This study provides crucial insights into the transcriptomic and genomic landscape of both infected and uninfected cattle revealing key genes, lncRNAs and SNPs associated with the disease condition. By identifying DEGs and potential biomarkers linked to MAP infection, the study offers valuable contributions to disease management and molecular understanding. These markers hold promise for integration into breeding programs facilitating the selection of cattle with increased resistance to MAP infection.
The study began with the meticulous phenotyping of control and clinically infected animals employing specific inclusion and exclusion criteria. The infected group exhibited distinct characteristics, including positive Zn staining, loose faeces and a low body condition score. while the healthy or control group maintained good health throughout the monitoring period. A total of 42 animals from the healthy and infected groups under went RNASeq for genome wide identification of expressed transcripts. Analysis revealed 1905 significantly deferentially expressed genes in the infected group with 1588 up regulated and 317 down regulated genes, Additionally the study identified 58621 lncRNA transcripts in cattle samples featuring 11042 single exon lncRNAs. Analysis of these lncRNAs pinpointed 3123 differentially expressed lncRNA genes with 2459 upregulated and 664 downregulated in the diseased condition. Coexpression modules were constructed using 1905 DEmRNAs and 3123 DElncRNAs resulting in 11 modules, The turquoise module showed significant positive correlations with diseased condition, Zn staining and fecal condition while negatively correlating with body condition scoring. This module emerged as the most valuable and pathway enrichment uncovered pathways related to response to external stimuli, immune system processes,   defence response, cell differentiation and cell surface receptor signalling pathways. Protein-Protein Interaction analysis of module genes identified several crucial genes including IL7R, SELL, TLR4, KLRK1, IFNG, TGFB1, CD68, CXCR6, GZMB, KLRG1, MMP9, GZMA. To conduct Genome Wide Association Studies between the diseased and healthy groups the genomes of 16 disease and 18 healthy animals were sequenced. Sequence data analysis identified a comprehensive set of 38530512 variants of which 29858713 were determined to be bi-allelic and considered suitable for association analysis. The association analysis was performed using a Mixed Linear Model revealing some major SNPs with a significant association with the healthy and disease condition after Bonferroni correction. These SNPs have connections to proteins associated with Axon guidance, Platelet activation and the Rap1 signalling pathway. Furthermore the KEGG database uncovered endocytosis pathways involving the associated genes.