Genetic Testing & MDR1

There are several factors that go into responsible and ethical breeding. It’s one in which we don’t take lightly here at Coyote Creek. There needs to be a purpose, a demand and quality stock.

We first and foremost are breeding to the standard, which for each toy, miniature and standard size Aussies, is the same. Our dogs are NOT crossed with other breeds to get a smaller size, they have been bred down over generations to smaller stature. They are all the same dog essentially but in different size packages. There are different lines, some higher or lower in herd drive and energy levels but the body is to fit the standard regardless. All of our dogs are registered via the AMERICAN STOCK DOG REGISTRY.

 

Secondly we consider temperament is another very important aspect. A beautiful dog isn’t much good to a family if it is nasty by nature. Our dogs are derived from gentle natured lines, social, friendly and out-going. We put a vast amount of energy into socialization and care before your puppy gets to you to make sure we’ve done all that we can to ensure a life long companion who is ready to fit into your family. We follow, to the best of our ability and practice, the PUPPY CULTURE PROGRAM. We encourage our families to research this method and continue on with it when your puppies comes home with you. Nature as well as nurture will always be important.

To complete the total package of the perfect Australian Shepherd companion is health. It is no less important than confirmation and companionship, intact it is necessary for the other two things to properly exist. A beautiful bodied, friendly Aussie doesn’t have much if he doesn’t have health. New owners don’t need to be strapped with vet bills either, acquiring an Aussie should be a positive experience all the way around. To insure sound health in our dogs and pups we trust PAW PRINTS GENETICS with the care of providing us accurate results regarding our dog’s genetic health. You can learn about every genetic trait your pup’s parents have been tested for. All our dogs are tested prior to breeding to ensure nothing has been overlooked.

Included below are links to each of the genetic tests in the <standard, Mini & Toy? Australian Shepherd Panels. By testing each of our breeders we can determine anything that your pup may be a carrier for. We have no P/P (postive) genetically testing dogs.

 

 

 

 

 

MDR1- WHAT YOU NEED TO KNOW.

Here at Coyote Creek, we treat all our dogs as if they are positive for MDR1, even though none of them are. While we do have 2 carriers, who could be mildly affected by the disease, we’ve removed all associated risks by simply not giving them the products that could harm them.

It is imperative that Australian Shepherd owners and enthusiasts learn the facts on MDR1. Then, and only then, can you make informed decisions. Included in this article is a PRINTABLE LIST that you can give to your Licensed Veterinarian as well. Believe it or not, not every Vet is current on MDR1 facts.

Below you will find the MDR1 excerpt directly from PAW PRINTS;

 

Multidrug Resistance 1

 

Other Names: Ivermectin sensitivity, MDR1 gene defect, Multidrug sensitivity, MDR1

Affected Genes: ABCB1

Inheritance: Autosomal Incomplete Dominant

Mutation: Deletion

Breed(s): Aussiedoodle, Australian Koolie, Australian Shepherd, Border Collie, Bordoodle, Chinook, Collie, Danish-Swedish Farmdog, English Shepherd, German Coolie, German Shepherd Dog, Koolie, Longhaired Whippet, McNab Shepherd, Miniature American Shepherd, Miniature Australian Shepherd, Old English Sheepdog, Old Scotch Collie, Rough Collie, Scottish Collie, Sheepadoodle, Shetland Sheepdog, Shiloh Shepherd, Silken Windhound, Smooth Collie, Toy Australian Shepherd, Waller, White Shepherd Dog

 

 

Common Symptoms

 

Multidrug resistance 1, also called MDR1, is an inherited condition affecting several breeds of dogs, especially herding dogs or descendants of herding breeds. The Mutation in the ABCB1 gene associated with MDR1 causes dysfunction of P-glycoprotein, which is responsible for removing certain drugs and toxins from the body. Clinical signs are most commonly associated with distribution of the drug in the central nervous system. MDR1 is inherited in an autosomal incomplete dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing adverse reactions to certain medications. Though adverse reactions to certain drugs are most commonly seen in dogs having two copies of the mutated gene, Carrier dogs can also experience drug sensitivities and dosages need to be adjusted accordingly. Thus, dogs that have one or two copies of the mutation are considered at-risk for adverse drug reactions. If an at-risk dog is treated with one of several common drugs (see below*), they are at risk of developing neurologic symptoms that could range from tremors, excess salivation, anorexia, and blindness to coma and even death. Because of the defective ability to metabolize specific drugs, these drugs can be lethal even at low doses. The MDR1 mutation does not cause adverse effects in dogs unless the dog is exposed to these drugs. Therefore, veterinarians should be notified when a dog is at risk for multidrug resistance 1 prior to administration of any medications.

 

*Drugs known to cause neurological signs related to the MDR1 mutation:

 

Acepromazine, butorphanol, doxorubicin, emodepside, erythromycin, ivermectin, loperamide, milbemycin, moxidectin, rifampin, selamectin, vinblastine and vincristine.

 

In addition to this list, there are many other drugs known to be removed from the central nervous system via the P-glycoprotein mechanism in humans. However, reports of neurological dysfunction related to drugs other than those listed here are scarce in dogs. Please consult your veterinarian prior to giving drugs to known multidrug resistance carriers, affected dogs, or untested dogs of breeds commonly affected with this condition.

 

Testing Tips

Genetic testing of the ABCB1 gene will reliably determine whether a dog is a genetic Carrier of multidrug resistance 1. Multidrug resistance 1 is inherited in an autosomal incomplete dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing the disease. Though adverse reactions to certain drugs are most commonly seen in dogs having two copies of the mutated gene, carrier dogs can also experience drug sensitivities and dosages need to be adjusted accordingly. Thus, dogs that have one or two mutant copies of the gene are considered at-risk for adverse drug reactions. When carriers of this Mutation are bred with another dog that also is a carrier of the same mutation, there is risk of having affected pups. For each pup that is born to this pairing, there is a 25% chance that the puppy will inherit two copies of the mutation and a 50% chance that the puppy will inherit one copy of the mutation and, in either case, may be susceptible to having adverse drug reactions. Reliable genetic testing is important for determining breeding practices. Because symptoms do not appear unless dogs are exposed to certain drugs, genetic testing should be performed before breeding. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups when bred to a dog that is also clear for this mutation.

 

There may be other causes of this condition in dogs and a normal result does not exclude a different mutation in this gene or any other gene that may result in a similar genetic disease or trait.

 

References

Alves L, Hulsmeyer V, Jaggy A, Fischer A, Leeb T, Drogemuller M. Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic border collies. J Vet Intern Med. 2011 May-Jun;25(3):484-9. [PubMed: 21488961]

Barbet JL, Snook T, Gay JM, Mealey KL. ABCB1-1 Delta (MDR1-1 Delta) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis. Vet Dermatol. 2009 Apr;20(2):111-4. [PubMed: 19171022]

Donner J, Kaukonen M, Anderson H, Moller F, Kyostila K, Sankari S, Hytonen M, Giger U, Lohi H. Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders. PLoS One. 2016 Aug 15;11(8):e0161005. [PubMed: 27525650]

Firdova Z, Turnova E, Bielikova M, Turna J, Dudas A. The prevalence of ABCB1:c.227_230delATAG mutation in affected dog breeds from European countries. Res Vet Sci. 2016 Jun;106:89-92. [PubMed: 27234542]

Geyer J, Klintzsch S, Meerkamp K, Wohlke A, Distl O, Moritz A, Petzinger E. Detection of the nt230(del4) MDR1 mutation in White Swiss Shepherd dogs: case reports of doramectin toxicosis, breed predisposition, and microsatellite analysis. J Vet Pharmcol Ther. 2007 Oct;30(5):482-485. [PubMed: 17803743]

Gramer I, Leidolf R, Doring B, Klintzsch S, Kramer E, Yalcin E, Petzinger E, Geyer J. Breed distribution of the nt230(del4) MDR1 mutation in dogs. Vet J. 2011 Jul;189(1):67-71. [PubMed: 20655253]

Mealey KL, Bentjen SA, Gay JM, Cantor GH. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics. 2001 Nov; 11(8):727-33. [PubMed: 11692082]

Mealey KL, Meurs KM. Breed distribution of the ABCB1-1delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping. J Am Vet Med Assoc. 2008 Sep 15;233(6):921-4. [PubMed: 18795852]

Mizukami K, Chang H, Yabuki A, Kawamichi T, Hossain MA, Rahman MM, Uddin MM, Yamato O. Rapid genotyping assays for the 4-base pair deletion of canine MDR1/ABCB1 gene and low frequency of the mutant allele in border collie dogs. J Vet Diagn Invest. 2012 Jan;24(1):127-34. [PubMed: 22362942]

Neff MW, Robertson KR, Wong AK, Safra N, Broman KW, Slatkin M, Mealey KL, Pedersen NC. Breed distribution and history of canine mdr1-1delta, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11725-30. [PubMed: 15289602]

Nelson OL, Carsten E, Bentjen SA, Mealey KL. Ivermectin toxicity in an Australian shepherd dog with the MDR1 mutation associated with ivermectin sensitivity in collies. J Vet Intern Med. 2003 May-Jun;17(3):354-6. [PubMed: 12774979]

 

More on MDR1

 

Here is the MDR1 excerpt from ANIMAL GENETICS;

 

 

Multi-Drug Resistance Gene (MDR1)

 

 

Description:

 

Multi-Drug Resistance Gene (MDR) codes for a protein that is responsible for protecting the brain by transporting potentially harmful chemicals away. In certain breeds, a mutation occurs in the MDR1 gene that causes sensitivity to Ivermectin, Loperamide, and a number of other common drugs. Dogs with this mutation have a defect in the P-glycoprotein that is normally responsible for transporting certain drugs out of the brain. The defective protein inhibits the dog’s ability to remove certain drugs from the brain, leading to a buildup of these toxins. As a result of the accumulation of toxins, the dog can show neurological symptoms, such as seizures, ataxia, or even death.

 

Dogs that are homozygous for the MDR1 gene (meaning that they have two copies of the mutation) will display a sensitivity to Ivermectin and other similiar drugs. These dogs will also always pass one copy of the mutation to all potential offspring. Dogs that are heterozygous (meaning they have only one copy of the mutation) can still react to these drugs at higher doses. Also, there is a 50% chance that a dog with one copy of the mutation will pass it on to any offspring.

 

There are many different types of drugs that have been reported to cause problems. The following is a list of some of the drugs:

 

Ivermectin (found in heartworm medications)

Loperamide (Imodium over the counter antidiarrheal agent)

Doxorubicin

Vincristine

Vinblastine (anticancer agents)

Cyclosporin (immunosuppressive agent)

Digoxin (heart drug)

Acepromazine (tranquiliser)

Butorphanol (“Bute” pain control)

The following drugs may also cause problems:

Ondansetron

Domperidone

Paclitaxel

Mitoxantrone

Etoposide

Rifampicin

Quinidine

Morphine

 

Acceptable Sample Types:

Animal Genetics accepts buccal swab, blood, and dewclaw samples for testing. Complimentary sample collection kits are available and can be ordered at test now.

T

his Test Is Relevant For the Following Breeds:

Australian Shepherd, Border collie, Collie, English Shepherd, Longhaired Whippet, McNab Shepherd (McNab Border Collie), Old English Sheepdog, Shetland Sheepdog (Sheltie), Silken Windhound, Rough Collie, Smooth Collie, German Shepherd, Bobtail, American White Shepherd

 

Results:

 

Animal Genetics offers DNA testing for multi-drug resistance gene (MDR1). The genetic test verifies the presence of the recessive MDR1 gene and presents results as one of the following:

 

MDR/MDR- Affected – The dog carries two copies of the mutant gene and is homozygous for the MDR1 mutation. The dog will react to Ivermectin, or other listed drugs, and will always pass a copy of the mutated gene to its offspring.

MDR/n- Carrier – Both the normal and mutant copies of the gene detected. Dog is a carrier for the MDR1 mutation, and can pass on a copy of the defective gene to its offspring 50% 0f the time.

n/n- Clear – Dog tested negative for the MDR gene mutation, and will not pass on the defective gene to its offspring.

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