Mammalian Genome

, Volume 18, Issue 11, pp 808–814 | Cite as

Bulldog dwarfism in Dexter cattle is caused by mutations in ACAN

  • Julie A. L. CavanaghEmail author
  • Imke Tammen
  • Peter A. Windsor
  • John F. Bateman
  • Ravi Savarirayan
  • Frank W. Nicholas
  • Herman W. Raadsma


Bulldog dwarfism in Dexter cattle is one of the earliest single-locus disorders described in animals. Affected fetuses display extreme disproportionate dwarfism, reflecting abnormal cartilage development (chondrodysplasia). Typically, they die around the seventh month of gestation, precipitating a natural abortion. Heterozygotes show a milder form of dwarfism, most noticeably having shorter legs. Homozygosity mapping in candidate regions in a small Dexter pedigree suggested aggrecan (ACAN) as the most likely candidate gene. Mutation screening revealed a 4-bp insertion in exon 11 (2266_2267insGGCA) (called BD1 for diagnostic testing) and a second, rarer transition in exon 1 (−198C>T) (called BD2) that cosegregate with the disorder. In chondrocytes from cattle heterozygous for the insertion, mutant mRNA is subject to nonsense-mediated decay, showing only 8% of normal expression. Genotyping in Dexter families throughout the world shows a one-to-one correspondence between genotype and phenotype at this locus. The heterozygous and homozygous-affected Dexter cattle could prove invaluable as a model for human disorders caused by mutations in ACAN.


Premature Termination Codon Homozygosity Mapping Mutant mRNA Aggrecan mRNA Affected Calf 
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 the Australian and overseas Dexter breeders for their generous support in providing samples and information; B. Brenig and J. Williams for European samples; D. Palmer for field support; N. Baker and R. McNeil for help with the mRNA analyses; M. Jones, G. Attard, and C. Kristo for lab support; W. Horton for donation of primers; P. Gilbert for the donation of two carrier female Dexters; and the University of Sydney Veterinary Centre Camden for radiographs. This work was supported by Dexter Cattle Australia Inc. by way of an ARC Linkage grant, and by a theme grant from the Murdoch Children’s Research Institute.

Supplementary material


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Julie A. L. Cavanagh
    • 1
    Email author
  • Imke Tammen
    • 1
  • Peter A. Windsor
    • 2
  • John F. Bateman
    • 3
    • 4
  • Ravi Savarirayan
    • 5
    • 6
  • Frank W. Nicholas
    • 7
  • Herman W. Raadsma
    • 1
  1. 1.ReproGenThe University of SydneyCamdenAustralia
  2. 2.The University of SydneyCamdenAustralia
  3. 3.Musculoskeletal Disorders ThemeMurdoch Childrens Research Institute, Royal Children’s HospitalParkvilleAustralia
  4. 4.Department of PaediatricsUniversity of MelbourneParkvilleAustralia
  5. 5.Clinical Genetics UnitRoyal Children’s HospitalParkvilleAustralia
  6. 6.Southern Cross Bone Dysplasia CentreGenetic Health Services Victoria, Royal Children’s HospitalParkvilleAustralia
  7. 7.ReproGenThe University of SydneyCamdenAustralia

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