Genomic partition of inbreeding depression in production traits of U.S. Jersey cattle using functional annotations

Authors: XU, CHANG - North Carolina State University; MALTECCA, CHRISTIAN - North Carolina State University; TIEZZI, FRANCESCO - North Carolina State University; COLE, JOHN - North Carolina State University; Toghiani, Sajjad; MA, LI - University Of Maryland; JIANG, JICAI - North Carolina State University

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/28/2025
Publication Date: 10/1/2025
Citation: Xu, C., Maltecca, C., Tiezzi, F., Cole, J.B., Toghiani, S., Ma, L., Jiang, J. 2025. Genomic partition of inbreeding depression in production traits of US Jersey cattle using functional annotations. Journal of Dairy Science. 108(10):11254-11268. https://doi.org/10.3168/jds.2025-26738.
DOI: https://doi.org/10.3168/jds.2025-26738

Interpretive Summary: Inbreeding depression results in reduced survival, production, and reproduction traits in different populations, including dairy cattle. Despite efforts to quantify this decline, the genetic and molecular causes of these effects, especially in dairy cattle, remain unclear. Our research showed that specific parts of the dairy cow's genetic makeup, like certain regions that control gene activity, have a big impact on how negative effects of inbreeding affect traits such as milk, protein, and fat yield. Through the utilization of advanced genetic models, the impact of inbreeding on these traits in a large population of Jersey cows was identified. Our findings highlight how certain genetic areas make inbreeding more harmful for dairy cows. This knowledge has the potential to lead to improved breeding strategies for genomic selection, ultimately benefiting dairy producers, consumers, and the industry overall. By better understanding the genetic and molecular mechanisms behind inbreeding depression, the study opens doors for more effective strategies to mitigate these effects and enhance dairy cattle breeding practices. This investigation not only contributes to the agricultural sector but also advances scientific understanding of inbreeding depression, offering valuable insights for future research and application in the field of animal genetics and breeding.

Technical Abstract: Inbreeding depression (InD) refers to the mean reduction in trait values due to inbreeding, with detrimental effects on survival, production, and reproduction traits that have been observed in many natural and domesticated populations. Despite efforts to measure how much reduction in the traits of interest was caused by InD, the genetic and molecular basis of these declines remains unclear, particularly in dairy cattle. In this research, we used a linear mixed model to partition the InD of three production traits in 245,517 genotyped Jersey cows from the Council on Dairy Cattle Breeding (CDCB; Bowie, MD, USA) database. We mapped 9,532,696 imputed sequence variants into five functional annotation categories (i.e., intron, promoter, Genomic Evolutionary Rate Profiling (GERP) constrained elements, coding sequence (CDS), untranslated regions (UTR), and remaining). We estimated the effects of InD attributed to each functional annotation category by a mixed-model method accounting for additive effects and relatedness through a genomic relationship matrix (GRM). The InD for milk yield was significantly enriched for promoter regions (enrichment ratio Rk =20.1, SE=6.44), UTR regions (Rk=57.96, SE=16.62) and GERP regions (Rk=35.91, SE=7.00). The enrichment ratio represents the disproportionate effect that annotation-specific homozygosity has on the trait mean compared to the magnitude of InD on the whole-genome level. Similarly, protein yield showed significant enrichment of InD for promoter regions (Rk=15.25, SE=5.45), UTR regions (Rk=46.44, SE=14.07) and GERP regions (Rk=32.73, SE=5.92), while fat yield showed significant enrichment of InD for UTR regions (Rk=40.20, SE=12.77) and GERP regions (Rk=28.72, SE=5.34). Our results indicate that certain functional annotations in dairy cattle genome are disproportionally responsible for the detrimental effects of inbreeding, which could be vulnerable to deleterious mutations. This research can help better elucidate the genetic and molecular basis of InD in dairy cattle genome, and potentially guide breeding strategies for genomic selection.