Thoroughbred stallion fertility is significantly associated with FKBP6 genotype but not with inbreeding or the contribution of a leading sire.
Abstract: This is a follow-up study to validate the previously detected association of the FKBP6 gene with stallion subfertility. Using a select cohort of 150 Thoroughbred stallions with detailed breeding records, we confirm significant association (P < 0.0001) between low per-cycle pregnancy rates (≤50%) and a combined A/A-A/A genotype of SNPs chr13:11 353 372G>A and chr13:11 353 436A>C in FKBP6 exon 5. We also show that stallion subfertility and the combined genotype A/A-A/A are not associated with the level of genetic diversity based on 12 autosomal microsatellite markers, or with pedigree-based inbreeding rate, or the extent of contribution of a leading Thoroughbred sire, Northern Dancer, in a stallion's pedigree. We develop a TaqMan allelic discrimination assay for the two SNPs to facilitate accurate and high-throughput genotyping. We determine allele, genotype and combined genotype frequencies of FKBP6 exon 5 SNPs in a global cohort of 518 Thoroughbreds (76% stallions or geldings and 24% mares) and show that the frequency of the A/A-A/A genotype is 4%. Because there is no similar association between the FKBP6 exon 5 genotype and stallion subfertility in Hanoverians, we suggest that the two SNPs are not causative but rather tagging a breed-specific haplotype with genetic variants unique to Thoroughbreds. Further WGS-based research is needed to identify the molecular causes underlying the observed genotype-phenotype association in Thoroughbred stallions.
© 2021 Stichting International Foundation for Animal Genetics.
Publication Date: 2021-10-05 PubMed ID: 34610162DOI: 10.1111/age.13142Google Scholar: Lookup
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Summary
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This research investigates the association between the FKBP6 gene and subfertility in Thoroughbred stallions. The study shows a significant connection between a specific genotype and lower pregnancy rates but finds no association with inbreeding, genetic diversity, or lineage from a notable sire.
FKBP6 Genotype and Stallion Fertility
- Researchers carried out a follow-up study to establish the relationship between the FKBP6 gene and stallion subfertility, a topic that had been detected in previous research.
- The study involved 150 Thoroughbred stallions, all with detailed breeding records.
- The primary finding was a significant relationship between low pregnancy rates per cycle (≤50%) and a specific genotype (A/A-A/A) of two Single Nucleotide Polymorphisms (SNPs) located in exon 5 of the FKBP6 gene.
- The association was found to be remarkably significant (P < 0.0001), highlighting that this genetic factor might affect stallion fertility.
No Association with Inbreeding or Lineage
- The research also examined possible associations with genetic diversity, inbreeding rates, or the influence of a prominent Thoroughbred sire lineage (Northern Dancer).
- No correlation was found between these factors and stallion subfertility or the identified A/A-A/A genotype.
- These results suggest that subfertility in these stallions does not relate to a decrease in genetic diversity or a higher rate of inbreeding.
The FKBP6 Genotype Frequency
- The researchers developed an efficient method for genotyping the two SNPs associated with subfertility, thereby aiding accurate and high-throughput genotyping in stallions.
- The frequency of the A/A-A/A genotype was determined to be approximately 4% in a global sample of 518 Thoroughbreds.
- However, no such association was found in Hanoverians, a different breed of horse. This distinction suggests that the identified SNPs may not directly cause subfertility, but instead may be markers of a breed-specific haplotype in Thoroughbreds.
Further Research Needed
- The study calls for further Whole Genome Sequencing (WGS) based research to determine the molecular causes underlying the detected genotype-phenotype association in Thoroughbred stallions.
- Identifying these causes would enhance understanding of stallion subfertility, guide breeding strategies, and potentially lead to novel therapeutic approaches.
Cite This Article
APA
Castaneda C, Juras R, Kjöllerström J, Hernandez Aviles C, Teague SR, Love CC, Cothran EG, Varner DD, Raudsepp T.
(2021).
Thoroughbred stallion fertility is significantly associated with FKBP6 genotype but not with inbreeding or the contribution of a leading sire.
Anim Genet, 52(6), 813-823.
https://doi.org/10.1111/age.13142 Publication
Researcher Affiliations
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
MeSH Terms
- Animals
- Fertility / genetics
- Horses / genetics
- Horses / physiology
- Inbreeding
- Male
- Tacrolimus Binding Proteins / genetics
- Tacrolimus Binding Proteins / metabolism
Grant Funding
- Legends Premier Stallion Season Auction
- Texas A&M Molecular Cytogenetics and Animal Genetics Services
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Citations
This article has been cited 5 times.- Bailey E, Finno CJ, Cullen JN, Kalbfleisch T, Petersen JL. Analyses of whole-genome sequences from 185 North American Thoroughbred horses, spanning 5 generations. Sci Rep 2024 Oct 2;14(1):22930.
- Hernández-Avilés C, Ramírez-Agámez L, Weintraub ST, Scoggin CF, Davis BW, Raudsepp T, Varner DD, Love CC. Proteomic analysis of sperm from fertile stallions and subfertile stallions due to impaired acrosomal exocytosis. Sci Rep 2024 May 30;14(1):12446.
- Medica AJ, Lambourne S, Aitken RJ. Predicting the Outcome of Equine Artificial Inseminations Using Chilled Semen. Animals (Basel) 2023 Mar 30;13(7).
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