Breed distribution of the nt230(del4) MDR1 mutation in dogs.

A 4-bp deletion mutation associated with multiple drug sensitivity exists in the canine multidrug resistance (MDR1) gene. This mutation has been detected in more than 10 purebred dog breeds as well as in mixed breed dogs. To evaluate the breed distribution of this mutation in Germany, 7378 dogs were screened, including 6999 purebred and 379 mixed breed dogs. The study included dog breeds that show close genetic relationship or share breeding history with one of the predisposed breeds but in which the occurrence of the MDR1 mutation has not been reported. The breeds comprised Bearded Collies, Anatolian Shepherd Dog, Greyhound, Belgian Tervuren, Kelpie, Borzoi, Australian Cattle Dog and the Irish Wolfhound. The MDR1 mutation was not detected is any of these breeds, although it was found as expected in the Collie, Longhaired Whippet, Shetland Sheepdog, Miniature Australian Shepherd, Australian Shepherd, Wäller, White Swiss Shepherd, Old English Sheepdog and Border Collie with varying allelic frequencies for the mutant MDR1 allele of 59%, 45%, 30%, 24%, 22%, 17%, 14%, 4% and 1%, respectively. Allelic frequencies of 8% and 2% were determined in herding breed mixes and unclassified mixed breeds, respectively. Because of its widespread breed distribution and occurrence in many mixed breed dogs, it is difficult for veterinarians and dog owners to recognise whether MDR1-related drug sensitivity is relevant for an individual animal. This study provides a comprehensive overview of all affected dog breeds and many dog breeds that are probably unaffected on the basis of ∼15,000 worldwide MDR1 genotyping data.

Detection of the nt230[del4] MDR1 mutation in dogs by a fluorogenic 5' nuclease TaqMan allelic discrimination method.

For detection of the nt230[del4] MDR1 mutation, a 4-bp deletion in the canine MDR1 (ABCB1) gene, a TaqMan allelic discrimination assay was designed that allows for MDR1 genotyping without post-PCR processing. Directly after completion of the PCR amplification, the MDR1 genotype can be assigned based on selective fluorescence measurement. For primer selection the locus of a potential 265A>G single nucleotide polymorphism was omitted; this locus is covered by the oligonucleotide PCR primers from most of the hitherto established MDR1 genotyping methods. Dogs homozygous for the nt230[del4] MDR1 mutation show highly increased susceptibility to many drugs commonly used in veterinary medicine including ivermectin. As more than 10 dog breeds are predisposed to this mutation, reliable genotyping methods are necessary to identify affected dogs before drug treatment. This study provides a new allelic discrimination method that detects the MDR1 mutation with high specificity and reliability and is useful for routine diagnostics.