The aim of this work package was to quantify the genetic contribution to host susceptibility or resistance, identify genome regions contributing to host resistance, and evaluate different strategies to improve host resistance.
Evidence from experimental and field studies indicates a significant effect of host genetics on the outcome of lumpy skin disease virus (LSDV) infection. In order to identify host genes involved in resistance to LSD clinical cases, matched controls were sourced from archived experimental samples and from outbreaks in consortium partner countries. We collected DNA information and clinical data from 500 infected animals (cases) and matched these with 500 animals from the same farms that did not succumb to LSD (controls). We then carried out a genome-wide association study (GWAS) to identify genetic loci underlying susceptibility/resistance to LSD. The cattle were genotyped and quantitative trait loci identified.
The GWAS study was complemented by two gene expression studies that compared the expression levels of animals that became clinically ill after artificial infection with those that did not become ill. This showed that, while there were very clear gene expression differences between animals depending on disease outcome these difference were also quite specific for different LSDV strains.
On the basis of the regions that were identified and the overall genetic parameters for susceptibility/resistance to LSD, we did some computer simulations to evaluate different breeding strategies to improve LSD resistance. We used DNA information to select for favourable gene variants (alleles) at either a few loci (Marker Assisted Selection) or the whole genome (Genomic Selection). Focusing on a marker assisted selection scenario based on the GWAS results we saw that relatively fast improvement in disease resistance could be achieved if resistance was given priority as the main breeding goal.
We also studied gene expression in pigs infected with African swine fever with different disease outcomes. The differentially expressed genes included even one gene with sequence variation that differentiated between disease outcome in immunized pigs.