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Animal genetics2021; 52(6); 813-823; doi: 10.1111/age.13142

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.
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Publication Date: 2021-10-05 PubMed ID: 34610162DOI: 10.1111/age.13142Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

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

Animal genetics
ISSN: 1365-2052
NlmUniqueID: 8605704
Country: England
Language: English
Volume: 52
Issue: 6
Pages: 813-823

Researcher Affiliations

Castaneda, C
  • Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
Juras, R
  • Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
Kjöllerström, J
  • Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
Hernandez Aviles, C
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
Teague, S R
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
Love, C C
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
Cothran, E G
  • Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
Varner, D D
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
Raudsepp, T
  • 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

References

This article includes 31 references
  1. Belkhir K, Borsa P, Chikhi L, Raufaste N, Bonhomme F. GENETIX 4.05, Logiciel Sous Windows TM Pour la Génétique des Populations. .
  2. Blanchard TL, Varner DD. Evaluating breeding soundness in stallions. 5. Predicting potential fertility. Veterinary Medicine 1997 92, 815-8.
  3. Brinsko SP, Blanchard TL, Varner DD, Schumacher J, Love CC, Hinrichs K, Hartman DL. Manual of Equine Reproduction, 3rd edn. 2011.
  4. Brinsko SP, Love CC, Bauer JE, Macpherson ML, Varner DD. Cholesterol-to-phospholipid ratio in whole sperm and seminal plasma from fertile stallions and stallions with unexplained subfertility. Animal Reproduction Science 2007 99, 65-71.
  5. Carrell DT. The genetics of male infertility in the era of genomics. 2007 pp. 3-27.
  6. Colenbrander B, Gadella BM, Stout TAE. The predictive value of semen analysis in the evaluation of stallion fertility. Reproduction in Domestic Animals 2003 38, 305-11.
  7. Cosenza M, La Rosa V, Rosati R, Chlofalo V. Genetic diversity of the Italian thoroughbred horse population. Italian Journal of Animal Science 2019 18, 538-45.
  8. Das PJ, Lyle SK, Beehand D, Chowdhary BP, Raudsepp T. Cytogenetic and molecular characterization of Y isochromosome in a 63XO/64Xi(Yq) mosaic karyotype of an intersex horse. Sexual Development 2012 6, 117-27.
  9. Fawcett JA, Sato F, Sakamoto T, Iwasaki WM, Tozaki T, Innan H. Genome-wide SNP analysis of Japanese Thoroughbred racehorses. PLoS One 2019 14, e0218407.
  10. Garbe JR, Da Y. A software tool for the graphical visualization of large and complex populations. Yi Chuan Xue Bao 2003 30, 1193-5.
  11. Griffin RA, Baker M, Aitken RJ, Swegen A, Gibb Z. What makes a fertile sperm? Unique molecular attributes of stallion fertility. Reproduction 2019 158, R125-37.
  12. . Principal Rules and Requirements of the American Stud Book. 2020.
  13. Juras R, Cothran EG, Klimas R. Genetic analysis of three Lithuanian native horse breeds. Acta Agriculturae Scandinavica, Section A - Animal Science 2003 53, 180-5.
  14. Kalashnikov V, Khrabrova L, Blohina N, Zaitcev A, Kalashnikova T. Dynamics of the inbreeding coefficient and homozygosity in thoroughbred horses in Russia. Animals 2020 10, 1217.
  15. Kalbfleisch TS, Rice ES, DePriest MS. Improved reference genome for the domestic horse increases assembly contiguity and composition. Communications Biology 2018 1, 197.
  16. Khanshour A, Juras R, Blackburn R, Cothran EG. The legend of the Canadian horse: genetic diversity and breed origin. Journal of Heredity 2015 106, 37-44.
  17. Leeb T. The horse genome project-seqeunce based insights into male reproducive mechanisms. Reproduction in Domestic Animals 2007 42, 45-50.
  18. Leeb T, Sieme H, Topfer-Petersen E. Genetic markers for stallion fertility-lessons from humans and mice. Animal Reproduction Science 2005 89, 21-9.
  19. Love CC. Relationship between sperm motility, morphology and the fertility of stallions. Theriogenology 2011 76, 547-77.
  20. Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nature Medicine 2008 14, 1197-213.
  21. McGivney BA, Han H, Corduff LR, Katz LM, Tozaki T, MacHugh DE, Hill EW. Genomic inbreeding trends, influential sire lines and selection in the global Thoroughbred horse population. Scientific Reports 2020 10, 466.
  22. Peakall R, Smouse PE. GenAlEx 6.5: genetic analysis in Excel. Population genetic software for teaching and research-an update. Bioinformatics 2012 28, 2537-9.
  23. Raudsepp T. Genetics of equine reproductive diseases. Veterinary Clinics of North America-Equine Practice 2020 36, 395-409.
  24. Raudsepp T, Chowdhary BP. Chromosome aberrations and fertility disorders in domestic animals. Annual Review of Animal Biosciences 2016 4, 15-43.
  25. Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era. Animal Genetics 2019 50, 569-97.
  26. Raudsepp T, McCue ME, Das PJ. Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions. PLoS Genetics 2012 8, e1003139.
  27. Ruiz AJ, Castaneda C, Raudsepp T, Tibary A. Azoospermia and Y chromosome-autosome translocation in a Friesian stallion. Journal of Equine Veterinary Science 2019 82, 102781.
  28. Schrimpf R, Metzger J, Martinsson G, Sieme H, Distl O. Implication of FKBP6 for male fertility in horses. Reproduction in Domestic Animals 2015 50, 195-9.
  29. Todd ET, Hamilton NA, Velie BD, Thomson PC. The effects of inbreeding on covering success, gestation length and foal sex ration in Australian thoroughbred horses. BMC Genetics 2020 21, 41.
  30. Varner DD, Blanchard TL, Brinsko SP, Love CC, Taylor TS, Johnson L. Techniques for evaluating selected reproductive disorders of stallions. Animal Reproduction Science 2000 60-61, 493-509.
  31. Wade CM, Giulotto E, Sigurdsson S. Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 2009 326, 865-7.

Citations

This article has been cited 5 times.
  1. 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.
    doi: 10.1038/s41598-024-73645-9pubmed: 39358442google scholar: lookup
  2. 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.
    doi: 10.1038/s41598-024-63410-3pubmed: 38816557google scholar: lookup
  3. Medica AJ, Lambourne S, Aitken RJ. Predicting the Outcome of Equine Artificial Inseminations Using Chilled Semen. Animals (Basel) 2023 Mar 30;13(7).
    doi: 10.3390/ani13071203pubmed: 37048459google scholar: lookup
  4. Harris IT, Maddock C, Farnworth M, Nankervis K, Perrett J, Pyatt AZ, Blanchard RN. Temporal trends in equine sperm progressive motility: a systematic review and meta-regression. Reproduction 2023 Jun 1;165(6):M1-M10.
    doi: 10.1530/REP-22-0490pubmed: 37000597google scholar: lookup
  5. Aitken RJ, Lambourne S, Medica AJ. Predicting the outcome of Thoroughbred stallion matings on the basis of dismount semen sample analyses. Reproduction 2023 Mar 1;165(3):281-288.
    doi: 10.1530/REP-22-0309pubmed: 36538652google scholar: lookup
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