Bulldog dwarfism in Dexter cattle is caused by mutations in ACAN

Mamm Genome. 2007 Nov;18(11):808-14. doi: 10.1007/s00335-007-9066-9. Epub 2007 Oct 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans / genetics*
  • Aggrecans / metabolism
  • Animals
  • Base Sequence
  • Cattle
  • Cattle Diseases / genetics*
  • Cattle Diseases / metabolism
  • Chromosome Mapping
  • DNA / genetics
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • Dwarfism / genetics
  • Dwarfism / metabolism
  • Dwarfism / veterinary*
  • Exons
  • Female
  • Genes, Lethal
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Phenotype
  • Pregnancy
  • RNA Stability
  • RNA, Messenger / genetics

Substances

  • Aggrecans
  • DNA Primers
  • RNA, Messenger
  • DNA

Associated data

  • GENBANK/AY226857
  • GENBANK/AY226858
  • GENBANK/AY226859
  • GENBANK/AY226860
  • GENBANK/AY226861
  • GENBANK/AY226862
  • GENBANK/AY226863
  • GENBANK/AY226864
  • GENBANK/AY226865
  • GENBANK/AY226866
  • GENBANK/AY226867
  • GENBANK/AY226868
  • GENBANK/AY226869
  • GENBANK/AY226870
  • GENBANK/AY226871
  • GENBANK/AY226872
  • GENBANK/AY226873
  • GENBANK/AY226874
  • GENBANK/AY226875