Multidrug Resistance 1
Affected Genes: ABCB1
Inheritance: Autosomal Incomplete Dominant
Variant(canFam6):
chr14:13298171-13298174: 4 bp deletion ATCT
Breed: Aussiedoodle
Australian Cattle Dog
Australian Koolie
Australian Labradoodle
Australian Shepherd
Australian Stumpy Tail Cattle Dog
Australian Working Kelpie
Bernedoodle
Border Collie
Bordoodle
Carolina Dog
Cavapoo
Cavapoochon
Chinook
Cockapoo
Collie
Danish-Swedish Farmdog
Danoodle
English Shepherd
German Shepherd Dog
Goldendoodle
Irishdoodle
Koolie
Labradoodle
Longhaired Whippet
Maltipoo
McNab Shepherd
Miniature American Shepherd
Miniature Australian Cattle Dog
Miniature Australian Shepherd
Miniature Poodle
Newfypoo
Old English Sheepdog
Old-Time Scotch Collie
Poodle
Rough Collie
Schnoodle
Scottish Collie
Sheepadoodle
Shetland Sheepdog
Shiloh Shepherd
Silken Windhound
Smooth Collie
Standard Poodle
Toy Australian Shepherd
Toy Poodle
Waller
White Shepherd Dog
Yorkiepoo
General Information: Multidrug Resistance 1 (MDR1) is an inherited condition affecting various dog breeds, particularly herding breeds like Collies, Australian Shepherds, and German Shepherds. This condition is caused by a mutation in the ABCB1 gene, which disrupts the function of P-glycoprotein, a crucial protein for removing certain drugs and toxins from the body. Dogs with MDR1 may exhibit severe reactions to specific medications, including common drugs like ivermectin, loperamide, and vincristine. Clinical signs of adverse drug reactions can include vomiting, weakness, uncoordinated movement, tremors, seizures, blindness, and even death. These symptoms occur because the defective P-glycoprotein allows drugs to accumulate in the brain and other organs. To prevent these potentially life-threatening reactions, it is essential for veterinarians to know if a dog has the MDR1 mutation before prescribing medications.
How to Read Your Dog's Test Results for this Genetic Variant:
Two Variants Detected: Dog Likely Affected
One Variant Detected: Dog Possibly Affected
No Variants Detected: No Effect
Gene / Testing Information: Genetic testing for the ABCB1 gene mutation can reliably determine if a dog is a carrier of MDR1. This condition is inherited in an autosomal incomplete dominant manner, meaning that dogs with one or two copies of the mutated gene are at risk of drug sensitivities. Even carriers (dogs with one copy of the mutation) can experience adverse drug reactions, though these reactions are typically more severe in dogs with two copies of the mutation. When breeding, it is crucial to avoid mating two carriers, as this increases the risk of producing affected puppies. Each pup from such a pairing has a 25% chance of inheriting two copies of the mutation and a 50% chance of inheriting one copy. Reliable genetic testing is vital for making informed breeding decisions to prevent passing on the MDR1 mutation and to manage dogs at risk for drug sensitivities appropriately. Dogs without the mutation have no increased risk of producing affected pups when bred to other clear dogs.
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 25(3):484-489.
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 20(2):111-114.
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 11(8):e0161005.
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 106:89-92.
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 30(5):482-485.
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 189(1):67-71.
Mealey KL, Bentjen SA, Gay JM, Cantor GH. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics. 2001 11(8):727-733.
Mealey KL, Meurs KM. Breed distribution of the ABCB1-1delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping. J Am Vet Med Assoc. 2008 233(6):921-924.
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 24(1):127-134.
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 USA. 2004 101(32):11725-11730.
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 17(3):354-356.