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  • Title: Thoroughbred stallion fertility is significantly associated with FKBP6 genotype but not with inbreeding or the contribution of a leading sire.
    Author: Castaneda C, Juras R, Kjöllerström J, Hernandez Aviles C, Teague SR, Love CC, Cothran EG, Varner DD, Raudsepp T.
    Journal: Anim Genet; 2021 Dec; 52(6):813-823. PubMed ID: 34610162.
    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.
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