Gene function & annotation

Uncovering recessive fertility disorders in dairy cattle populations using large-scale genomic and phenotypic data

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Abstract

Reproductive performance is a key determinant of cattle herd management, influencing both the onset of lactation and the production of calves for market or replacement. Over the past 80 years, female fertility has declined markedly, particularly in intensive breeds, a trend generally attributed to breeding strategies historically focused on production traits. However, the role of hidden recessive genetic defects in this decline remains unexplored. Here, we analyzed life-history and reproductive records (including dates of birth, insemination, calving, and death) from over one million Montbéliarde, Normande, and Brown Swiss females genotyped with the Illumina EuroGMD array, with genotype data also available for their ancestors.Applying the Homozygous Haplotype Enrichment/Depletion (HHED) method to repeat breeders (≥3 unsuccessful inseminations) and females conceiving at first insemination, we identified 13 significant recessive loci in heifers and first-parity cows across breeds. By mining whole-genome sequences of 1,869 cattle, we pinpointed ten strong candidate variants with haplotype x genotype correlation R² > 0.5 and damaging predicted consequences on proteins (ASCC2, CCDC57, CCDC61, CRISP1, DEPDC7, GFER, LCORL, OVGP1, PIK3C3, TDRD12). Among these, only OVGP1 has a known role in female fertility in mammals, while others influence male fertility or affect key biological functions for reproductive success. We also estimated the effects of these haplotypes across the entire genotyped female population for forty traits, adjusting for environmental factors. For all loci, homozygous individuals exhibited strong reductions in fertility compared with wild-type animals, with effects often ranging from 2 to 4 genetic standard deviations (GSD). Several loci also significantly affected production or morphological traits in homozygous females, although with smaller effect sizes (typically around 0.25 GSD).Finally, we analyzed multiple ovulation and embryo transfer data for the most significant locus in each breed (B17.67-ASCC2, M3.31-OVGP1, and N19.50-CCDC57). The average number of structures (embryos or unfertilized oocytes) collected was similar between homozygous and wild-type donors. However, their nature, quality, and/or developmental success to calving following transfer to wild-type recipient dams differed significantly depending on the locus. In contrast, homozygous females used as recipient dams receiving wild-type embryos exhibited normal conception rates, indicating that overall reproductive physiology is intact and that defects are restricted to gametes and early embryonic development.In conclusion, our study demonstrates the existence of previously overlooked recessive loci that impair female fertility in dairy cattle. Accounting for these loci in breeding programs could tangibly improve reproductive performance, enhance breeders' outcomes, and reduce the environmental footprint of the dairy sector. These findings also provide promising avenues for discovering novel genes involved in human infertility, a major global health challenge, leveraging the bovine model.

Keywords: 2026

How to Cite:

Jourdain, J., Besnard, F., Barbat, A., Boussaha, M., Fritz, S., Chambrial, M., Fayolle, G., Gamarra Lacaze, G., Lacaze, S., Schibler, L., Dutheil, L., Foucras, G., Boichard, D. & Capitan, A., (2026) “Uncovering recessive fertility disorders in dairy cattle populations using large-scale genomic and phenotypic data”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2286646. doi: https://doi.org/10.31274/wcgalp.24077

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