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Overo Lethal White Syndrome (OLWS)

Overo Lethal White Syndrome (OLWS)

What could be worse than having your mare give birth to a gorgeous, pure white foal, and to find out it is as good as dead. This is what has plagued the APHA industry for many years. Once the foal is born, it can take up to several hours or even a day before there are signs that something is wrong. For one, the foal will not pass any fecal matter. Abdominal cramping begins and the foal will start to colic. Basically, the foal has an un-relievable constipation. Rolling around only further worsens the situation by causing the foals intestines to twist, putting it in even more pain. A vet should be contacted in the event that your paint mare produces a white foal so they can determine is they have Lethal White or not and euthanize it if it does. Lethal White is incurable. Attempts in the past to surgically correct the problem have failed. A foal that young does not have the immunity to withstand an operation. In most cases, a pure white foal will be affected, but there have been instances where healthy white foals have been born. Don't make any assumptions until you have called your vet.

Although other breeds such as: thoroughbreds, miniatures, half-arabians(pinto arabs), and quarter horses(crop-out) are capable of producing/carrying Lethal White, it predominantly occurs in paints, originating from overos. If a tobiano has an overo in its bloodlines, then there is a possibility that the gene could have been passed on. Many paints do carry the gene, but only when crossed with another carrier is it possible to produce a Lethal White foal. The probability of a Lethal White being produced in that instance is only 25%. Even though it is a one in four possibility, precautions should be taken when breeding. Finding out how to have your breeding stock tested is recommended.

How DNA comes into play:

DNA (Deoxyribonucleic Acid) is what makes anyone and anything what it is. It is what determines eye color, height, set-weight, skin/coat color. DNA is made up of nucleotides, phosphates and sugar. Nucleotides produce amino acids and amino acids are the building blocks of proteins. In DNA, nucleotides are coded in triplets called codons, each codon coding for a specific amino acid. There are 22 types of amino acids which can be coded. There are only 4 different nucleotides: T-thymine C-cytosine A-adenine G-guanine. A ribbon of DNA contains millions of these nucleotides repeated over and over in different orders, for example: ATGCCGGGTCATTGAACT... and so on. In this example, the codons would be: ATG CCG GGT CAT TGA ACT. (eg: ATG would code for the amino acid Tyrosine, CCG for Proline, and so on) Millions of amino acids form a protein. When a body needs an enzyme or receptor produced (enzymes and receptors are proteins) DNA is called upon to code and select the proper amino acids to produce this specific protein.

Now that I've given you DNA 101, I will explain what proteins have to do with Lethal White. Organisms have the nucleotides in their DNA set up in a specific orders, we aren't just born with these things randomly put together, they are put together specifically so any living being can function properly. When a mutation occurs within codons, the production of a specific amino acid in a protein is changed; therefore, altering the entire protein itself. Take lactose intolerant people for example. They are NOT allergic to dairy, their bodies simply do not produce the right enzyme to digest lactose, causing the body to react to its presence as if it's harmful. Why do they not produce this enzyme? Because in their DNA, a nucleotide is out of place, completely altering the protein to be produced. In a Lethal White foal, there is a mutation with the codon(118) that is supposed to aid in the production of the endothelin receptor B. The amino acid Isoleucine is supposed to be made, but instead the mutation causes the amino acid Lysine to be produced. Just one amino acid out of place forms an entirely different protein. This miniscule alteration in the DNA is what gives us Lethal White.

Lethal White is a recessive gene, meaning that it is masked by the dominant 'normal' gene. The dominant gene prevents the recessive gene from showing. When there are two recessive genes (homozygote), masking doesn't occur. A horse that is a carrier will test positive for Lysine118.

Now for our next question.

Why does the absence of the Endothelin Receptor B cause Lethal White?

Briefly: The absence of this protein during the embryotic stages of the foal prevents: the migration and causes proliferation of stem cells from the neural crest. Stem cells are necessary for development of any tissues in the body, including nerve cells. Nerve cells are needed to send messages throughout the body. The lack of these nerve cells prevents the brain from sending message to the tissues in the intestines. An undeveloped colon occurs. The undeveloped colon either: does not connect to the rectum, or; the peristalsis does not occur in the colon. Peristalsis is the movement in the bowels which moves fecal matter along during digestion, without this, major blockage occurs. In either case, it eventually lead to intestinal eruption. This is an equine version of Hirschsprung Disease, which occurs in humans.

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