Complex vertebral malformation (CVM)
Gene: SLC35A3
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.
Mutations:
Holstein Friesian mutation: Substitution, SLC35A3 gene; c.538 G > T, p.(V180F), chr.3.
Montbéliarde mutation: Substitution, SLC35A3 gene; G>T, p.(R25S), chr.3.
Medical systems: Skeletal, cardiac
Breeds: Holstein, Montbéliarde
Age of onset of symptoms: During foetal development, at birth.
Complex vertebral malformation (CVM) is a lethal genetic disease seen in the Holstein breed. Most affected fetuses are aborted before birth, while some calves are born prematurely, others are stillborn and very few calves are born alive. The disease is characterized by a deformed spine involving hemivertebrae, scoliosis and bone fusions (synsotosis) of vertebrae and ribs as well as joint flexions (arthrogryposis) of the front legs and sometimes the hind legs. Cardiac anomalies are present in about half of the affected calves, and can include septal defects, displaced aorta, and ventricular enlargement. Molecular studies have identified a mutation in the SLC35A3 gene, which codes for an enzyme that transports nucleotide sugars involved in the synthesis of certain glycoprotein and glycolipid molecules. These glycoprotein and glycolipid molecules are important for the embryonic formation of somite derivatives, i.e. vertebrae and ribs. Pedigree analysis identified an elite bull (Carlin-M Ivanhoe Bell) as responsible for the international dissemination of the mutation responsible for CVM via artificial insemination. In 1999, frequencies of carrier animals for CVM were estimated to be 31% for Holstein top sire bulls in Denmark. The availability of DNA testing to identify carrier animals has helped to reduce disease frequencies. For example, frequencies of carrier animals in Poland between 2004 and 2014 were 6.29%, whereas after 2016 the disease and the mutation had been eliminated.
References:
OMIA link: [1340-9913]
Kamiński S. (2023) Eradication of carriers of complex vertebral malformation (CVM) and brachyspina in Polish Holstein-Friesian bulls. Pol J Vet Sci 26(2):315-317. [pm/37389451]
Bourneuf E, Otz P, Pausch H, et al. (2017) Rapid discovery of de novo deleterious mutations in cattle enhances the value of livestock as model species. Sci Rep 7(1):11466. [pm/28904385]
Ruść A, Hering D, Puckowska P, et al. (2013) Screening of Polish Holstein-Friesian bulls towards eradication of complex vertebral malformation (CVM) carriers. Pol J Vet Sci 16(3):579-81. [pm/24195298]
Schütz E, Scharfenstein M, Brenig B. (2008) Implication of complex vertebral malformation and bovine leukocyte adhesion deficiency DNA-based testing on disease frequency in the Holstein population. J Dairy Sci 91:4854-9. [pm/19038961]
Thomsen B, Horn P, Panitz F, et al. (2006). A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation. Genome Res 16(1):97-105. [pm/16344554]
Revell, S. (2001) Complex vertebral malformation in a Holstein calf in the UK Veterinary Record 149(21):659-660. [pm/11764332]
Contributed by: Robin Delisle et Béatrice Laplante Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation, DWS)