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Prevalence of the RAPGEF5 c.2624C>A and PLOD1 c.2032G>A variants associated with equine familial isolated hypoparathyroidism and fragile foal syndrome in the US Thoroughbred population (1988-2019).
Abstract: Equine familial isolated hypoparathyroidism (EFIH) and fragile foal syndrome (FFS) are both fatal recessive conditions reported in Thoroughbred foals. The causal variants for EFIH (RAPGEF5 c.2624C>A; EquCab3.0. chr4: g.54108297G>T) and FFS (PLOD1 c.2032G>A; EquCab3.0, chr2: g.39927817) were recently reported. Prevalence assessment for these variants in a large cohort of samples is needed to provide evidence-based recommendations for genetic testing. Objective: To estimate the frequency of the EFIH and FFS variant alleles in the United States Thoroughbred population between 1988 and 2019, and determine whether these are recent mutations or are increasing in frequency due to current breeding practices. Methods: Population allele frequency study. Methods: Genomic DNA from hair and serum samples were genotyped for the EFIH and FFS. Allele frequencies between cohorts, based on year of birth (1988-2000, n = 728) and (2001-2019, n = 1059), as well as across the seven geographical regions of the United States were compared by Fisher's Exact tests. Results: EFIH and FFS allele frequencies were not significantly different between the two time points studied (0.008 and 0.004, respectively, in the older cohorts and 0.008 and 0.009 in most recent years). No EFIH or FFS homozygotes were detected. A sample from 1992 was identified as a carrier for EFIH and one from 1993 a carrier for FFS. Non-significant changes in geographical distribution of carriers for both traits were observed. Conclusions: The earliest samples available for study were from foals born in 1988. Conclusions: The EFIH and FFS variants are present at low frequency in the United States Thoroughbred population but are not recent mutations. There is no evidence to support changes in allele frequency over time. However, given the closed studbook and breeding practices, continued monitoring of breed allele frequencies and genetic testing is recommended to avoid the mating of carriers and production of affected foals.
© 2022 EVJ Ltd.
Publication Date: 2022-10-18 PubMed ID: 36199159PubMed Central: PMC10073348DOI: 10.1111/evj.13883Google 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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The research article studies the prevalence of certain genetic variants related to fatal conditions, termed Equine familial isolated hypoparathyroidism (EFIH) and fragile foal syndrome (FFS), in Thoroughbred foals. The article aims to understand the variants’ frequency over time and if they are influenced by breeding practices.
Identification of genetic issues in thoroughbred foals
In this study, the researchers focused on exploring the variants associated with two fatal recessive Thoroughbred foals’ conditions—Equine familial isolated hypoparathyroidism (EFIH) and Fragile foal syndrome (FFS). The genetic causes of these conditions were:
- RAPGEF5 c.2624C>A causing EFIH
- PLOD1 c.2032G>A leading to FFS
The researchers’ aim was to understand the frequency of these genetic variants in the US Thoroughbred population from 1988 to 2019.
Methodology
This research was a population allele frequency study using genomic DNA from hair and serum samples. The samples were genotyped for the EFIH and FFS. The researchers compared the allele frequencies between two cohorts, classified by year of birth (1988-2000, n = 728) and (2001-2019, n = 1059), and across the seven geographical regions of the United States. The frequency comparison was performed using Fisher’s Exact tests.
Findings
It was found that both EFIH and FFS allele frequencies did not vary significantly between the two time points observed. No EFIH or FFS homozygotes were detected. However, a sample from 1992 was identified as a carrier for EFIH, and one from 1993 was recognized as an FFS carrier. Geographical changes in the distribution of carriers, for both conditions, were insignificant.
Conclusion
The analysis concluded that EFIH and FFS variants are present but at a low frequency in the United States Thoroughbred population, meaning that these are not recent mutations. The study found no evidence of changes in allele frequency over time. However, due to the closed studbook and breeding practices, it is recommended to continue monitoring breed allele frequencies and genetic testing. This will help circumvent the mating of carriers and the production of affected foals.
Cite This Article
APA
Elcombe ME, Bellone RR, Magdesian KG, Finno CJ.
(2022).
Prevalence of the RAPGEF5 c.2624C>A and PLOD1 c.2032G>A variants associated with equine familial isolated hypoparathyroidism and fragile foal syndrome in the US Thoroughbred population (1988-2019).
Equine Vet J, 55(4), 666-671.
https://doi.org/10.1111/evj.13883 Publication
Researcher Affiliations
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
MeSH Terms
- Animals
- Horses / genetics
- Prevalence
- Genotype
- Alleles
- Reproduction
- Syndrome
- Hypoparathyroidism / genetics
- Hypoparathyroidism / veterinary
- Horse Diseases / epidemiology
- Horse Diseases / genetics
Grant Funding
- L40 TR001136 / NCATS NIH HHS
- 5T35OD010956-22 / NIH Office of the Director
- UC Davis Veterinary Genetics Laboratory
- UC Davis Center for Equine Health
Conflict of Interest Statement
Competing interests. M.E. Elcombe and R.R. Bellone are affiliated with the UC Davis Veterinary Genetics Laboratory, which provides genetic diagnostic tests in horses and other species including testing for the EFIH and FFS mutations described in this manuscript. C.J. Finno and K.G. Magdesian have no competing interests.
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