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Journal of Heredity Advance Access originally published online on June 15, 2005
Journal of Heredity 2005 96(7):727-734; doi:10.1093/jhered/esi086
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© The American Genetic Association. 2005. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org.

Genetic Mapping of Canine Multiple System Degeneration and Ectodermal Dysplasia Loci

Dennis P. O'Brien, Gary S. Johnson, Robert D. Schnabel, Shahnawaz Khan, Joan R. Coates, Gayle C. Johnson, and Jeremy F. Taylor

From the Department of Veterinary Medicine and Surgery (O'Brien, Coates), University of Missouri, 379 East Campus Drive, Columbia, MO 65211; Department of Veterinary Pathobiology (G. S. Johnson, Khan, G. C. Johnson), University of Missouri, Columbia, MO 65211; and Department of Animal Sciences (Schnabel, Taylor), University of Missouri, Columbia, MO 65211

Address correspondence to D. O'Brien at the address above, or e-mail: obriend{at}missouri.edu.

We characterized a movement disorder of Chinese Crested dogs clinically and pathologically indistinguishable from canine multiple system degeneration (CMSD) previously recognized in Kerry Blue Terriers. This fatal disease segregated as an autosomal recessive in a 51-dog pedigree of both breeds and their crosses. The occurrence of affected dogs among first-generation crosses demonstrated that the mutations causing multiple system degeneration in these breeds are allelic. The CMSD locus maps to CFA1 (LOD > 18) and haplotype analysis narrowed the CFA1 target region to a 15-Mb segment that contains orthologs of genes on HSA6, including PARK2, the gene for the ubiquitin ligase parkin. Mutations in human PARK2 cause the most common form of familial Parkinson's disease, autosomal recessive juvenile parkinsonism, which has clinical and pathological similarities to canine multiple system degeneration. A second phenotype, canine ectodermal dysplasia (CED), segregated in the pedigree as an autosomal dominant with homozygous lethality. Dogs with ectodermal dysplasia have a sparse hair coat and abnormal dentition that is characteristic of the "hairless" variety of Chinese Cresteds. CED mapped to a region of CFA17 (LOD > 14) containing orthologs from HSA2. EDAR, the gene for the ectodysplasin A1 receptor, occurs on HSA2 but was excluded as the cause of canine ectodermal dysplasia.


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