Towards the casual factors underlying the genetic resistance of atlantic salmon to infectious disease

The sustainable production of fish through aquaculture faces a serious and persistent threat due to infectious disease outbreaks. Of particular relevance to the UK is the impact on Atlantic salmon of viral disease such as Infectious Pancreatic Necrosis (IPN) and Pancreas Disease (PD). For both these diseases, we see clear genetic differences between fish in their resistance, which can be exploited to reduce the incidence of disease, and its impact on production. The overall aim of this research is to use novel approaches to gain an understanding of host genetic resistance, focusing on the exemplar of a major locus underlying resistance to IPN.

IPN is known to impact at two distinct windows of the salmon lifecycle; firstly in freshwater shortly after hatching, and secondly shortly after transfer to seawater. Our previous research has demonstrated that the genetic resistance to IPN across both windows of susceptibility is under the control of a single region of the genome (QTL). We have also begun to unravel the important genes and pathways underlying this QTL effect, through gene expression studies of disease-challenged fish of different genotypes.

The rapid development of 'next-generation' sequencing technology offers novel opportunities to move towards locating and understanding the causal factors underlying this QTL. In doing so, the research will significantly advance our understanding of the salmon genome, and lead to advances in the fundamental understanding of disease resistance, providing an example of a hypothesised single mutation in the host genome with dramatically altered disease consequences.

To achieve these goals, the proposed research will focus on creating the resources required to (i) identify the genes underlying the IPN QTL effects, (ii) determine the regions of the genome that affect resistance to PD, and (iii) to gain further understanding of the salmon genome and its inheritance. Firstly, a novel application of high-throughput DNA sequencing will be applied to fish of known QTL genotype to facilitate marker generation, and mapping of the QTL to a smaller region of the genome. Secondly, the gene expression profile of salmon will be characterised through cutting-edge sequencing techniques applied to genetically resistant and susceptible fish. Investigation of the genes, pathways and networks differing between the fish of alternative genotypes will yield information on the mode of action of the QTL . Thirdly, these results will be integrated through mapping relevant markers and sequences onto the salmon genome sequence. This will lead to putative functional disease resistance genes and genetic variation, which will be tested for causality. The resources generated will also be applied to map QTL underlying the resistance of salmon to PD, to investigate genetic signatures of selection in salmon, and aspects of the residual tetraploidy observed in the salmon genome.

The outcomes of the research will include advances in knowledge of the mechanisms through which disease resistance loci drastically alter the outcome of infection, with implications for the interaction of host and pathogen genomes and their evolutionary arms race. The large-scale generation of salmon sequence data will lead to an improved annotation of the genes in the forthcoming salmon genome sequence. Furthermore, elucidation of the genes underlying salmon resistance to viral disease will lead to the development of genetic tests for improved resistance, and opportunities for novel vaccines and diagnostics, which can be applied in the salmon aquaculture industry to reduce disease-related mortality. The collaboration with salmon breeding company Landcatch Natural Selection Ltd ensures a clear route for the exploitation of the results.

The sustainable production of fish through aquaculture faces a serious and persistent threat due to infectious disease outbreaks. Of particular relevance to the UK is the impact on Atlantic salmon of viral disease such as Infectious Pancreatic Necrosis (IPN) and Pancreas Disease (PD). For both these diseases, we see clear genetic differences between fish in their resistance, which can be exploited to reduce the incidence of disease, and its impact on production. The overall aim of this research is to use novel approaches to gain an understanding of host genetic resistance, focusing on the exemplar of a major locus underlying resistance to IPN.
IPN is known to impact at two distinct windows of the salmon lifecycle; firstly in freshwater shortly after hatching, and secondly shortly after transfer to seawater. Our previous research has demonstrated that the genetic resistance to IPN across both windows of susceptibility is under the control of a single region of the genome (QTL). We have also begun to unravel the important genes and pathways underlying this QTL effect, through gene expression studies of disease-challenged fish of different genotypes.
The rapid development of 'next-generation' sequencing technology offers novel opportunities to move towards locating and understanding the causal factors underlying this QTL. In doing so, the research will significantly advance our understanding of the salmon genome, and lead to advances in the fundamental understanding of disease resistance, providing an example of a hypothesised single mutation in the host genome with dramatically altered disease consequences.
To achieve these goals, the proposed research will focus on creating the resources required to (i) identify the genes underlying the IPN QTL effects, (ii) determine the regions of the genome that affect resistance to PD, and (iii) to gain further understanding of the salmon genome and its inheritance. Firstly, a novel application of high-throughput DNA sequencing will be applied to fish of known QTL genotype to facilitate marker generation, and mapping of the QTL to a smaller region of the genome. Secondly, the gene expression profile of salmon will be characterised through cutting-edge sequencing techniques applied to genetically resistant and susceptible fish. Investigation of the genes, pathways and networks differing between the fish of alternative genotypes will yield information on the mode of action of the QTL . Thirdly, these results will be integrated through mapping relevant markers and sequences onto the salmon genome sequence. This will lead to putative functional disease resistance genes and genetic variation, which will be tested for causality. The resources generated will also be applied to map QTL underlying the resistance of salmon to PD, to investigate genetic signatures of selection in salmon, and aspects of the residual tetraploidy observed in the salmon genome.
The outcomes of the research will include advances in knowledge of the mechanisms through which disease resistance loci drastically alter the outcome of infection, with implications for the interaction of host and pathogen genomes and their evolutionary arms race. The large-scale generation of salmon sequence data will lead to an improved annotation of the genes in the forthcoming salmon genome sequence. Furthermore, elucidation of the genes underlying salmon resistance to viral disease will lead to the development of genetic tests for improved resistance, and opportunities for novel vaccines and diagnostics, which can be applied in the salmon aquaculture industry to reduce disease-related mortality. The collaboration with salmon breeding company Landcatch Natural Selection Ltd ensures a clear route for the exploitation of the results.

1. Genetic markers in the salmon genome generated using RAD sequencing which show a strong association with resistance to the viral disease Infectious Pancreatic Necrosis in commercial Atlantic salmon populations. These markers form the basis of a genetic test which is being applied to reduce mortality due to IPN in salmon aquaculture in the UK and now in other salmon producing countries.
2. A novel and comprehensive gene expression library (transcriptome) of Atlantic salmon fry, both challenged with the IPN virus and controls. Comparison of gene expression between resistant and susceptible fish has revealed key genes and pathways that underpin resistance of the salmon to the virus.