Exploring genetic resistance to infectious salmon anaemia virus in Atlantic salmon by genome-wide association and RNA sequencing

Abstract

Abstract Background Infectious Salmonid Anaemia Virus (ISAV) causes a notifiable disease that poses a large threat for Atlantic salmon (Salmo salar) aquaculture worldwide. There is no fully effective treatment or vaccine, and therefore selective breeding to increase resistance to ISAV is a promising avenue for disease prevention. Genomic selection and potentially genome editing can be applied to enhance host resistance, and these approaches benefit from improved knowledge of the genetic and functional basis of the target trait. The aim of this study was to characterise the genetic architecture of resistance to ISAV in a commercial Atlantic salmon population and study its underlying functional genomic basis using RNA Sequencing. Results A total of 2833 Atlantic salmon parr belonging to 194 families were exposed to ISAV in a cohabitation challenge in which cumulative mortality reached 63% over 55 days. A total of 1353 animals were genotyped using a 55 K SNP array, and the estimate of heritability for the trait of binary survival was 0.13–0.33 (pedigree-genomic). A genome-wide association analysis confirmed that resistance to ISAV was a polygenic trait, albeit a genomic region in chromosome Ssa13 was significantly associated with resistance and explained 3% of the genetic variance. RNA sequencing of the heart of 16 infected (7 and 14 days post infection) and 8 control fish highlighted 4927 and 2437 differentially expressed genes at 7 and 14 days post infection respectively. The complement and coagulation pathway was down-regulated in infected fish, while several metabolic pathways were up-regulated. The interferon pathway showed little evidence of up-regulation at 7 days post infection but was mildly activated at 14 days, suggesting a potential crosstalk between host and virus. Comparison of the transcriptomic response of fish with high and low breeding values for resistance highlighted TRIM25 as being up-regulated in resistant fish. Conclusions ISAV resistance shows moderate heritability with a polygenic architecture, but a significant QTL was detected on chromosome 13. A mild up-regulation of the interferon pathway characterises the response to the virus in heart samples from this population of Atlantic salmon, and candidate genes showing differential expression between samples with high and low breeding values for resistance were identified.

Keywords

• Disease resistance
• RNA-Seq
• Fish
• Aquaculture
• Salmo salar
• TRIM25