Mammalian Genome

, Volume 18, Issue 11, pp 808–814

Bulldog dwarfism in Dexter cattle is caused by mutations in ACAN

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

DOI: 10.1007/s00335-007-9066-9

Cite this article as:
Cavanagh, J.A.L., Tammen, I., Windsor, P.A. et al. Mamm Genome (2007) 18: 808. doi:10.1007/s00335-007-9066-9

Abstract

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.

Supplementary material

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Julie A. L. Cavanagh
    • 1
  • 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