Mammalian Genome

, Volume 23, Issue 1–2, pp 203–211 | Cite as

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

  • Kate L. Tsai
  • Rooksana E. Noorai
  • Alison N. Starr-Moss
  • Pascale Quignon
  • Caitlin J. Rinz
  • Elaine A. Ostrander
  • Jörg M. Steiner
  • Keith E. Murphy
  • Leigh Anne Clark


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.


Amyotrophic Lateral Sclerosis Exocrine Pancreatic Insufficiency National Human Genome Research Institute Exocrine Pancreatic Insufficiency Combine Pituitary Hormone Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank the American Kennel Club Canine Health Foundation for supporting this work and the Intramural Program of the National Human Genome Research Institute. We are grateful to the numerous dog owners and veterinarians who provided samples.

Supplementary material

335_2011_9376_MOESM1_ESM.tif (24.9 mb)
Supplementary Fig. 1 Principal component analysis of 98 GSDs with PAA versus 79 healthy control GSDs. The x axis is principal component 1 and the y axis is principal component 2. Both populations appear to be evenly distributed throughout the cluster and no significant stratification was observed (TIFF 25530 kb)
335_2011_9376_MOESM2_ESM.doc (252 kb)
Supplementary material 2 (DOC 70 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kate L. Tsai
    • 1
  • Rooksana E. Noorai
    • 1
  • Alison N. Starr-Moss
    • 1
  • Pascale Quignon
    • 2
    • 3
  • Caitlin J. Rinz
    • 1
  • Elaine A. Ostrander
    • 2
  • Jörg M. Steiner
    • 4
  • Keith E. Murphy
    • 1
  • Leigh Anne Clark
    • 1
  1. 1.Department of Genetics and BiochemistryCollege of Agriculture, Forestry and Life Sciences, Clemson UniversityClemsonUSA
  2. 2.Cancer Genetics BranchNational Human Genome Research Institute, National Institutes of HealthBethesdaUSA
  3. 3.Institut de Génétique et Développement de RennesCNRS-UMR6061, Université de Rennes 1Rennes CedexFrance
  4. 4.Department of Small Animal Clinical SciencesCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationUSA

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