High-density genome-wide association study points out major candidate genes for resistance to infectious pancreatic...

This study focuses on genetic resistance to infectious pancreatic necrosis (IPN), a highly contagious disease caused by an aquatic birnavirus (IPNV) which especially affects salmonids worldwide. The objectives were to estimate the heritability of IPN resistance and to fine map quantitative trait loci (QTL) using a Bayesian Sparse Linear Mixed Model to identify candidate genes possibly linked to IPN resistance in two successive generations from a French commercial strain of rainbow trout. For each generation, 2000 fish were experimentally exposed by bath to IPNV and mortalities were monitored daily during 5 weeks. All fish were genotyped using a medium-density 57 K single nucleotide polymorphism (SNP) chip and imputed to high-density genotypes (665 K SNPs).

The mean survival rate was 70% after 37 days, with a higher survival rate in the second generation compared to the first one (78% versus 61%). Heritability was moderate (~ 0.20). Approximately 74% of the genetic variance of IPN resistance was explained by several tens of SNPs. In total, 25 QTL were mapped on 10 chromosomes, of which 7 were detected with very strong evidence, on chromosomes 1, 14, 16 and 28. The most interesting QTL were associated to top SNPs with mean survival rate differences over 20% between the beneficial and detrimental homozygous genotypes. Those SNPs were all located within promising functional candidate genes on chromosome 1 (uts2d, rc3h1, ga45b) and chromosome 16 (irf2bp, eif2ak2), which were all associated with regulation of inflammatory pathways. A key factor for the genetic differences in susceptibility to IPNV among fish is the dsRNA-dependent serine/threonine-protein kinase (PKR) encoded by the eif2ak2 gene.

All genes associated with the most significant QTL on chromosomes 1 and 16 are involved in the regulation of inflammatory pathways, strongly suggesting a central role of inflammation in IPN resistance in rainbow trout. These findings offer the possibility of marker-assisted selection for rapid dissemination of genetic improvement for IPN resistance.