Dwarfism (GON4L-related)

Gene: GON4L

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Deletion, GON4L gene: c.4287delC, p(Glu1430Lys frameshift STOP 66), exon20, Chr.3.

Medical system: Skeletal

Breed: Simmental (Fleckvieh)

Age of onset of symptoms: From birth

Hereditary dwarfism is reported in a number of cattle breeds and currently several gene mutations have been characterized that are responsible for the phenotype. In general, the dwarfism can be proportionate, where the animal is small, but body size and leg length maintain their respective proportions, or it can be disproportionate, where legs are shortened in a disproportionate fashion compared to body size.

A phenotype of proportionate dwarfism was identified in 27 Fleckvieh calves with normal parents but sired by a particular artificial insemination bull. Calves were born small and underweight. They had large heads with craniofacial deformities as well as spinal anomalies and wrinkled skin. They grew poorly but were otherwise healthy. Molecular studies identified a mutation in the GON4L gene, which codes for a nuclear protein believed to be a transcriptional factor. Pedigree studies identified a common ancestor born in 1959. In a survey of 3855 animals a carrier frequency of 2.4% was observed. A DNA test is available such that this mutation can now be eliminated from the breed by judicious selective breeding.