Mammalian Genome

, Volume 18, Issue 11, pp 808–814

Bulldog dwarfism in Dexter cattle is caused by mutations in ACAN

Authors

    • ReproGenThe University of Sydney
  • Imke Tammen
    • ReproGenThe University of Sydney
  • Peter A. Windsor
    • The University of Sydney
  • John F. Bateman
    • Musculoskeletal Disorders ThemeMurdoch Childrens Research Institute, Royal Children’s Hospital
    • Department of PaediatricsUniversity of Melbourne
  • Ravi Savarirayan
    • Clinical Genetics UnitRoyal Children’s Hospital
    • Southern Cross Bone Dysplasia CentreGenetic Health Services Victoria, Royal Children’s Hospital
  • Frank W. Nicholas
    • ReproGenThe University of Sydney
  • Herman W. Raadsma
    • ReproGenThe University of Sydney
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