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Published online on August 2, 2004, 10.1073/pnas.0402374101 OPEN ACCESS ARTICLE


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Genetics
Breed distribution and history of canine mdr1-1{Delta}, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage

( allele age | Canis familiaris | drug sensitivity | identity by descent | P-glycoprotein )

Mark W. Neff *{dagger}, Kathryn R. Robertson *, Aaron K. Wong *, Noa Safra *, Karl W. Broman {ddagger}, Montgomery Slatkin {sect}, Katrina L. Mealey ¶, and Niels C. Pedersen *

*Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616; {ddagger}Department of Biostatistics, Johns Hopkins University, Baltimore, MD 21205; {sect}Department of Integrative Biology, University of California, Berkeley, CA 94720; and Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164

Edited by Arno G. Motulsky, University of Washington, Seattle, WA, and approved June 22, 2004 (received for review April 3, 2004)

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, mdr1-1{Delta}, 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 mdr1-1{Delta} 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 mdr1-1{Delta} 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.

{dagger}To whom correspondence should be addressed.

Mark W. Neff, E-mail: mwneff{at}ucdavis.edu

www.pnas.org/cgi/doi/10.1073/pnas.0402374101
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