Dissecting structural and functional genomic factors underlying the resistance of atlantic salmon fry to infectious pancreatic necrosis

  • Bishop, Stephen (Principal Investigator)

Project Details

Description

This project addressed the genetic control of resistance to infectious pancreatic necrosis (IPN) in Atlantic salmon, with the ultimate aim of finding genetic solutions to this problem. In this respect we have succeeded fully, providing the salmon breeding industry with genetic markers that they now incorporate routinely into their breeding programmes. The consequence is that IPN no longer a current problem in fish that have been bred for IPN resistance. Further, identification of the causative mutation would be of fundamental interest to all scientists working on viral disease infections, pathology and resistance: a single locus effect which essentially determines whether an animal survives or dies following infection is of major interest.

The stated project aims were:
Aim 1. To demonstrate genetic variation in IPN resistance in salmon fry, and resolve this variation into QTL: Achieved fully. We have quantified the heritability of resistance to IPN and identified a single QTL which has been verified across independent populations. Further this QTL is now defined by markers in population-wide linkage disequilibrium with the causative mutation.

Aim 2. To determine genes and pathways underlying genetically determined differences in the resistance of fry to IPN: Achieved fully. We now have a consistent transcriptomic signature which is indicative of infection in resistant vs. susceptible fish, and has led to the identification of the most relevant pathways involved in IPN resistance.

Aim 3. To synthesize structural and functional genomics outputs to identify candidate quantitative trait genes: Achieved fully. Using new techniques (not foreseen at the outset of the project) we have identified SNPs which are in strong population-wide LD with the causal mutation. These data have been combined with a comparative genomic approach to identify the genomic location of orthologous genes from the pathways we identified in the microarray analyses. This has led to the identification of a single syntenic region in model fish genomes from which putative quantitative trait genes for resequencing have been identified.

Layman's description

Infectious pancreatic necrosis (IPN) is the major endemic viral disease affecting the Atlantic salmon industry. In this project we demonstrated that there is considerable genetic variation in resistance (i.e. some families survive and others do not), we demonstrated that this variation is almost entirely to a single locus, and we identified genetic markers that are almost completely associated with this locus and hence can be used to breed fish for resistance. Further, we put considerable effort into identifying the genetic mechanisms of resistance, and we have a consistent gene expression signature which is indicative of infection in resistant vs. susceptible fish, and this has led to the identification of the most relevant pathways involved in IPN resistance. The genetic markers that we identified, using state-of-the-art techniques, are now being routinely used in salmon breeding programmes in Europe and South America, and the resulting fish are essentially resistant to this disease. This is best example of marker-assisted selection for disease resistance in any livestock species.

Key findings

This was a highly successful project: applying state-of-the-art genomic tools to a disease problem of major importance to the Atlantic Salmon industry (infectious pancreatic necrosis or IPN), obtaining results of fundamental scientific interest, obtaining tools that are directly usable by the industry, and guiding the use of the tools within the Atlantic salmon breeding industries of Europe and Chile (i.e. essentially worldwide). The key findings were:



1. IPN Resistance in salmon fry is controlled by a single locus.

Using large-scale challenge trials, we have demonstrated that a single major QTL accounts for nearly all the genetic variation in resistance in freshwater fry. The mode of action appears to be dose-dependent, being dominant at lower infection pressures or mortality rates, and additive at higher infection pressures. This result, consistent across age-classes, led to implementation of marker-assisted selection for IPN resistance.



2. Genetic differences in IPN resistance lead to a transcriptomic signature in infected fry

Transcriptomic comparisons of resistant and susceptible fry, pre- and post-infection, have identified a cascade of gene expression changes that determine consequences of differential resistance and the resultant IPN pathology.



3. Identification of SNPs associated with IPN resistance

Using novel state-of-the-art sequencing techniques (RAD sequencing) we identified SNPs in strong population-wide LD with the causal mutation – a valuable and directly exploitable result. The associations have been demonstrated to hold true in populations of >10,000 fish. These SNPs are now being used in breeding programmes in the salmon breeding industries of Europe and South America.
StatusFinished
Effective start/end date1/05/0831/10/10

Funding

  • BBSRC: £459,859.00

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