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A missense mutation in the KCNE4 gene is not predictive of equine anhidrosis.
Abstract: Anhidrosis is defined as a decreased or absent ability to sweat in response to heat and exercise. In horses, this condition can increase the risk of life-threatening hyperthermia. A prior study has suggested that equine anhidrosis is associated with a missense variant (rs68643109) in the Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 4 (KCNE4) gene. This project aimed to validate this association in a population of well-phenotyped horses and to determine the allele frequency of this variant in publicly available whole-genome sequence data. Fifty horses within the University of California Davis Center for Equine Health herd were evaluated for anhidrosis using a series of intradermal terbutaline injections. From existing whole-genome sequence data, the rs68643109 genotype of each horse was identified. When stimulated with terbutaline, all 50 horses produced sweat. All three genotypes at rs68643109 were present in this population of horses; the allele previously associated with anhidrosis (G) was present at a frequency of 0.72. No statistical difference in total sweat score was found (p = 0.31). In whole-genome sequences from 820 other horses reported across three prior studies, the alternative (candidate) allele frequency was similarly high, ranging from 0.52 to 0.68. Since all 50 horses tested in our population produced sweat regardless of genotype, and the previously associated allele is present at a high frequency across datasets, these data fail to validate the missense variant within the KCNE4 gene as causative of or contributing to equine anhidrosis.
© 2025 The Author(s). Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.
Publication Date: 2025-02-16 PubMed ID: 39953936PubMed Central: PMC11829550DOI: 10.1111/age.70004Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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This research aimed to assess if a specific genetic mutation in horses is linked to anhidrosis, a condition where a horse cannot sweat effectively. However, the results did not validate the claim that equine anhidrosis is caused by a missense variant in the KCNE4 gene.
Research Objective
- The primary objective of this research study was to verify the relationship between a particular genetic mutation (a missense variant, rs68643109), found in the KCNE4 gene of horses, and the condition of anhidrosis.
- Anhidrosis is a condition where horses lack the ability to sweat effectively, which can raise the risk of potentially lethal overheating (hyperthermia).
- The authors aimed to confirm the alleged link by studying a well-phenotyped population of horses at the University of California Davis Center for Equine Health.
Research Methodology
- For this study, a total of 50 horses from the UC Davis Centre for Equine Health herd were selected.
- Each horse was tested for anhidrosis by administering a series of intradermal injections of terbutaline, which is an agent that stimulates sweating.
- Using available whole-genome sequence data, the presence of the alleged genetic mutation (rs68643109) was identified in each horse.
- The same study was conducted on genomic data of 820 other horses sourced from three previous studies.
Research Findings
- Results showed that all 50 horses were able to produce sweat when injected with terbutaline. This finding was consistent across all horses, regardless of the rs68643109 genotype.
- In addition, it was found that the allele G, which was previously alleged to cause anhidrosis, was present in 72% of the tested population.
- A comparison of total sweat score showed no significant differences across the genotype variations, disconfirming any meaningful correlation between anhidrosis and the rs68643109 genotype.
- In the genome sequences from the 820 other horses, it was found that the alternative allele frequency ranged from 0.52 to 0.68, reinforcing that the presence of the missense variant in the KCNE4 gene is not linked causally or contributory to anhidrosis.
Research Conclusion
- Based on these findings, the research study concluded that there is no solid evidence to substantiate the hypothesis that a missense mutation (rs68643109) in the KCNE4 gene might cause, or is a significant contributor to, equine anhidrosis.
- This study emphasizes the importance of examining specific genetic markers in well-phenotyped populations to truly understand the role of genetics in disease expression.
Cite This Article
APA
van der Graaf L, Leigh W, Szmatoła T, Roberts K, Ryan S, Brown B, Van Buren S, Finno CJ, Petersen JL.
(2025).
A missense mutation in the KCNE4 gene is not predictive of equine anhidrosis.
Anim Genet, 56(1), e70004.
https://doi.org/10.1111/age.70004 Publication
Researcher Affiliations
- Department of Population Health and Reproduction, University of California-Davis, School of Veterinary Medicine, Davis, California, USA.
- Department of Population Health and Reproduction, University of California-Davis, School of Veterinary Medicine, Davis, California, USA.
- Department of Basic Sciences, University of Agriculture in Krakow, Kraków, Poland.
- Department of Population Health and Reproduction, University of California-Davis, School of Veterinary Medicine, Davis, California, USA.
- Department of Population Health and Reproduction, University of California-Davis, School of Veterinary Medicine, Davis, California, USA.
- Department of Population Health and Reproduction, University of California-Davis, School of Veterinary Medicine, Davis, California, USA.
- Department of Population Health and Reproduction, University of California-Davis, School of Veterinary Medicine, Davis, California, USA.
- Department of Population Health and Reproduction, University of California-Davis, School of Veterinary Medicine, Davis, California, USA.
- Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
MeSH Terms
- Animals
- Horses / genetics
- Mutation, Missense
- Horse Diseases / genetics
- Potassium Channels, Voltage-Gated / genetics
- Hypohidrosis / genetics
- Hypohidrosis / veterinary
- Male
- Female
- Gene Frequency
- Genotype
Grant Funding
- UC Davis Center for Equine Health
Conflict of Interest Statement
None declared.
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