Reproduction

Genomic Signatures of Fetal Loss in Holstein Cattle

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Abstract

To identify cattle with genetic susceptibility for fetal loss, > 20,000 nulliparous heifers and 10,000 primiparous cows were followed from one dairy. Cattle that conceived to the first AI service and that did not experience mastitis, metritis, metabolic, respiratory disease or a lameness during gestation based on health records of the dairy were eligible for the study. After quality control, 5714 Holstein heifers that maintained a pregnancy to ≥ 260 days (controls) and 416 heifers that experienced a pregnancy loss after day 42 of gestation (cases) remained in the study. After quality control for primiparous cows, 2519 control Holstein primiparous cows and 273 cases remained in the study. Imputed genotypes of 634,321 SNPs underwent quality control resulting in 559,223 SNPs for the GWAA for heifers and 570,306 SNPs for the primiparous cows. The Efficient Mixed Model Association eXpedited (EMMAX) method in the SNP and Variation Suite v 9.1 was used for the GWAA with a significance threshold of FDR GC was 1.0, 0.98 and 1.0 in heifers and 1.0, 1.0 and 0.99 for cows for additive, dominant and recessive inheritance models, respectively, indicating that population stratification was controlled. In heifers, 16 loci were associated (FDR < 0.05) with fetal loss and 44 loci were associated (FDR < 0.05) with fetal loss in primiparous cows in the recessive model. No loci were associated with fetal loss in the additive or dominant model for heifers or cows or shared between parities. To identify genes with importance to fetal loss within a pathway, a gene set enrichment analysis using SNPs as gene proxies (GSEA-SNP) was performed. A normalized enrichment score (NES) ≥ 3.0 was used for the significance threshold for enrichment for fetal loss in heifers and primiparous cows utilizing GO, KEGG, Reactome, BioCarta, and PANTHER databases. For heifers, the KEGG B cell receptor signaling pathway was enriched (NES = 3.2) for fetal loss whereas no gene sets were enriched in primiparous cows for fetal loss. These results confirm that there are genomic hotspots that contribute to fetal loss in Holstein cattle. Ongoing work to further characterize loci associated with fetal loss include meta-analysis of multiple dairies, long read sequencing to identify putative causal variants and epigenetic marks for fetal loss. This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2023-67015-39524 from the USDA National Institute of Food and Agriculture.

Keywords: 2026

How to Cite:

Herrick, A., Issaka Salia, O., Kelson, V., Kiser, J., Murdoch, B., Neibergs, H., Stegemiller, M. & Suarez, E., (2026) “Genomic Signatures of Fetal Loss in Holstein Cattle”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2286007. doi: https://doi.org/10.31274/wcgalp.23836

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