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Narcolepsy (NARC) Test:

For: Dachshunds, Doberman Pinschers, and Labrador Retrievers

Please note cheek swabs are not accepted for this test.

Photo: Dachshund Photo: Doberman Photo: Labrador

The OptiGen Narcolepsy – NARC - test is a DNA-based test that provides, for the first time, a method to unequivocally identify narcolepsy in several breeds – Doberman Pinschers, Labrador retrievers and Dachshunds. This test allows you to control the narcolepsy gene frequency in your breed so as to prevent producing puppies affected with the disease.

An article by Mary M. Woodsen tells the story of how this test was developed. The article follows below, after the information on testing.

Reliable identification of dogs that do not carry disease genes is the key to controlling autosomal recessive diseases. The OptiGen NARC test enables 100% accurate identification of these dogs. Called "genetically clear," "noncarriers" or, more formally, "homozygous normals," such dogs can pass only the normal gene on to all their pups-which means that none of their pups can ever be affected with narcolepsy. These "clear" dogs can be bred to any mate, even to a narcolepsy-affected dog which may be a desirable breeding prospect for other reasons.

Homozygous means both copies of the gene in your dog are the SAME - both normal or both NARC. A carrier has one normal and one NARC gene.

Because the OptiGen NARC test is a mutation-based gene test, it accurately and specifically identifies normal dogs, carriers (heterozygous dogs) and affecteds. Possible test results are listed in the table below.

Possible results using the OptiGen NARC test
N= Normal (Clear) Homozygous for normal gene, so will never develop the disease
C= Carrier Carries one disease gene, but will never develop the disease
A= Affected Homozygous for disease gene and will develop the disease
 This is the result that will be reported by the OptiGen Narcolepsy test.

The following table highlights all the desirable breedings that will not produce affected pups. These breedings include at least one parent proven "normal" by the OptiGen NARC test. All other breedings are at risk of producing narcolepsy-affected pups. However, all dogs can be bred safely. It isn't necessary-or even desirable-to remove any dog from the breeding population. But when choosing pups to retain as potential breeding stock, it is important to select for dogs proven "normal" by the OptiGen NARC test-and select, when possible, against dogs proven to be carriers. Pups can be tested to distinguish carriers from normals as soon as they are old enough to have a small blood sample collected.

Expected results of breeding strategies using OptiGen mutation tests for inherited recessive diseases
Parent 1
Genotype
Parent 2     Genotype
Normal Carrier Affected
Normal All = Normal 1/2 = Normal
1/2 = Carriers
All = Carriers
Carrier 1/2 = Normal
1/2 = Carriers
1/4 = Normal
1/2 = Carriers
1/4 = Affected
1/2 = Carriers
1/2 = Affected
Affected All = Carriers 1/2 = Carriers
1/2 = Affected
All = Affected

How you can participate...
The NARC Test is done on a small sample of blood obtained by your veterinarian. This allows the lowest risk of contamination of the sample and added assurance of a match of the sample with the identified dog.

Read and print the instructions on the Ship Sample page. Then fill out the Test Request Form. On-line submission of the Test Request Form lets you be sure accurate information and correct spellings are put in the database. And, when you've completed one Form, a second Test Request Form for another dog or for a litter is easy and saves you time.

A patent application for the technology underlying this test has been filed and OptiGen has obtained an exclusive license for it from Stanford University.

 

Dog Tired?


This article was first published in Dog News, The Digest of American Dogs, volume 16, issue 25 on June 23, 2000 and is reprinted here with the permission of Mary M. Woodsen & Dog News.

 

When Emmanuel Mignot M.D, Ph.D., a specialist in sleep disorders at Stanford University’s School of Medicine, decided to unravel the cause of a condition that overwhelms 1 in every 2000 people with daytime “sleep attacks,” he turned to man’s best friend—and in particular to Doberman Pinschers, Labrador Retrievers, and Dachshunds. These dogs, too, can suffer from narcolepsy. Mignot knew that once he found the cause of narcolepsy in dogs, he’d be that much closer to figuring out how the disease works in humans—and how to treat it.

In dogs, narcolepsy is frequently inherited. The mutated gene that causes it is recessive, which means that if a dam and sire are both carriers, one-quarter of their pups will have the disease and one half will be carriers. Affected dogs are often described as falling fast asleep right in their tracks—but that’s not quite the case. Indeed, they suddenly lose control of their hind legs, or even collapse in complete, limb-numbing paralysis—yet they are entirely aware of their surroundings and can track things with their eyes. Attacks last a few seconds, or a minute or two, tops; then the dog is up again and moving, with no residual grogginess, no indication that things were ever amiss.

In fact, an attack of narcolepsy mirrors what’s called REM sleep. REM stands for “rapid eye movement.” It’s the kind of sleep that we—dogs and people both—go into when we dream: and we all dream, whether we remember it or not. Our eyes move rapidly as we dream, but our muscles become atonic: that is; they are completely slack; they have no tone. Though we may twitch or jerk, the muscles themselves are incapable of controlled, coordinated movement. If something awakens us in mid-dream, we may feel paralyzed.

Normally when we sleep, we start out gently in “non-REM” sleep: our muscles are partially relaxed, our brain waves are modulated. As the night wears on we cycle back and forth between REM and non-REM sleep, and if we have the requisite amount and proportion of both we awake feeling refreshed.

But people—and dogs—with narcolepsy are short-changed on REM sleep. So all day long, their bodies try to make up for it. That’s why attacks frequently consist of cataplexy: the paralyzing sensation of partial or full atonia (no muscle tone, as in REM sleep), and sufferers slump suddenly to the ground, unable to communicate while yet completely conscious. (Narcolepsy is entirely different from such seizure-based diseases as epilepsy, where muscles become tight, even rigid, and consciousness is blurred.)

Let sleeping dogs lie
Occasionally a dog may slip from paralysis into sleep, just as human narcoleptics tend to do. Narcoleptic dogs are sleepier than normal dogs during the day and have a tendency to doze more frequently than normal dogs. But dogs are notable nappers, spending about 30% of their daytime hours snoozing. It’s not always easy to tell when they’re dozing and when the narcolepsy has kicked in. Then again, it may be that people with narcolepsy simply amass a larger REM-sleep deficit each night than dogs do, and do actually more often fall asleep as a result. In any case, the sleepiness is usually less a problem than are the muscle paralysis (cataplexy) attacks.

Narcolepsy generally shows up in puppyhood, as early as four weeks of age and certainly by the time a dog is six months old. Frequency is tremendously variable. Attacks can happen once a year—or a hundred times a day. For severely affected dogs, the attacks are predictable, but for moderately affected dogs—you just never know. It’s even possible that some mildly-affected dogs are never diagnosed, because attacks are so infrequent and short-lived that no one ever observes them. Usually narcolepsy is most severe during a dog’s early years. But though it often mellows out with age, it never really goes away.

To date, the treatments for narcolepsy in dogs parallel those for humans. Veterinarians may prescribe antidepressants, stimulants, or extracts of yohimbe, an African botanical also used as an aphrodisiac. But regardless of the source, treatments generally make dogs hyper, and most owners prefer—as it were—to let sleeping dogs lie.

Give a dog a bone
Intriguingly, it’s pleasurable stimuli that bring on narcolepsy episodes. In dogs, chow time is prime time for an attack. Give an affected dog a bone and within seconds it’s on the floor. In fact, any exciting, happy time can bring on an attack—the owner’s return after a long day away; play time with other dogs: any new or stimulating experience.

Though an episode may bring an affected dog crashing to earth in mid-bound, there’s no real health risk associated with narcolepsy. It’s not a prelude to other diseases, nor is it linked to temperament or longevity. About the only danger in narcolepsy would be if the dog is in the wrong place at the wrong time doing the wrong thing—say, chasing a ball into a busy street. Which of course no conscientious owner would allow in the first place.

Variable as narcolepsy is in dogs, it generally boils down to one recessive, malfunctioning gene. Actually, make that two, because in order to be affected with hereditary narcolepsy, a dog has to have two defective copies of this gene—one from each parent. In other words, each parent has to be either a carrier or affected. But until Mignot found the gene (known as hypocretin receptor 2, or Hcrtr2), there was no way to tell which dogs were carriers.

REM sleep, exuberance, delight in tasty food, muscle tone—these are all states that begin in the brain. Within the brain, various constellations of neurons—kazillions of neurons!—are continually zinging us messages that say—according to the time of day, the needs of our bodies, and the things that are going on around us—“enjoy! sleep! play! eat!” But these neurons only fire when provoked by molecules of message-bearing neurotransmitters. And each of these transmitter molecules can only convey its message if it can fit properly into specific transmitter receptor molecules that sit on certain types of neurons.

The Hcrtr2 gene produces a receptor in the brain that fires off signals every time that molecules of the neurotransmitter hypocretin click into it. This receptor links to neurons that control emotions, REM sleep and muscle tone. In narcoleptic dogs Hcrtr2 is defective and the receptor is skewed.

Of course, plenty of other genes affect pleasure, exuberance, REM sleep, and muscle tone—that’s why there’s such variation in the frequency of episodes. But affected dogs often collapse at the first charge of excitement.

The test of time
What made the gene defective, and how does it actually cause narcolepsy? Somewhere back in Doberman history, a scrap of oddball DNA got plugged into Hcrtr2. In Labs, a scrap of DNA in that same gene got punched out. For both breeds, the effect is the same—the skewed gene makes a malformed receptor that won’t fire when certain neurotransmitters press the trigger. Now that this defective gene can be identified, a reliable test for narcolepsy is available that identifies carriers and affecteds with certainty in Labrador Retrievers and Dobermans.

Tests for Dachshunds (and soon, for Poodles and Beagles) are likewise available. But the cause of disease in these breeds is sometimes in question. Often it’s hereditary, and if so, the gene at fault is that same Hcrtr2; the test will disclose carrier and affected status. But sometimes narcolepsy has other, less well understood causes—most likely environmental in origin. Narcolepsy in dogs and people that isn’t clearly linked to a gene is called sporadic narcolepsy. (Most human narcoleptics have the sporadic form.)

The narcolepsy test is simple and straightforward; it requires but a small sample of blood. This test is among a growing number of tests for various canine diseases now offered to savvy breeders who use them, not to eliminate otherwise excellent carriers and affecteds, thus narrowing their breed’s gene pool, but to include all worthy dogs in “safe breeding” programs. For breeders who know or suspect they have narcolepsy in their kennels, this test could save their lines so they don’t have to start over.

It’s unclear what percentage of dogs is affected by narcolepsy. That will be the “test of time,” learned as dogs are tested. Just now it seems that the disease isn’t very common. But it’s important to have tests available for diseases that, while not frequent now, could become more frequent in years to come. Breeders may have good reasons in choosing and breeding affected (or carrier) sires and dams. They may need to use them to point up other favored traits—or to avoid yet other hereditary diseases. When that happens, this test is there for them.

Stanford University has chosen OptiGen to be the exclusive provider of this test.

 


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Tel: 607 257 0301 · Fax: 607 257 0353 · email: genetest@optigen.com or optigen@clarityconnect.com
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