byahair-mar04.pdf

By REBECCA OVERTON

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PAINT HORSE JOURNAL

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MARCH 2003

Consider a hair.

If it gets in your eye, you want it out.

If it lands on your clothes, you want it

off. Each year, balding men spend

millions of dollars in the hope of re-

plenishing the diminishing supply on

their heads.

To a Paint Horse breeder, a hair can

mean the difference between holding

your breath for 11 months to see if a

foal will be born with Overo Lethal

White Syndrome (OLWS), or know-

ing you made a genetic cross that en-

sures you won’t get a foal with the

dreaded disease.

Using hair samples from a horse’s

mane or tail, geneticists at the Uni-

versity of California–Davis can deter-

mine if a horse is at risk for producing

lethal white foals. The test reveals

whether a horse carries the mutation

associated with lethal white syndrome

by looking at DNA extracted from a

hair follicle.

Offered by the Veterinary Genet-

ics Lab at the UC Davis School of

Veterinary Medicine, the test costs

$50 and can be ordered by com-

pleting a form and returning it to

the lab.

The test requires 25–30 samples of

hair, which must be pulled, not cut,

so that the roots are intact. A horse

needs to be tested only once. Results

are confidential and available within

two to three weeks.

The test was developed by Dr.

Danika Bannasch while Bannasch was

conducting post-doctoral research on

canine and equine genetics. The uni-

versity began offering the test to the

public in 1998.

During the last five years, the ge-

netics lab has conducted 4,000 to

5,000 tests, a number that researchers

there say is surprising.

“That is a relatively small number

of horses tested when you compare it

with the large number of horses reg-

istered,” said Dr. Cecilia Penedo, as-

sociate director of the Veterinary

A simple DNA test using

mane or tail hair samples can

help Paint Horse breeders avoid

the heartbreak of producing

lethal white foals.

Genetics Lab. Penedo has worked at

UC Davis as a geneticist since 1982.

“The risk of producing a lethal

white comes when people breed two

horses that carry the overo lethal white

gene,” she explained. “By using the

test, horse owners can determine if

white-spotted horses that are predom-

inantly overo carry the mutation re-

sponsible for lethal white syndrome.”

Although the foal may at first ap-

pear to be normal, it usually begins ex-

hibiting signs of colic within 12 hours

of birth because of a non-functioning

colon, similar to Hirschsprung disease

in humans. Because surgery is not suc-

cessful, OLWS is always fatal, so foals

are often euthanized shortly after

birth.

The affliction occurs more often in

breeds such as Paint and Quarter

Horses that have white in their coats.

It rarely occurs in Thoroughbreds.

The disease is most often associated

with horses that have an overo spot-

ting pattern. Overo includes three pri-

mary patterns—frame overo, sabino

and splashed white—that are geneti-

cally different.

It’s a mystery

The curse of Paint Horse breeders,

lethal white syndrome is one of the

most heartbreaking conditions to af-

flict spotted horses. Also known as

congenital intestinal aganglionosis,

the disease occurs in Paint Horses that

are all, or predominantly all, white.

PAINT HORSE JOURNAL

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MARCH 2004

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145

Frame overo horses are character-

ized by white patches centered in the

neck and body that are framed by col-

ored areas. Research indicates that

frame overo horses are most likely to

produce lethal whites.

The mutation associated with

OLWS also has been found in

horses that have the sabino and

splashed white patterns. The sabino

pattern can range from being mini-

mally expressed in a horse that has

one or more white legs and a blaze

to horses that are almost or com-

pletely white. Most sabinos that are

largely white are quite roaned and

speckled.

In the splashed white pattern, a

horse’s legs and the bottom parts of its

body are usually white, which makes

the horse look like it has been dipped

in white paint. Its head is often white

and its eyes are frequently blue.

However, seeing is not always be-

lieving when it comes to the complex

world of genetics. Although it has

been shown that frame overos can

produce lethal white foals, the disease

can also occur in tobianos and solid-

colored Paint and Quarter Horses

that carry the OLWS gene.

For decades, Paint Horse owners

sought a reliable, scientific way to

identify the deadly characteristic.

When none could be found, many ac-

cepted the risk of getting a lethal

white foal as the cost of breeding

Paints.

Then, in 1997, three independent

research groups made a significant

discovery. Geneticists at the Univer-

sity of Minnesota, the University of

California and at a hospital in Aus-

tralia located the DNA mutation and

gene associated with OLWS. The

Minnesota research was funded by a

grant from the American Paint Horse

Association.

By analyzing the DNA sequence

of the gene in affected foals and

their parents, scientists determined

that lethal white foals have two

copies of the gene responsible for

the disease. As in all genetics, the

offspring gets one copy of a gene

from each parent.

Once the gene was located, the

mystery began to unravel.

The overo pattern includes three primary patterns that are genetically

different. Frame overo horses (top) are the most likely to produce lethal

white foals. Although the mutation linked with OLWS has been found in

sabino (middle) and splashed white (bottom) horses, the risk of their

producing lethal whites is less.

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PAINT HORSE JOURNAL

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MARCH 2004

How it works

Inherited diseases, such as lethal

white syndrome, are caused by mu-

tations or changes in DNA. In

lethal whites, a receptor gene con-

tains a change in the order of the

basic DNA building blocks, which

results in a mutation that affects the

normal development of the foal’s in-

testines.

Animals receive one copy of each

gene, which may be dominant or re-

cessive, from their parents. A horse

that has two copies of the lethal white

gene will be a lethal white.

By knowing a horse’s genetic

makeup and avoiding the crossing of

a stallion and mare that both carry the

lethal white gene, it is possible to pro-

duce foals that are overo, but not

lethal white.

With a Punnett Square, scientists

can predict the possible gene combi-

nations when crossing two horses. If

one uses the letter “O” to symbolize

the overo lethal white gene and “N”

for horses that do not have that gene,

lethal white foals can be symbolized

as “OO” because they have two copies

of the lethal white gene.

The overo parents of the aforemen-

tioned foal would be represented ge-

netically as “NO.” White-spotted or

solid horses that do not have the mu-

tation would be “NN.”

When two overos carrying one copy

of the OLWS gene, or (NO), are bred,

the resulting ratio of offspring as solids,

overos and lethal whites is 1:2:1. This

means that each time two overos who

carry the lethal white gene are crossed,

there is a 25 percent chance of pro-

ducing a lethal white foal.

This percentage may not be readily

apparent in real life because not all

lethal white foals survive birth. Some

are resorbed by the mare during ges-

tation or they are aborted.

When an overo that carries the

lethal white gene (NO) is bred to a

solid-colored horse that does not have

the OLWS gene (NN), there is a 50

percent chance of producing an overo

and a 50 percent chance of getting a

solid. There is no chance of produc-

ing a lethal white foal.

Many people believe they increase

their chance of getting an overo foal

25%

Solid

25%

Overo

25%

Solid

25%

Overo

25%

Lethal

Many people believe they increase their chances of getting an overo foal if

they breed two overos. However, as the Punnett Square on the left shows,

these breeders have a 25 percent chance of getting a lethal white. If an overo

is bred to a solid-colored horse that does not carry the OLWS gene (square at

right) they have a 50 percent chance of getting an overo—the same as when

breeding two overos—but without the risk of producing a lethal white.

25%

Overo

25%

Solid

25%

Overo

if they breed two overos, said Penedo.

But research reveals this is not the

case.

“If they breed an overo to a solid-

colored horse that does not carry the

OLWS gene, their chance of getting

overo offspring is 50 percent, the

same as if they bred two overos,” she

explained. “But they eliminate the 25

percent chance of getting a lethal

white.”

Equine genetics can be very tricky.

You can’t always tell by looking at a

horse if it carries an overo gene. To-

bianos, toveros and solid-colored

horses can all produce lethal white

foals if they have the OLWS gene in

their pedigrees.

That’s where the test comes in.

Using a process called allele spe-

cific polymerase chain reaction

(ASPCR), the test makes it possible

for scientists to look at the region of

the gene responsible for the white

pattern.

“Almost everyone working with

DNA uses this process because it al-

lows us to look at a very specific, very

short piece of DNA that contains the

mutation,” Penedo said.

Although no other mutations asso-

ciated with OLWS have been discov-

ered, there is the rare possibility that

two non-overo horses (NN) could

have a lethal white foal if there is a

mutation at a site different from the

one the test detects.

The test is also useful to breeders

who want to identify pedigree sources

of the overo pattern that may be valu-

able to their breeding programs.

Looks can be deceiving

Just as you cannot tell whether a

horse is at risk for producing lethal

white foals by looking at its coat, a

completely white horse is not always a

lethal white.

Interestingly enough, the white

gene (W) is dominant over all other

coat colors, including gray. This

means that a foal that receives only

one dominant white gene from either

parent will be white. This horse has

white hair, pink skin and dark eyes.

But even though the white gene is

dominant, scientists know that two

dark-colored horses have produced a

white foal. One explanation is that

the white gene may have a high rate

of spontaneous mutation because

foals produced by such crosses have

gone on to breed as if they had a dom-

inant white gene.

Dr. Cecilia Penedo is associate

director of the Veterinary Genetics

Lab at UC Davis.

PAINT HORSE JOURNAL

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MARCH 2004

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147

Whites aren’t always lethal

Peg Fultz couldn’t believe her eyes

as her Paint Horse mare, Ambers Ro-

mance, began to foal during the

morning of May 4, 2001.

Peg and her husband, Daniel, had

bred the bay tobiano mare to their sor-

rel overo stallion, Sonnys Zippin It.

The Fultzes, who own Prism Paints

& Quarter Horses in Bagley, Min-

nesota, have bred and raised horses for

15 years. Originally, the couple

wanted to breed “Sonny” to another

mare who was a frame overo, but they

decided against it after having both

horses tested for Overo Lethal White

Syndrome (OLWS).

“We knew about lethal whites after

being on horse farms and learning

about it from the Paint Horse Journal ,”

Peg noted. “After the test revealed both

horses had one copy of the frame overo

gene, we decided not to breed them.

“We felt it was a matter of respon-

sibility because we knew there was a

25 percent chance of their producing

a lethal white foal and we didn’t want

to create that situation.”

Instead, they bred Sonny to Am-

bers Romance because she is a to-

biano, which doesn’t carry the lethal

white gene unless the horse has overo

in its background.

So, when Peg saw a white coat

emerge as “Amber” began to foal, she

felt uneasy.

“I looked at the baby as it was being

born and saw more and more white

coming out,” she said.

After the foal was finally born, Peg

was devastated. It was a solid white

colt with pink skin and blue eyes.

“He didn’t have a dark spot any-

where,” said Peg. “Believe me, I

looked.

“I almost died because I thought

it was a lethal white. It was heart-

breaking.

“Daniel wouldn’t even look at the

foal. He just knew we were going to

have to put him down.”

The couple knew veterinarians ad-

vised euthanizing lethal white babies

so that they wouldn’t suffer.

Peg immediately logged on to

www.horsesmidwest.com, an equine

chat line created by horse owner Pat

Bores, for advice and comfort from

on-line friends.

“I wanted to talk with them about

what I thought was a horrible situa-

tion,” she recalled.

“Some said to wait and see if the

foal exhibited lethal white symptoms.

They advised me to wait before doing

anything.”

Lethal white foals have non-func-

tioning colons, so they are unable to

pass waste. Because of this, they begin

to show signs of colic within the first

12 hours after they are born.

When Peg finally saw the colt pass

meconium, a newborn’s first excre-

ment, she was elated.

But her joy quickly turned to despair.

“I thought we were out of the

woods,” she said, “but then I found

out we needed for the milk feces to go

through. I didn’t see it from Friday

morning, when the foal was born,

until Sunday night.

“Finally, after the third day, it came.

Boy, was I happy!”

The foal’s registered name is PPQ

Spirit Of Romance, but the Fultzes

call him “Houston.” He remained

healthy, and is a good example of a vi-

able white.

Viable whites are usually a combi-

nation of equine white spotting pat-

terns. Scientists believe such horses

are white because they have two white

spotting patterns that overlap.

One of the genes may carry the overo

lethal white characteristic, but the other

gene carries another white pattern.

After further research into the

pedigree of Houston’s sire and dam,

Peg believes he carries the genes for

four patterns—tobiano, frame overo,

sabino and splashed white. His base

color is red, or sorrel, according to

the results of a red-factor test con-

ducted by the Veterinary Genetics

Lab at the University of California–

Davis.

PPQ Spirit Of Romance (left) is an

example of a viable white horse. His

dam, Ambers Romance (right), is a

bay tobiano. His sire, Sonnys Zippin

It (below), is a sorrel overo.

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PAINT HORSE JOURNAL

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MARCH 2004

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