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Haplotype structure and heterozygosity around the fragile foal syndrome variant in Swedish Warmblod horses.
Abstract: Fragile foal syndrome (FFS) is a disease caused by a recessive lethal missense mutation in the PLOD1 gene located on ECA2. Despite its harmful effect, a relatively high frequency of FFS carriers was observed in Warmblood breeds spanning from 7.4% in a random sample of Swedish Warmblood breed to 17% in the Hanoverian and Danish Warmblood, indicating potential heterozygous advantage. Balancing selection can be further studied based on haplotype blocks and via detection of heterozygosity-rich region (ROHet) around the target of selection. In this study we evaluated the presence of haplotype blocks and ROHet on ECA2 in 380 Swedish Warmblood horses. We compared the results of ROHet with the rest of the genome. On average, 11.7 heterozygosity rich regions were identified per horse on ECA2, with no significant difference in numbers and length compared to what was found in other chromosomes. A unique haplotype block containing 28 markers was found in the FFS haplotype, while there were several haplotype blocks in the non-carrier haplotype. This unique haplotype block mostly spanned the region upstream of the PLOD1 gene and included the MFN2 gene. The presence of this extended haplotype, shared by multiple individuals and including both the FFS variant and the MFN2 gene, suggests that this region may be under selection. While we did not find a clear heterozygosity-rich region around the FFS variant, the extended haplotype may reflect either a signature of balancing selection or linkage disequilibrium with a positively selected variant in MFN2, PLOD1, or nearby loci.
© 2025 The Author(s). Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.
Publication Date: 2025-06-17 PubMed ID: 40524478PubMed Central: PMC12171683DOI: 10.1111/age.70022Google 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 article investigates Fragile Foal Syndrome in Swedishs Warmblood horse, validating the existence of haplotype blocks and regions rich in heterozygosity (ROHet) on their chromosome ECA2. Results did not indicate a clear ROHet around the FFS gene variant, but a unique haplotype block was found, suggesting potential selection in that region.
Understanding the Research Topic
- Fragile Foal Syndrome (FFS) is a lethal genetic condition in horses, resulting from a missense mutation in the PLOD1 gene.
- The high frequency of FFS carriers in Warmblood breeds suggests a potential heterozygous advantage.
- This high frequency of carriers can be investigated further through haplotype blocks (specific set of gene variants, or alleles, on a single chromosome) and detection of regions that show higher heterozygosity (ROHet).
About This Study
- The researchers examined these haplotype blocks and ROHet in 380 Swedish Warmblood horses.
- They also compared the results with those from the rest of the horse genome.
Results and Analysis
- The researchers identified on average 11.7 heterozygosity-rich regions per horse on ECA2. The numbers and lengths of these regions were consistent with those found on other chromosomes.
- A unique haplotype block, including 28 markers, was discovered in the FFS haplotype. Conversely, multiple haplotype blocks were identified in the non-carrier haplotype.
- This unique haplotype block typically spanned an area upstream of the PLOD1 gene and included the MFN2 gene.
Implication of Research Findings
- The presence of this extensive haplotype, shared by multiple individuals and comprising both the FFS variant and the MFN2 gene, suggests this region may be under selection.
- While no clear heterozygosity-rich region was found around the FFS variant, the extensive haplotype might reflect a balancing selection signature or link to a positively selected variant in MFN2, PLOD1, or nearby areas.
- This suggests there may be more complex genetic activity connected to FFS, possibly including other genes or factors beyond just the PLOD1 mutation.
Cite This Article
APA
Ablondi M, Eriksson S, Mikko S.
(2025).
Haplotype structure and heterozygosity around the fragile foal syndrome variant in Swedish Warmblod horses.
Anim Genet, 56(3), e70022.
https://doi.org/10.1111/age.70022 Publication
Researcher Affiliations
- Department of Veterinary Science, Università degli Studi di Parma, Parma, Italy.
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
MeSH Terms
- Animals
- Haplotypes
- Horses / genetics
- Heterozygote
- Horse Diseases / genetics
- Sweden
- Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / genetics
- Mutation, Missense
Grant Funding
- 2020-01333 / Svenska Forskningsrådet Formas
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 19 references
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