Dwarfism, Bulldog calf (ACAN-related)

Gene: ACAN

Transmission: Autosomal dominant (incomplete)

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease. Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation. One or both of the parents of an animal with the mutation is a carrier of the mutation. Dominant mutations that are homozygote lethal can be maintained within a population in the heterozygous form.

Mutations:

Mutation BD1: Insertion, ACAN gene: c.2266_2267 ins.GGCA, exon11, Chr.21.

Mutation BD2: Substitution, ACAN gene: c.-198C>T, exon1, Chr.21.

Mutation Zebu: Insertion, ACAN gene: c.5686 ins.C, p.(Val1898 frameshift STOP 9), Chr.21.

Medical system: Skeletal, musculoskeletal

Breeds: Dexter, Highland, Zebu

Age of onset of symptoms: Foetal (7 months of gestation)

For over a century a congenital anomaly referred to as the bulldog calf syndrome has been described in Dexter and Highland cattle breeds. Heterozygote animals have a phenotype of somewhat shortened legs, a trait sometimes favored by breeders. The homozygous condition leads to congenital lethal chondrodysplasia with late term abortion of the foetus, the so-called bulldog calf. Aborted foetuses display extremely disproportionate achondrodysplastic dwarfism, with very short legs, craniofacial defects including bulging head, cleft palate and a protruding lower jaw, and a shortened vertebral column. Molecular studies on two aborted Dexter foetuses identified two mutations within the ACAN gene as being responsible for the phenotype. The ACAN gene codes for the Aggrecan protein which plays a critical role as a proteoglycan in cartilage formation and function. More recently, a separate mutation in the ACAN gene was identified in Zebu cattle as being responsible for a similar lethal condition when homozygote. DNA tests are now available to allow breeders to identify carrier animals such that this genetic disease can be eliminated from their breeds.