Breed distribution and history of canine mdr1-1Delta, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage.
A mutation in the canine multidrug resistance gene, MDR1, has previously been associated with drug sensitivities in two breeds from the collie lineage. We exploited breed phylogeny and reports of drug sensitivity to survey other purebred populations that might be genetically at risk. We found that the same allele, mdr1-1Delta, segregated in seven additional breeds, including two sighthounds that were not expected to share collie ancestry. A mutant haplotype that was conserved among affected breeds indicated that the allele was identical by descent. Based on breed histories and the extent of linkage disequilibrium, we conclude that all dogs carrying mdr1-1Delta are descendants of a dog that lived in Great Britain before the genetic isolation of breeds by registry (ca. 1873). The breed distribution and frequency of mdr1-1Delta have applications in veterinary medicine and selective breeding, whereas the allele's history recounts the emergence of formally recognized breeds from an admixed population of working sheepdogs.
Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. mwneff@ucdavis.edu
Mark W
MW
Neff
Kathryn R
KR
Robertson
Aaron K
AK
Wong
Noa
N
Safra
Karl W
KW
Broman
Montgomery
M
Slatkin
Katrina L
KL
Mealey
Niels C
NC
Pedersen
D000483:Alleles; D000818:Animals; D001947:Breeding / Q000266:history; D004283:Dog Diseases / Q000139:chemically induced / Q000235:genetics; D004285:Dogs / Q000235:genetics*; D005787:Gene Frequency; D019450:Genes, MDR / Q000235:genetics* / Q000502:physiology; D006239:Haplotypes; D049711:History, Modern 1601-; D007559:Ivermectin / Q000009:adverse effects; D015810:Linkage Disequilibrium; D009154:Mutation; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000235:genetics / Q000662:veterinary; D010597:Pharmacogenetics; D010802:Phylogeny
D007559:Ivermectin