Integration of genome and transcriptome reveals core genes and allele-specific expression genetic variants associated with immune differentiation of taurine ancestry dairy cattle from indicine ancestry cattle.

Background: Disease is a key factor to shorten productive lifespan of dairy cattle. Shifting from classical 'treating existing diseases' to 'preventing diseases before they occur' is a challenge in high-producing dairy cattle. Immunity plays a crucial role in defending against disease. Substantial evidence indicates that the immune function of taurine ancestry cattle and indicine ancestry cattle are distinct. Therefore, this study aims: (1) to identify core immune genes (CIG) and allele-specific expression (ASE) variants by comparing taurine ancestry dairy cattle with indicine ancestry cattle; and (2) to provide candidate markers for future validation and then used in genomic selection for enhanced immunity in taurine ancestry dairy cattle.

Results: Here, transcriptome and genome data generated by us from the livers and spleens of taurine ancestry dairy cattle (Holstein and Xinjiang Brown) and indicine ancestry cattle (Dehong humped and Dengchuan), along with publicly downloaded transcriptome and genome data of immune cells (monocytes, CD4 T cells, and B cells) from Holstein and Nelore were systematically analyzed. We constructed transcriptomic-based immune- and disease-scores to assess immunity between taurine ancestry dairy cattle and indicine ancestry cattle. Taurine ancestry dairy cattle exhibited lower immune-scores (T cell receptor signaling, etc.) and higher disease-scores (Staphylococcus aureus infection, etc.) compared to indicine ancestry cattle. A total of 184 CIG underlying the score differences were identified. Furthermore, we performed ASE analysis and verified the identified ASE genes and ASE SNPs by using large-scale expression quantitative trait loci (eQTLs) data from immune tissues and cells. A total of 1,255 ASE genetic variants related to the CIG were identified in this study. These variants were significantly enriched in active promoters and enhancers in the spleen. Finally, we verified the association between CIG and health traits in 27,214 Holstein bulls and 101 Holstein cows.

Conclusions: This study uses high-throughput omics data to provide new insights into the digitalization of immunity, defined as quantifying immune- and disease-related pathway activity through gene expression levels. Our study also provides candidate markers for future functional validation and genomic selection strategies aimed at enhancing immunity in Holstein cattle.