Breed distribution and history of canine mdr1-1Δ a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage

Mark W. Neff, Kathryn R. Robertson, Aaron K. Wong, Noa Safra, Karl W. Broman, Montgomerg Slatkin, Katrina L. Mealey, Niels C Pedersen

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

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, mdr1-1Δ, 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 mdr1-1Δ 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 mdr1-1Δ 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 sheep-dogs.

Original languageEnglish (US)
Pages (from-to)11725-11730
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number32
DOIs
StatePublished - Aug 10 2004

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Pharmacogenetics
Canidae
Alleles
Dogs
Mutation
MDR Genes
Veterinary Medicine
Linkage Disequilibrium
Phylogeny
Pharmaceutical Preparations
Haplotypes
Population
Registries
Sheep

Keywords

  • Allele age
  • Canis familiaris
  • Drug sensitivity
  • Identity by descent
  • P-glycoprotein

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Breed distribution and history of canine mdr1-1Δ a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. / Neff, Mark W.; Robertson, Kathryn R.; Wong, Aaron K.; Safra, Noa; Broman, Karl W.; Slatkin, Montgomerg; Mealey, Katrina L.; Pedersen, Niels C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 32, 10.08.2004, p. 11725-11730.

Research output: Contribution to journalArticle

Neff, Mark W. ; Robertson, Kathryn R. ; Wong, Aaron K. ; Safra, Noa ; Broman, Karl W. ; Slatkin, Montgomerg ; Mealey, Katrina L. ; Pedersen, Niels C. / Breed distribution and history of canine mdr1-1Δ a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 32. pp. 11725-11730.
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