Mammalian Genome

, Volume 21, Issue 7–8, pp 398–408 | Cite as

COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia

  • Orly Goldstein
  • Richard Guyon
  • Anna Kukekova
  • Tatyana N. Kuznetsova
  • Susan E. Pearce-Kelling
  • Jennifer Johnson
  • Gustavo D. Aguirre
  • Gregory M. Acland


Oculoskeletal dysplasia segregates as an autosomal recessive trait in the Labrador retriever and Samoyed canine breeds, in which the causative loci have been termed drd1 and drd2, respectively. Affected dogs exhibit short-limbed dwarfism and severe ocular defects. The disease phenotype resembles human hereditary arthro-ophthalmopathies such as Stickler and Marshall syndromes, although these disorders are usually dominant. Linkage studies mapped drd1 to canine chromosome 24 and drd2 to canine chromosome 15. Positional candidate gene analysis then led to the identification of a 1-base insertional mutation in exon 1 of COL9A3 that cosegregates with drd1 and a 1,267-bp deletion mutation in the 5′ end of COL9A2 that cosegregates with drd2. Both mutations affect the COL3 domain of the respective gene. Northern analysis showed that RNA expression of the respective genes was reduced in affected retinas. These models offer potential for studies such as protein-protein interactions between different members of the collagen gene family, regulation and expression of these genes in retina and cartilage, and even opportunities for gene therapy.


Labrador Retriever COL3 Domain COL9A3 Mutation Multiple Epiphyseal Dysplasia Stickler Syndrome 
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.



The authors thank Julie Jordan and the staff of the RDS facility for excellent technical assistance. Blood samples with pedigrees and clinical reports were provided by Ms. Sue Bailey and Ms. Nancy Scholz for selected Labrador retriever dogs. Leah Seman, Beth A. Tallentire, and Glen Adams, breeders and owners of samoyed dogs, were immensely cooperative and helpful and are gratefully acknowledged. This work was supported by NIH grant EY006855, The Foundation Fighting Blindness, and the Morris Animal Foundation.


G. M. Acland and G. D. Aguirre are co-owners of Optigen, LLC (Ithaca, NY, USA) which has licensed the technology for DNA testing of dogs with OSD from Cornell University.

Supplementary material

335_2010_9276_MOESM1_ESM.doc (210 kb)
Supplementary material 1 (DOC 209 kb)


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Orly Goldstein
    • 1
  • Richard Guyon
    • 2
  • Anna Kukekova
    • 1
  • Tatyana N. Kuznetsova
    • 4
  • Susan E. Pearce-Kelling
    • 1
    • 3
  • Jennifer Johnson
    • 1
  • Gustavo D. Aguirre
    • 4
  • Gregory M. Acland
    • 1
  1. 1.Baker Institute for Animal Health, College of Veterinary MedicineCornell UniversityIthacaUSA
  2. 2.Faculté de MédecineInstitut de Génétique et DéveloppementRennesFrance
  3. 3.Optigen, LLCIthacaUSA
  4. 4.School of Veterinary MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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