title: Genetic mapping of canine multiple system degeneration and ectodermal dysplasia loci.
abstract: 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.
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211, USA. obriend@missour.edu
authors.forename: Dennis P
authors.initials: DP
authors.lastname: O'Brien
authors.forename: Gary S
authors.initials: GS
authors.lastname: Johnson
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schnabel
authors.forename: Shahnawaz
authors.initials: S
authors.lastname: Khan
authors.forename: Joan R
authors.initials: JR
authors.lastname: Coates
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Johnson
authors.forename: Jeremy F
authors.initials: JF
authors.lastname: Taylor
mesh_terms: D000818:Animals; D002524:Cerebellar Ataxia / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary; D002531:Cerebellum / Q000002:abnormalities / Q000503:physiopathology; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D017931:DNA Primers; D004283:Dog Diseases / Q000235:genetics* / Q000503:physiopathology; D004285:Dogs; D004476:Ectodermal Dysplasia / Q000235:genetics / Q000662:veterinary*; D006239:Haplotypes / Q000235:genetics; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary*; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D009069:Movement Disorders / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary*; D010375:Pedigree; D010641:Phenotype
chemical_list: D017931:DNA Primers