title: Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy.
abstract: BACKGROUND
  Previous reports associated 2 mutant SOD1 alleles (SOD1:c.118A and SOD1:c.52T) with degenerative myelopathy in 6 canine breeds. The distribution of these alleles in other breeds has not been reported.
  
  
  OBJECTIVE
  To describe the distribution of SOD1:c.118A and SOD1:c.52T in 222 breeds.
  
  
  METHODS
  DNA from 33,747 dogs was genotyped at SOD1:c.118, SOD1:c.52, or both. Spinal cord sections from 249 of these dogs were examined.
  
  
  METHODS
  Retrospective analysis of 35,359 previously determined genotypes at SOD1:c.118G>A or SOD1:c.52A>T and prospective survey to update the clinical status of a subset of dogs from which samples were obtained with a relatively low ascertainment bias.
  
  
  RESULTS
  The SOD1:c.118A allele was found in cross-bred dogs and in 124 different canine breeds whereas the SOD1:c.52T allele was only found in Bernese Mountain Dogs. Most of the dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A homozygotes, but 8 dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A/G heterozygotes and had no other sequence variants in their SOD1 amino acid coding regions. The updated clinical conditions of dogs from which samples were obtained with a relatively low ascertainment bias suggest that SOD1:c.118A homozygotes are at a much higher risk of developing degenerative myelopathy than are SOD1:c.118A/G heterozygotes.
  
  
  CONCLUSIONS
  We conclude that the SOD1:c.118A allele is widespread and common among privately owned dogs whereas the SOD1:c.52T allele is rare and appears to be limited to Bernese Mountain Dogs. We also conclude that breeding to avoid the production of SOD1:c.118A homozygotes is a rational strategy.
authors: Department of Veterinary Pathology, University of Missouri, Columbia, MO.
authors: R
authors: R
authors: Zeng
authors: J R
authors: JR
authors: Coates
authors: G C
authors: GC
authors: Johnson
authors: L
authors: L
authors: Hansen
authors: T
authors: T
authors: Awano
authors: A
authors: A
authors: Kolicheski
authors: E
authors: E
authors: Ivansson
authors: M
authors: M
authors: Perloski
authors: K
authors: K
authors: Lindblad-Toh
authors: D P
authors: DP
authors: O'Brien
authors: J
authors: J
authors: Guo
authors: M L
authors: ML
authors: Katz
authors: G S
authors: GS
authors: Johnson
mesh_terms: D000483:Alleles; D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006720:Homozygote; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000662:veterinary*; D020125:Mutation, Missense; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D013482:Superoxide Dismutase
keywords: Amyotrophic lateral sclerosis; Cytoplasmic aggregates; DNA test; Spinal cord