Genotyping KIF1C (c.608G>A) Mutant Reveals a Wide Distribution of Progressive Ataxia in German Charolais Cattle

TL;DR

A study found a harmful KIF1C gene mutation in German Charolais cattle that causes fatal ataxia, with carriers showing better growth traits, suggesting genetic testing is needed to prevent its spread.

Contribution

The study reveals the prevalence of a lethal KIF1C mutation in German Charolais cattle and its unexpected association with superior growth traits.

Findings

The KIF1C mutation prevalence in German Charolais cattle is 11.75%, with homozygous carriers showing progressive ataxia.

Homozygous mutated cattle have significantly better estimated breeding values for daily weight gain and muscle conformation.

Two German Angus cattle were found to carry the KIF1C mutation heterozygously, suggesting the need for testing in this breed.

Abstract

Progressive ataxia is an autosomal recessive defect that is lethal due to the irreversible changes it causes to the brain and spinal cord. Only homozygous carriers of the mutated KIF1C allele manifest progressing clinical signs, mostly no earlier than 12–24 months of age. The objectives of this field study were to determine the prevalence of the mutated KIF1C allele, uncover its associations with growth and muscle conformation, and build awareness of this lethal condition among beef cattle breeders in Germany. A total of 1315 samples was sent in for mutation testing. Prevalence of the mutated KIF1C allele was 11.75%, resulting from 293 heterozygous and 8 homozygous mutant animals. Homozygous carriers of the mutated KIF1C allele showed a significant superiority in estimated breeding values for daily weight gain and muscle conformation. In order to reduce the frequency of the mutated KIF1C allele, genetic testing should be introduced for Charolais cattle and should be mandatory for all Charolais breeding bulls. It is important to create awareness of this condition among beef cattle breeders, in addition to the possibilities of preventing the number of affected animals. In addition, genetic testing of eight further beef, dual-purpose, or dairy cattle breeds revealed that two German Angus cattle showed heterozygous mutations for the KIF1C A-allele; therefore, we recommend genetic testing of German Angus to prevent the spread of the KIF1C allele.

Bovine progressive ataxia in Charolais cattle was first described in the 1970s; then, cases were reported in Charolais worldwide. A homozygous loss-of-function mutation within the KIF1C gene (c.608G>A) was found to be responsible for this neurodegenerative disease. The aim of this study was to determine whether the mutated KIF1C allele segregates in the German Charolais population and whether the estimated breeding values for growth and muscle conformation are associated with the mutated genotypes. Genetic test results of the KIF1C:c.608G>A variant were available for 1315 Charolais cattle from 35 herds located in Germany. In addition, 324 samples from eight other beef cattle breeds were tested for the mutated KIF1C allele. We were able to demonstrate that the KIF1C mutation is common, with a frequency of 11.75% in the German Charolais population. All but two of the eight (2/8 = 25%) homozygous mutated individuals showed clinical signs consistent with progressive ataxia. The estimated breeding values of muscle conformation in 200- and 365-day-old animals indicated a significant superiority for homozygous mutated animals when compared either with heterozygous or homozygous wild-type genotypes; this was also the case for heterozygous genotypes in comparison with homozygous wild-type genotypes. For the estimated breeding values of daily weight gain in 200- and 365-day-old animals, the significant differences between homozygous mutated and heterozygous or wild-type genotypes were in favour of the homozygous mutant animals. There were no differences in the estimated maternal breeding values among all three KIF1C genotypes. For the first time, two German Angus cattle carrying the KIF1C mutation heterozygous were detected. The breeders’ survey highlighted that increased awareness would facilitate increased conviction among breeders of the need for genetic testing in order to eliminate the lethal KIF1C allele.