dun gene is also called TBX3, and is found on chromosome 8. It dilutes both eumelanin and pheomelanin. A horse with a dominant genotype for Dun (DD or Dd) would be light colored, whereas a horse with a recessive genotype (dd) would be normally colored.

this horse here is recessive for Dun, recessive for MC1R, and we don't care about its ASIP genotype

Now, if we take this horse above, and Dun it up, we get this:

RED DUN!

Anyways, I'm Dun with this post.

.

.

.

Just kidding, I needed to add in another pun, of course. (or should I say Dun?)

We still haven't gotten to the title of the post!! OR, MOST IMPORTANTLY, SEAL BAY! Seal bay is objectively the BEST horse color.

he seal bay !!

Seal bay is thought to be caused by another ASIP allele, but hasn't been proven yet. It's not quite black, but it's also not quite a bay at all. We have no idea otherwise what the genetics behind seal bay is. I am content with these answers, though.

Speaking of horses and seals, the gray seal is sometimes called the horsehead seal because of their long snout. Their scientific name, Halichoerus grypus, translates to hook-nosed sea pig. I know Latin, so I can confirm grypus means hook-nosed. Greek speakers (Greakers?), can you confirm the genus name.

Ok back to the topic. That all should be a sidebar.

Lethal white disorder is a congenital disorder in foals which results in stillbirths or deaths of foals shortly after birth. The foal is a homozygote for the frame allele on the gene EDNRB. This gene is essential for the development of the enteric nervous system, which controls the digestive processes. This mutation results in a poorly developed colon and an inability to pass fecal matter.

On the other hand, heterozygotes, or those with only one copy of the frame allele, go on to live a perfectly healthy life, and instead have white splash patterns:

Foals born with lethal white syndrome are, as the name suggests, almost entirely white or completely white. They also have blue eyes.

The reason that the horse is born white comes down to the neural crest cells. As I mentioned, the enteric nervous system does not develop in foals. The enteric nervous system is a branch of the peripheral nervous system isolated to the digestive tract- it controls peristaltic movement.

Now, the peripheral nervous system develops from a line of cells in utero called the neural crest cells.

The neural crest cells ALSO give rise to pigment cells. Heterozygotes experience some failure of neural crest cells to migrate- hence the spots of splashed white.

Homozygotes experience this failure to a much greater extent, such that very few pigment cells migrate at all, if any, and the enteric nervous system fails to develop.

This mutation comes down to a mutation of a SINGLE amino acid. In the place of an isoleucine, there is, instead, a lysine. It's honestly devastating but also terrifying that a mistake that small can be the difference between life and death. Such is the work of genetics, though. I think one of the most fascinating things about learning about molecular biology at all is realizing how fragile the balance the body hangs in is. It makes the vibrance, diversity, and persistence of Animalia all the more miraculous.