Genetic analysis of the blood transcriptome of young healthy pigs to improve disease resilience

Abstract

Disease resilience is the ability of an animal to maintain productive performance under disease conditions and is an important selection target. In pig breeding programs, disease resilience must be evaluated on selection candidates without exposing them to disease. To identify potential genetic indicators for disease resilience that can be measured on selection candidates, we focused on the blood transcriptome of 1594 young healthy pigs with subsequent records on disease resilience. Transcriptome data were obtained by 3’mRNA sequencing and genotype data were from a 650 K genotyping array. Heritabilities of the expression of 16,545 genes were estimated, of which 5665 genes showed significant estimates of heritability (p < 0.05), ranging from 0.05 to 0.90, with or without accounting for white blood cell composition. Genes with heritable expression levels were spread across chromosomes, but were enriched in the swine leukocyte antigen region (average estimate > 0.2). The correlation of heritability estimates with the corresponding estimates obtained for genes expressed in human blood was weak but a sizable number of genes with heritable expression levels overlapped. Genes with heritable expression levels were significantly enriched for biological processes such as cell activation, immune system process, stress response, and leukocyte activation, and were involved in various disease annotations such as RNA virus infection, including SARS-Cov2, as well as liver disease, and inflammation. To estimate genetic correlations with disease resilience, 3205 genotyped pigs, including the 1594 pigs with transcriptome data, were evaluated for disease resilience following their exposure to a natural polymicrobial disease challenge. Significant genetic correlations (p < 0.05) were observed with all resilience phenotypes, although few exceeded expected false discovery rates. Enrichment analysis of genes ranked by estimates of genetic correlations with resilience phenotypes revealed significance for biological processes such as regulation of cytokines, including interleukins and interferons, and chaperone mediated protein folding. These results suggest that expression levels in the blood of young healthy pigs for genes in biological pathways related to immunity and endoplasmic reticulum stress have potential to be used as genetic indicator traits to select for disease resilience.