Genome-wide association studies for multiple diseases of the German Shepherd Dog

Mamm Genome. 2012 Feb;23(1-2):203-11. doi: 10.1007/s00335-011-9376-9. Epub 2011 Nov 22.


The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (DM), congenital megaesophagus (ME), and pancreatic acinar atrophy (PAA). A locus on Chr 9 is strongly associated with pituitary dwarfism and is proximal to a plausible candidate gene, LHX3. Results for DM confirm a major locus encompassing SOD1, in which an associated point mutation was previously identified, but do not suggest modifier loci. Several SNPs on Chr 12 are associated with ME and a 4.7 Mb haplotype block is present in affected dogs. Analysis of additional ME cases for a SNP within the haplotype provides further support for this association. Results for PAA indicate more complex genetic underpinnings. Several regions on multiple chromosomes reach genome-wide significance. However, no major locus is apparent and only two associated haplotype blocks, on Chrs 7 and 12 are observed. These data suggest that PAA may be governed by multiple loci with small effects, or it may be a heterogeneous disorder.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping
  • Dog Diseases / genetics*
  • Dogs
  • Dwarfism, Pituitary / genetics
  • Dwarfism, Pituitary / veterinary*
  • Esophageal Achalasia / genetics
  • Esophageal Achalasia / veterinary*
  • Genetic Predisposition to Disease
  • Genome
  • Genome-Wide Association Study / veterinary*
  • LIM-Homeodomain Proteins / genetics
  • Pancreatic Diseases / genetics
  • Pancreatic Diseases / veterinary*
  • Polymorphism, Single Nucleotide
  • Spinal Cord Diseases / genetics
  • Spinal Cord Diseases / veterinary*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1
  • Transcription Factors / genetics


  • LIM-Homeodomain Proteins
  • Lhx3 protein
  • Transcription Factors
  • Superoxide Dismutase
  • Superoxide Dismutase-1