October 11, 2022
In a letter from American-International Charolais Association Vice President Dr. Clint Rusk, the AICA Executive Committee was made aware of a genetic variant in Charolais cattle called Progressive Ataxia. After consultation with the Executive Committee, President Eddy Loggains appointed a Subcommittee of the Breed Improvement Committee to investigate the impact of the variant on Charolais cattle. The subcommittee requested an opportunity to interact with genetic consultants from major research institutions with expertise in this specific genetic variant.
These genetic consultants include: Dr. Jon Beever – University of Tennessee, Kelli Retallick – President of Angus Genetics Inc., Dr. Robert Schnabel – University of Missouri and Dr. David Steffen – University of Nebraska-Lincoln. After meeting with the genetic consultants and getting answers to their questions about this genetic variant, the Subcommittee considered testing strategies and recommendations that would be beneficial to AICA members. Here are some of the facts the Subcommittee has learned about Progressive Ataxia and its impact on Charolais and Charolais-Influenced cattle.
Progressive ataxia is an incoordination observed, starting in the rear legs, of young adult cattle. The disease progresses over a period of weeks to months until cattle are unable to stand up without assistance. The incidence of this disease and mutation in the Charolais breed has been traced back to an influential sire born in 1964. Palmer et. al., described this disorder in the United Kingdom in 1975. The pattern Palmer described was consistent with a recessive trait. Each parent had to be a carrier of an abnormal gene variant. Cases recognized in the United States were infrequent during the ensuing four decades.
The recent, small but notable, spike in reported cases lead the AICA to re-evaluate the significance of the disease to the breed. A 2018 French paper, published in PLOS-Genetics, describes the responsible allele variant. The AICA had this peer review study further evaluated by multiple independent geneticists and each concurred the study is credible, and the mutant variant is responsible for disease development. The ability to test for the mutant variant became available after the French publication. Testing is currently available in the USA, through Neogen and at the UC-Davis genetic testing laboratory. The test at Neogen is on the 100K chip and data existed allowing us to estimate mutant variant frequency in the USA.
After meeting with genetic consultants and learning about Progressive Ataxia, the AICA subcommittee, mentioned earlier, has begun to formulate a response plan to be presented to the Breed Improvement Committee for consideration at their Fall meeting on October 19th. The goal of the plan is to minimize or eliminate economic losses due to the occurrence of clinically affected cattle.
Testing, recording, and communicating test results so the mutant variant frequency can be reduced, and mating of carrier-to-carrier cattle can be avoided, is the industry standard approach for addressing deleterious gene variants. This will not affect registration status of your animals. The association will work to help identify animals with the pedigree potential to carry the variant to minimize testing costs for the membership.
An outline of the testing requirements follows. The AICA website provides access to additional information on the disease, testing requirements, plans for recording and communicating test results and links to the French paper that references the peer reviewed science published regarding this disease. The AICA has arranged for Dr. Steffen at the University of Nebraska Veterinary Diagnostic Center to assist with diagnostic investigations of any other suspect inherited abnormalities in Charolais cattle. [email protected] is the best method to contact Dr. Steffen.
Frequently asked questions
What is progressive ataxia?
The disease causes incoordination in Charolais cattle. The calves are born clinically normal. Onset of the disease is typically seen at 18-24 months-of-age. Early onset cases have been reported for animals as young as 8 months old and some cases have been reported for animals who are 30 months-of-age at onset, but these reports are infrequent. Affected cattle are typically culled by 36 months-of-age. French surveys determined no genotyped cattle older than 30 months-of-age were homozygous for the variant allele. Incoordination is first noticeable in the rear limbs which can exhibit spastic movements. Weaving, stumbling, and toe dragging are common. Affected cattle may have difficulty getting up and as front legs get affected, they can become unable to rise. Females may experience pulsating urination. Progression takes several weeks to a few months. Initial symptoms can be similar to rabies, other infections or an injury. Infections progress faster and injuries are generally static or injured animals slowly recover.
What is the cause of progressive ataxia?
The disease is caused by a single substitution, c.608G>A, in the KIF1C gene. This results in an amino acid substitution in a highly conserved region of the gene. A splicing defect occurs during transcription and the result is absence of the KIF1C protein in the brain. This protein is important in cytoplasmic structure and transport in the cells that form myelin in the brain and spinal cord. Myelin is the insulating wrap created by cells called oligodendroglia that wrap around nerve fibers and regulate signal movement along nerve pathways. The absence of this protein disables maintenance of the myelin and accumulation of cellular materials in the oligodendroglia forming plaques in the brain and spinal cord. Pathologists can recognize these plaques microscopically for diagnosis. The abnormal myelin leaves some nerve fibers exposed and changes nerve conduction by changing myelin structure. To be affected, a calf must be born homozygous for the variant allele. Both parents must have the variant allele for the calf to be affected. A genotypic affected, but preclinical bull could produce a high number of carriers and more frequent affected offspring when mated to a normal and a carrier heifer respectively.
How can I test my breeding stock?
If your bulls or females have been genotyped on Neogen’s 100K chip, the PA status of the animals may be available now. Please contact Maggie Smithee at AICA for instructions on how to proceed. There is also a stand-alone test at the UC-Davis Genetics Lab. The test requires a DNA source such as: a small piece of tissue, 20 hairs plus roots, or blood collected in an EDTA (purple top) tube. Each lab has a preference for how they receive DNA. Please refer to their website for sampling and submitting instructions.
UC-Davis reports animal genotype as normal - NN, Carrier - NA, or homozygous for the variant - AA. The AICA will note animals to be progressive ataxia free - PAF, progressive ataxia carrier - PAC, or progressive ataxia affected - PAA. If affected animals are sampled at a young age, they may be preclinical and appear normal. The ability to test will allow breeders to segregate this undesired trait from the many good attributes of high valued females or bulls by selecting PAF offspring from PAC or PAA sires or dams.
How is progressive ataxia passed down, and what does it mean if my animal is a carrier of the variant?
Progressive ataxia is an autosomal recessive trait. This means for an animal to be affected, or to express the phenotype, they must be carrying two copies of the variant.
Gender is not relevant in the examples shown above and can be reversed in these examples. Carriers were found in one study to have good muscling. Their use in a terminal crossing situation may have merit as a salvage step. Offspring from three of these scenarios will result in some normal calves who are non-carriers and thus, can be tested free and utilized to capture other good traits from a desirable genetic line.
Since July 1, 2020, Neogen tested over 11,000 Charolais animals. Eighty-four percent of these animals tested free of Progressive Ataxia. Last year, a purebred Charolais breeder sent samples to Neogen from 134 cows. Neogen tested these samples on the 100K chip. This same breeder recently requested the PA status of the 134 cows mentioned above. One hundred twenty-one (90%) of the cows are PA free and 13 (10%) are PA carriers.
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