Overo Lethal White Syndrome Update

The same researchers who identified the gene mutation that causes deadly overo lethal white syndrome (OLWS) have more accurately determined the coat patterns associated with OLWS in newborn foals. The effects of OLWS are wide-reaching, as it has been found in Paints, Miniature Horses, half-Arabians, Thoroughbreds, and cropout Quarter Horses (Quarter Horse foals born with too much white to be accepted into the breed's registry).

Elizabeth M. Santschi, DVM, Dipl. ACVS, clinical associate professor at the University of Wisconsin's School of Veterinary Medicine, was a principal researcher in the University of Minnesota studies. Overo lethal white syndrome has been a frustrating problem for breeders, as the condition is always fatal. "Basically you get this all-white foal born apparently healthy, but he never passes feces and he eventually colics and dies," explains Santschi. "There's nothing you can do. As a surgeon, I always want to do something, and there's nothing I can do (for OLWS foals). The only way to avoid this condition is to not breed them."

This led to studies examining the genetics behind OLWS. The condition was associated with its namesake overo coloring in carrier parents (characterized by white coloration of the abdomen that does not cross the dorsal midline between the withers and tail). Symptoms are similar to a genetic condition (Hirschprung disease) that appears in humans and rodents, so Santschi's group targeted the same gene in the horse. In 1998, the group revealed in Mammalian Genome that a mutation of the endothelin receptor B (EDNRB) gene was associated with OLWS. Lethal white foals have two copies of the defective allele (two alleles make up a gene, one from each parent), while their healthy carrier parents have one, and non-carrier horses have none. They deduced that if one-copy horses were not bred to each other, OLWS would never occur. "The beauty of it is, you can test your horses before breeding to see if you have a carrier," says Santschi.

But not all overo horses are phenotypically the same, as there are four distinct overo subtypes (frame, calico, sabino, and splashed white). And not all overos produce affected foals, which left questions about which subtypes are affected. The latest study included 1,000 horses from farms that had never experienced OLWS, and farms that had high incidence of the syndrome. "We took photos and DNA samples to try and determine how this mutation determines coat color or white patterning," explains Santschi.

They found that in heterozygotes (horses with one normal and one defective allele in the EDNRB gene), the mutation is usually responsible for a frame overo pattern (see www.apha.com/association/PDFFiles/01geneticsguide.pdf). Since frame overos' characteristic pattern can be altered through breeding to horses with other patterns, accurate visual inspection of carriers of the defective gene can be difficult due to blending of the patterns.

It was also found that other genes control both overo and tobiano (the other main type of white patterning recognized by the American Paint Horse Association) patterning besides EDNRB. Therefore, researchers deduced that determination of EDNRB genotype by use of a DNA-based test is the only way to determine with certainty whether a white-patterned horse can produce a foal affected with OLWS.

Santschi added, "If you can't tolerate a lethal white, you should test your horses."

About the Author

Stephanie L. Church, Editor-in-Chief

Stephanie L. Church, Editor-in-Chief, received a B.A. in Journalism and Equestrian Studies from Averett College in Danville, Virginia. A Pony Club and 4-H graduate, her background is in eventing, and she is schooling her recently retired Thoroughbred racehorse, Happy, toward a career in that discipline. She also enjoys traveling, photography, cycling, and cooking in her free time.

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