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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Genomics and Improvement Laboratory » Research » Publications at this Location » Publication #418646
Research Project: Increasing Accuracy of Genomic Prediction, Developing Algorithms, Selecting Markers, and Evaluating New Traits to Improve Dairy Cattle

Location: Animal Genomics and Improvement Laboratory

Title: Validation of loci and genes associated with fertility in Holstein cows using gene-set enrichment analysis-SNP and genotype-by-sequencing

Author
item KISER, JENNIFER - Washington State University
item SEABURY, CHRISTOPHER - Texas A&M University
item Neupane, Mahesh
item MORAES, JOAO - Oklahoma State University
item HERRICK, ALLISON - Washington State University
item DALTON, JOSEPH - University Of Idaho
item BURNS, GREGORY - Michigan State University
item SPENCER, THOMAS - University Of Michigan
item NEIBERGS, HOLLY - Washington State University

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/13/2025
Publication Date: 2/21/2025
Citation: Kiser, J.N., Seabury, C.M., Neupane, M., Moraes, J.G., Herrick, A.L., Dalton, J., Burns, G., Spencer, T.E., Neibergs, H. 2025. Validation of loci and genes associated with fertility in Holstein cows using gene-set enrichment analysis-SNP and genotype-by-sequencing. BMC Genomics. 26. Article e174. https://doi.org/10.1186/s12864-025-11364-9.
DOI: https://doi.org/10.1186/s12864-025-11364-9

Interpretive Summary: Revenues from dairy cattle products account for roughly 21.3% ($41.8 billion) of all animal cash receipts within the United States. Prior to lactation and the generation of dairy products, cattle must first conceive and maintain the pregnancy through the normal gestation period, making fertility critical in a profitable dairy. The financial effect of pregnancy loss in dairy cattle is substantial, with over $7 billion in lost revenue accrued annually due to a relatively low cow conception rate. Despite better management and new technologies, current average cow pregnancy rate is only 36% for U.S. dairy cows. In this study, we identified important genes and biological mechanisms associated with pregnancy loss in cows. These findings can be incorporated into current commercial products to help maintain pregnancies in cattle. This would decrease financial losses for farmers due to failed pregnancies and increase their production and efficiency.

Technical Abstract: Background: The financial strain fertility issues cause the dairy cattle is substantial, with over $7 billion in lost revenue accrued annually due to a relatively low cow conception rate (CCR; 36%) for US dairy cows. While CCR has been improving through genomic selection, identification of causal mutations would help improve the rate of genetic progress with genomic selection and provide a better understanding of infertility. The objectives of this study were to: 1) identify genes and gene-sets associated with CCR to the first breeding (CCR1) and the number of breedings required to conceive (TBRD) in Holstein cows and 2) identify putative functional variants associated with CCR1 and TBRD through a custom genotype-by-sequencing array. The study consisted of 1064 cows (495 pregnant to first breeding, 497 pregnant to subsequent [2-20] services, and 72 that never conceived). Cows were artificially inseminated, and pregnancy was determined 35d post breeding by rectal palpation. Gene-set enrichment analyses with SNP data (GSEA-SNP) were conducted for CCR1 and TBRD with a normalized enrichment score (NES) >= 3.0 required for significance. Leading edge genes (LEG) and positional candidate genes from this and 26 additional studies were used to validate 100 loci associated (P < 1 × 10-5) with cow fertility using a custom sequencing genotyping array of putative functional variants (exons, promoters, splice sites and conserved regions). Results: GSEA-SNP identified 95 gene-sets (1,473 LEG) enriched for CCR1 and 67 gene sets enriched (1,438 LEG) for TBRD (NES >= 3). Thirty-four gene-sets were shared between CCR1 and TBRD along with 788 LEG. The association analysis for TBRD identified three loci: BTA1 at 83 Mb, BTA1 at 145 Mb and BTA 20 at 46 Mb (P < 1 × 10-5). The three loci associated with TBRD contained candidate genes with functions relating to implantation and uterine receptivity. No loci were associated with CCR1, however a single locus on BTA1 at 146 Mb (also identified in TBRD) trended toward significance with an (FDR=0.04). Conclusions: The validation of three loci associated with CCR and TBRD in Holsteins can be used to improve fertility through genomic selection and provide insight into understanding infertility.