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

Infectious pancreatic necrosis (IPN) is currently the most serious viral disease affecting the UK salmon farming industry. IPN is caused by infectious pancreatic necrosis virus (IPNV) which results in damage to the pancreas, intestine and liver of infected salmon. The annual economic loss to the UK aquaculture industry from IPN is estimated to be £5-10 million. Surviving salmon can become carriers of infection and then spread the disease to other susceptible fish, perpetuating IPN in both farmed and wild fish populations. Atlantic salmon vary in susceptibility to IPNV infection as they proceed through their life cycle. Newly-hatched salmon, i.e. fry, live in freshwater. They are particularly susceptible to IPN, and epidemics in hatcheries are typified by sudden large-scale mortalities. Subsequently, at the smolt life cycle stage, salmon alter their physiology in readiness for the move from freshwater to seawater. Salmon smolts (more specifically post-smolts) are susceptible to IPN during a period lasting from 2 - 10 weeks after seawater transfer. Certain families show genetic resistance to IPN, and we have previously shown that it is possible to identify resistant and susceptible salmon smolts using genetic markers. However, a number of questions relating to IPN resistance remain unanswered. In particular, whilst there is evidence that these genetic effects are consistent across different stages of the salmon life-cycle, i.e. consistent in smolts and fry, it is not conclusive. Furthermore, it is not known which specific genes and molecular pathways underlie genetic resistance to IPN. In an attempt to answer these questions we have three major objectives. First, we will confirm and describe genetic resistance to IPN in salmon fry and identify specific genomic regions affecting resistance. Second, we will determine which salmon genes work differently between genetically resistant and susceptible fish following infection. This will give insight into which biological mechanisms lead to genetic differences in resistance. Third, we will bring together all of the results to identify specific genes that may be responsible for the genetic resistance. The results of the study will strengthen salmon breeding programmes by providing genetic marker tests to identify IPN resistant fish early in the salmon life-cycle, thus reducing costs and reducing the number of diseased fish. The improved knowledge of the crucial genes defining IPN resistance may also contribute to the rational development of control measures against IPNV infections, including vaccination, and provide sensitive diagnostic tests. This project will be undertaken by researchers based at the Roslin Institute and the Institute of Aquaculture at Stirling University, and will also utilise the facilities and expertise of the Centre for Environment, Fisheries and Aquaculture Science, Weymouth. These UK researchers will collaborate with the Genomic Research on Atlantic Salmon Project (GRASP) in Canada, providing access to world-leading salmon genomics resources. The involvement of the innovative salmon breeding company Landcatch Natural Selection ensures that a clear route exists for the immediate commercial application of the results. This project is relevant to research supported by the BBSRC aimed at the analysis of the mechanisms of immune function and disease, and fits the priority relating to the control of infectious diseases, including the genetics of host resistance to infection.

Infectious pancreatic necrosis (IPN) is the most serious viral disease affecting the UK salmon farming industry and is responsible for annual losses of £5-10 million. IPN affects two distinct life cycle stages of Atlantic salmon / fry and smolts. We have previously defined strong genetic variation in IPN resistance and mapped resistance QTL within salmon smolts but, beyond clear indications that it exists, little is known about resistance in fry. Detailed knowledge of genetic resistance in salmon fry would be particularly valuable and the comparison with resistance in smolts would be of obvious scientific interest. Therefore we propose to work with Atlantic salmon fry to i.) quantify genetic variation in IPN resistance and resolve it to specific QTL regions, ii.) determine genes and pathways underlying differences in resistance, and iii.) synthesize structural and functional genomics outputs to identify candidate quantitative trait genes. Using established experimental IPN virus challenge models, observed patterns of mortality of fry will allow i.) genetic variation to be quantified and related to resistance in smolts and ii.) QTL to be mapped using a genome scan and related to those in smolts. The differential transcription patterns of i.) fry from susceptible and resistant families, and ii.) full siblings carrying alternative QTL alleles will be determined by profiling infected fish using the TRAITS Atlantic salmon cDNA microarray and qRT-PCR. This will help to establish the molecular mechanisms that underlie genetic differences in resistance and will lead to candidate genes that will be integrated with a fine-mapping and structural genomics approach to bring us closer to the QTG. Information on the genes and pathways underlying genetic resistance to IPN will lead to more robust and effective selection for resistance, facilitate the design of vaccines and immunostimulants and improve our understanding of the basic biology of an unusual viral infection.