.Org Education Genetic d

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he DNA blueprint a breeder relies on or producing the just right oal is

the same DNA blueprint that deter mines how that oals body will work.

Sometimes the instructions given by the genes can result in a malunction

o important body unctions, such as the immune or nervous systems.

Because these diseases and disorders are inherited, they are known as

being genetic in nature. Sometimes they are le thal, either by natural death or humane

euthanization to end the visible suering o the oal. Other times, the oal is able to

live an extended time, but may ace varying levels o disability during its lie.

Genetic conditions exist among a variety o hor se breeds and even among di-

erent species, including humans. So, these are not something unique to the Arabian

breed. However, there are some conditions that are o special interest to the Arabian

horse owner. Inheritance o most o these is not known, but only hypothesized.

Which genetic diseases and disorders are ound in the Arabian breed

and what are their clinical signs?

Cerebellar Abiotrophy (CA): The Purkinje cells in the brains cerebellum begin

to die, resulting in a severe lack o coordination. The degree o severity can vary, but

most aected individuals are euthanized beore adulthood, due to the hazard they

present to themselves and others.

100 Modernarabian horse August/Sptmb 2007 August/Sptmb 2007 Modernarabian hor

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By AHAs EquinE sTrEss, rEsEArcH And EducATion commiTTEE

This article is the second in an ongoing series ocusing on ArabHal-Arabian and Anglo-Arabian genetics. While we are not geneticin this series, Modern Arabian Horsewill discuss the various colors

coat patterns, provide background and examples o crosses that hresulted or may result in specifc traits, as well as cover diseases

disorders that aect this breed. I theres a specifc topic you woulddiscussed or researched, please email editor@arabianhorses.

An introduction to the genetic diseases and disordersthat aect the Arabian horse (Part two o the genetics series)

Knowledge


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stand and nurse, but in other cases , the clinical signs may

not become noticeable or several weeks. Clinical signs

range rom mild incoordination to the paralysis o both ront

and rear legs. This is the only cer vical spinal cord disorder

seen in horses less than one month o age, and a radiograph

can assist in diagnosing the condition.

Severe Combined Immunodefciency Disorder (SCID):

An aected oal is bor n with a severely weakened immune

system. Because their natural deense system against inec-

tion is not unctioning properly, by the time they are fve

months or so o age, they generally die o an opportunisticinection (such as pneumonia) or they are euthanized.

How are they inherited?

SCID is known to be an autosomal recessive trait and

CA is also thought to be an autosomal recessive trait. While

the genetic nature o LFS and OAAM are not yet ully un-

derstood, some researchers have suggested that these are

also autosomal recessive traits. Autosomal means the trait

is not sex linked, and recessive means that in order or a

oal to be aected, it must have two copies o the mutated

allele, receiving one copy rom each parent.

The mode o inheritance or Juvenile Epilepsy has not

yet been determined. However, there are dierent theories

at present; one suggests that, like epilepsy in humans, multiple

genes may be involved. Another theory suggests that it could

be an incomplete orm o LFS, and a third concern is that

it possibly is an autosomal dominant trait. A dominant

trait means that an aected oal only needs to inherit one

copy o the mutated allele to show clinical signs.

o a dominant trait is Hyperkalemic Periodic P

American Quarter Horses.

How requently do they occur?

Although aected oals are defnitely in the

oals born, these genetic diseases and disorders

enough that all breeders need to be aware o the

it is not possible to test every Arabian horse or e

condition, estimates have to be made based on

is available and the number o aected oals rep

An aected oal is usually bor n without clinical signs.

However, as they begin to grow, the degeneration o the

Purkinje cells begins. Clinical signs include a head tremor

and severe incoordination, combined with an inability to

accurately gauge distance. Additional signs include an exag-

gerated gait and when at rest, a wide-legged stance. Young

horses with CA are also hyper-reactive and somewhat more

prone to rearing than ordinary horses, with the requent

result that they lose their balance and all. Clinical signs may

not appear immediately, but are oten frst noticed at times

when the oal is under close scrutiny, such as weaning.

CA is oten mistakenly diagnosed as Wobblers Syndromeor as head trauma rom an injury. Wobblers Syndrome is

caused by compression o the spinal cord, due to malormation

o the cervical vertebrae during growth, and can be diagnosed

with the assistance o radiographs. Clinical signs can also be

misdiagnosed as head trauma rom an accident, because oals

oten injure themselves by alling over backwards or colliding

with a ence. However, both conditions are quite dierent

rom CA and care should be taken to dierentiate them.

Although clinical signs and case history can lead to a diag-

nosis o CA, at this point in time, the only way to confrm

such a diagnosis is to examine the brain tissue ater euthanasia.

Juvenile Epilepsy: Although not generally atal, it can

be disabling and there has been a suggested genetic link to

Lavender Foal Syndrome. Aected oals are born nor-

mal, but will have periodic epileptic se izures, beginning

anywhere rom 2 days to 6 months ater bir th. Between

seizures, they appear nor mal. Treatment can include the use

o traditional anti-seizure medications, which may reduce

the severity o the clinical signs. Aected individuals usu-

ally outgrow the condition between 12 and 18 months.

Lavender Foal Syndrome (LFS) [also known as Coat

Color Dilution Lethal (CCDL) or Dilute Lethal]: This is a

neurological disorder thought to be caused by a brain lesion.

An aected oal cannot stand at birth and usually has seizures.

LFS oals are requently born with a telltale diluted coat

color that can make the hairs appear to be a dull lavender, a

pinkish-brown or somewhat silvery. In many cases, the oal

was also a product o a difcult delivery. I the coat color is

overlooked or not present, oals may be misdiagnosed as

having neonatal maladjustment syndrome (known as dummy

oals), due to a lack o oxygen rom the dystocia. Foals areusually euthanized within a ew days ater birth.

Occipito-Atlanto-Axial Malormation (OAAM): This is

a condition where the cervical vertebrae use together in the

neck and at the base o the skull, causing compression and

injury to the spinal cord. Aected oals are oten unable to

GeneTiC sTaTus

X = eee allele cae paet (Xx) Aete Paet (x

x = eee allele

cae paet (Xx) 25% aete (xx) 50% aete (x

50% ae (Xx) 50% ae (X

25% -ae (XX) 0% -ae (X

n-ae (lea) Paet (XX) 0% aete (xx) 0% aete (x

50% ae (Xx) 100% ae (X

50% -ae (XX) 0% -ae (X

(Two non-carriers bred together will never produce a carrier or affected foal. Although it is unlikely two affected ho

would be bred together, it is possible, and would produce 100 percent affected foals)

T 1: Proty of G Coto Rtg affct, Crrr & Cr O

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Prior to SCID testing becoming available in 1997, SCID

carrier estimates ranged rom 8 percent to 25 percent. From

the start o testing in 19 97 through May 2, 2007, VetGen,

Inc. has tested about 7,700 horses with 17% testing as SCID

carriers and 0.3 percent testing as aected. Although this is

not a truly random sampling, it does provide a snapshot o

the prevalence o SCID in the Arabian gene pool. It is impor-

tant to note that the number o aected oals in these fgures

is based only on those oals tested by VetGen (it does not

include SCID aected oals who did not have samples s ub-mitted to VetGen or testing).

Based on probability statistics or the behavior o an

autosomal recessive gene, estimates o CA carriers range

rom 17 percent to 35 percent, with 25 percent oten be-

ing used as an average. Because the condition is under-

reported, researchers can only state this disease aects a

signifcant number o horse s every year.

The number o aected oals born with

recessive genetic conditions is directly tied

to the requency o two carriers being bred

together (see table 1). An aected oal can-

not be produced unless two carriers are bred

to one another. However, a carrier bred to

a non-carrier results in a 50/50 chance the

ensuing oal will also be a carrier. For every

two carriers bred together, there is a 25%

chance an aected oal will result rom that

mating. Because some horses with CA can

be bred, it is important to remember that

all oals rom a CA aected parent will be

carriers, even i bred to a CA clear Arabian

or a horse o another breed.

Does linebreeding or inbreeding cause these

diseases?

No. However, the more the gene pool is reduced by

closely breeding related horses, and i carriers are present,

the requency o the mutated allele(s) has the potential to

in-crease in the population.

Is there any bloodline o Arabian horse more or

less likely to have genetic conditions?

No, all lines in the Arabian breed have the potential to

carry genetic conditions. For example, SCID and CA have

appeared in virtually all modern bloodline groups and ap-

pear to be distr ibuted throughout the breeding population.

In addition, while LFS is oten associated with horses o

Straight Egyptian or heavy Egyptian breeding, it has been

identifed in other breeding groups.

Doesnt the SCID test fnd all genetic problems?

No, although it was a wonderul breakthrough, SCID test-

ing cannot determine carrier status o other conditions (just

as parentage testing with DNA cannot be used or genetic

disease testing). Each condition requires its own special test.

Did one horse or bloodline cause these diseases?

Arent these diseases a sign o impure breeding?

No and No. Cellular mutations are caused every time a cell

divides; usually they have little to no eect. However, some-

times these mutations do end up alter ing a cells unction.In addition, while some historical animals are very likely

to have been carriers (based on pedigree analysis o get or

grandget who produced aected oals), there is anecdotal

evidence that at least some o these conditions appeared even

in desert bred Arabians. To quote the late Dr. Ann Bowling:

Deleterious mutations that occur in purebred breeds are

usually chance hitch-hikers in highly successul bree ding

lines, otherwise, the homozygous genotypes that produce the

problem conditions would be so rarely encountered as to be

overlooked or written-o as problems with unknown causes.

Cant we eliminate genetic diseases by not breed-

ing known carriers?

Without a test, it is impossible to identiy all carriers. Just

because a horse has so ar never produced an aected oal

does not mean it is clear. Because stallions can sire many

ospring, they are more likely to eventually be revealed as a

carrier. Mares, however, may be unrecognized carriers. Even

i bred to a car rier stallion, statistical probability may mean

that they never produce an ae cted oal. Thus, a recessive

gene can be passed on or generations without an aected

oal being born.

Further, by removing all known carriers rom the

breeding population, the already limited Arabian gene

pool would become even more limited and the breed

could lose some highly valued bloodlines. In addition, a

less-diverse breeding population may actually allow other

genetic conditions to become more widely distributed.

The success o SCID testing indicates that i known carri-

ers are bred, with careul, selective breeding and testing o

ospring, even carrier lines can be cleared o

The SCID test allows people to avoid ever b

aected animal, and allows breeders to make an

choice to breed or not breed a carrier, as they m

However, or the remaining conditions, until th

DNA test, there is no way to know which hors

gene, short o producing an aected oal. Likew

when two carriers are bred, there is an equal sta

probability that their ospring will be clear or a

guilt by association may unnecessarily taint the

o horses that actually do not carry the gene at

This is why it is so critical or breeders to su

ability o modern science to locate the genes th

these conditions. Developing genetic tests is a m

The role o the Equine Stress, Research and Educati

tee is to discuss the types o stress-related horse abuse

today and make recommendations on how to elimina

stress; to oster and encourage educational programs, s

breed improvement and animal husbandry; and to st

make recommendations on related topics o drugs and

stress, research contributions and other subjects. Speci

Lisa Goodwin-Campiglio, Beth Minnich and Brend

helping to put together this article.

Currently, SCID is the only condition that has a test avail-

able. It can be ordered through FOAL or $99/test:

Arabian F.O.A.L. Association

Marguerite Illing, Treasurer, 853 Cooley Road, Parksville,

NY 12768-5336

http://www.oal.org/user/orderkit.pd

UC Davis in Caliornia is doing research on CA and LFS.

Interested persons in the United States and Canada should

contact Dr. Cecelia Penedo at:Veterinary Genetics Laboratory

One Shields Avenue, Davis, CA 95616-8744

Phone (530) 752-2211, Fax (530) 752-3556

http://www.vgl.ucdavis.edu/research/equine/CA.html

In addition, Dr. Monica Aleman at UC Davis is research-

ing juvenile epilepsy. For more inormation, contact:

[email protected], (530) 752-1170 or (530) 752-

7267, Neuromuscular Disease Laboratory, UC Davis

Researchers at the University o Berne in Switzerland

are also investigating CA and breeders in Europe, the

Middle East and Australia who can provide DNA samples

are urgently needed. They will be working in a loose col-

laboration with Dr. Penedo at UC Davis.

http://www.vetsuisse.unibe.ch/genetic/content/e

e2734/index_eng.html

For additional inormation, contact the molecula

cist; Pro. Dr. Tosso Leeb, Institute o Genetics, Univ

Berne, Bremgartemstr. 109a, P.O. Box 8466, 300

Switzerland, e-mail: [email protected]

And/or: Vincent Gerber, PhD. DACVIM, DECE

Head o Equ ine Internal Medicine, Vetsuisse-Fakulsity o Berne, Langgass-strasse 124, 3012 Berne,

land, e-mail: [email protected],ch

It is vitally important or breeders and owners to

stand that without samples, it is virtually impossible

researchers to advance their work. For example, th

need 10 brain specimens rom CA aected horses

minimum o 20 blood samples rom related amily in order to give their research a solid base to work

Even though the idea o submitting blood and b

samples can be uncomortable, and certainly a very

decision or a breeder or owner; it is a necessity, s

test can be developed. Once a test is developed, b

have the ability to never produce an aected oal

That is the ultimate goal.

aRe TesTs available TO deTeRmine CaRRieRs?

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