title: A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse.
abstract: Labrador retrievers are the most common dog breed in the world, with over 200,000 new kennel club registrations per year. The syndrome of exercise-induced collapse (EIC) in this breed is manifested by muscle weakness, incoordination and life-threatening collapse after intense exercise. Using a genome-wide microsatellite marker scan for linkage in pedigrees, we mapped the EIC locus to canine chromosome 9. We then used SNP association and haplotype analysis to fine map the locus, and identified a mutation in the dynamin 1 gene (DNM1) that causes an R256L substitution in a highly conserved region of the protein. This first documented mammalian DNM1 mutation is present at a high frequency in the breed and is a compelling candidate causal mutation for EIC, as the dynamin 1 protein has an essential role in neurotransmission and synaptic vesicle endocytosis.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota 55108, USA. patte037@umn.edu
authors.forename: Edward E
authors.initials: EE
authors.lastname: Patterson
authors.forename: Katie M
authors.initials: KM
authors.lastname: Minor
authors.forename: Anna V
authors.initials: AV
authors.lastname: Tchernatynskaia
authors.forename: Susan M
authors.initials: SM
authors.lastname: Taylor
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
authors.forename: Kari J
authors.initials: KJ
authors.lastname: Ekenstedt
authors.forename: James R
authors.initials: JR
authors.lastname: Mickelson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D034284:Dynamin I / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D018908:Muscle Weakness / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D010805:Physical Conditioning, Animal; D020641:Polymorphism, Single Nucleotide; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: D034284:Dynamin I