Breed is associated with the ABCB1‐1Δ mutation in Australian dogs

Abstract

Objective The ABCB1 gene encodes P‐glycoprotein (P‐gp), a cellular membrane pump. One functional mutation that leads to expression of a less functional form of P‐gp, ABCB1‐1Δ, has been described in dogs. Individuals with this mutation can have severe adverse reactions to common veterinary pharmaceuticals that are known substrates of this pump. We investigated the detection of this mutation in samples submitted to two Australian diagnostic laboratories. Methods A total of 4842 dogs across 27 breeds were tested for the ABCB1‐1Δ mutation from buccal swabs or EDTA blood using standard PCR, multiplex PCR, or genotyping chip. Statistical analysis was applied to determine the proportions and odds ratios of the ABCB1‐1Δ mutation in herding breeds compared with non‐herding breeds. Results The ABCB1‐1Δ mutation was detected in nine breeds. The most commonly affected breeds were collies, Australian shepherds, white Swiss shepherds, and Shetland sheepdogs. Of 32 dogs in 18 non‐herding breeds tested, one cocker spaniel and one labradoodle were positive for the mutation, both heterozygous. Conclusion The most frequently affected breeds for ABCB1‐1Δ mutation are the collie, Australian shepherd, white Swiss shepherd and Shetland sheepdog. As the mutation is associated with an increased incidence of adverse reactions to commonly used pharmaceuticals, veterinarians need to be aware of the breeds at most risk of carrying this mutation and consider testing these individuals prior to administering these medications.

Single-cell molecular profiling of all three components of the HPA axis reveals adrenal ABCB1 as a regulator of stress adaptation

“…A polymorphism in the ABCB1 gene affects intact HPA axis response in depressed human patients Individuals who lack ABCB1, as it occurs in some breeds of dogs with the ABCB1-1 mutation (45), have severe adverse reactions to common medications that act as substrates of this transporter, such as immunosuppressants and steroid hormones (46). Previous studies have shown that dogs and rodents lacking a functional Abcb1/ ABCB1 gene have a blunted HPA axis response compared to wild-type animals (41,47).…”

The prevalence of the ABCB1-1Δ variant in a clinical veterinary setting: The risk of not genotyping

“…While reported first in the collie, multidrug sensitivity caused by the ABCB1-1Δ variant has been described in a wide variety of dog breeds: collies and collie-like dogs but also seemingly unrelated breeds [ 15 , 19 , 20 , 26 ] and cross-bred dogs [ 21 , 22 ]. Interestingly, the presence of this variant could be traced back to the collie lineage for the longhaired whippet, silken windhound [ 15 ], and white Swiss shepherd dog [ 18 ], who all share the ABCB1-1Δ variant identical by descent (IBD) with herding breeds from the collie lineage.…”

“…This link to a white coat and the fact that the white Swiss shepherd (for which IBD was established [ 18 ]) originated from the white German shepherd dog indicates the variant has the same origin as all other breeds [ 24 ]. However, to the authors’ knowledge, there is no known IBD link between the collie lineage and the cocker spaniel, labradoodle, and several crossbreeds in which the ABCB1-1Δ variant has also been reported [ 20 – 22 ]. Furthermore, independent laboratories have reported the presence of the variant in more breeds seemingly unrelated to collies, like the black mouth cur, Carolina dog, and chinook [ 33 ].…”

“…Furthermore, independent laboratories have reported the presence of the variant in more breeds seemingly unrelated to collies, like the black mouth cur, Carolina dog, and chinook [ 33 ]. It should be noted that the ABCB1-1Δ variant has only been reported in one labradoodle and one cocker spaniel [ 20 ] and while some laboratories report prevalences, they do not always mention the number of dogs tested [ 33 ]. As large-scale ABCB1-1Δ related studies on these “collie-unrelated” breeds are lacking, variant allele frequencies remain unknown.…”

“…The ABCB1-1Δ variant is not only important regarding the use of multiple drugs, but the same causal variant was also discovered in multiple collie-like breeds such as the (miniature) Australian shepherd dog, English shepherd, McNab, Old English sheepdog, border collie, Shetland sheepdog, Wäller, and bearded collie (only one dog was genotyped as heterozygous in this last breed) [ 14 – 17 ]. Moreover, the variant appears in seemingly unrelated breeds like the longhaired whippet, silken Windhound [ 15 ], white Swiss shepherd [ 18 ], German shepherd [ 19 ], cocker spaniel, labradoodle [ 20 ], and crossbreeds [ 21 , 22 ]. Many population studies on the prevalence of the ABCB1-1Δ variant have been conducted all over the world [ 15 – 17 , 19 – 28 ] and high variant allele frequencies are mainly seen in the collie, (miniature) Australian shepherd, Shetland sheepdog, and longhaired whippet.…”