Identification of key gene networks and pathways associated with sole ulcers in lactating dairy cows

Document Type


Publication Date



American Dairy Science Association


Journal of Dairy Science




Suppl. 1






RNA-seq, lameness, sole ulcer


This study aimed to evaluate the transcriptomic profile of the corium tissue of lactating dairy cows experiencing sole ulcers disease. Multipa- rous Holstein dairy cows clinically healthy or diagnosed with sole ulcers (n = 7/group) were selected for the hoof biopsy procedure. Hoof samples were collected under local anesthesia from the sole of the hoof in claw zone 4. All RNA samples were sequenced using Illumina, NovaSeq S4 at the University of Minnesota Genomics Center. Principal component analysis (PCA) and ANOVA for each gene was calculated using the DESeq2 package in R to determine the differentially expressed (DE) genes, fold-change (FC), and P-value based on the comparison of sole ulcer (SU) over healthy cows (HC). The DE genes with at least ± 2-fold change were retained for an enrichment pathway analysis using gene ontology (GO) terms and the enrichGO function in the Clusterprofiler package in R. The FDR cut-off value was set to <0.01. The PCA analysis clearly discriminated the hoof transcriptomes between HC and SU cows. The number of DE genes in SU and HC was 10,274 ± 21.6 and 10,289 ± 36.4 (mean ± SD), respectively. Several genes coding for keratins (e.g., KRT34 and KRT85) were downregulated (FC < −15) in SU cows, while the highest upregulated (FC = 10.9) gene in SU was IL6. The GO analysis showed significant downregulation of GO terms in SU cows compared with HC in the Cellular Component category, including inter- mediate and keratin filaments, and intermediate filament cytoskeleton. Upregulated genes in SU cows resulted in a significant enrichment of GO terms in the Biological Process category, including extracellular matrix organization and vasculature development, as well as GO terms in the Cellular Component category such as extracellular matrix and cell surface. The GO terms enrichment across biological process, cellular components, and molecular function categories were highly involved in the keratinization process, inflammation, and transcriptional regulation. These processes are crucial for the development of sole ulcers causing lameness in dairy cows. This study provides an in-depth molecular and functional foundation for future nutritional interventions to reduce sole ulcer incidence in dairy herds.

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