RCUK-CONICYT: Utilising functional genomic variation for improved disease resistance in Chilean salmon aquaculture

Lead Research Organisation: University of Edinburgh
Department Name: The Roslin Institute

Abstract

The economic burden of infectious disease hinders sustainable farmed Atlantic salmon production in Chile, and most aquaculture species worldwide. Targeting production of resistant stocks by selective breeding is a long term goal, and will contribute to disease control at a population level. Enabled by advanced genomics tools and technology, genetic improvement of disease resistance can be accelerated using genetic marker data to identify resistant parent fish in breeding programs. Further, the large families and the practical feasibility of large scale disease challenge experiments make salmon excellent models to discover genes and mutations underpinning host response to pathogens. Focusing on two of Chile's most problematic diseases (sea lice and Salmon Rickettsial Syndrome; SRS) in Atlantic salmon, this project will harness these genomic tools to (i) discover genes and functional variants affecting host response to infectious disease in farmed salmon and (ii) improve the use of genomic tools in breeding programs to increase population-level disease resistance via genomic prediction, and reduce the negative impact of outbreaks.

There is now a substantial genomic toolbox now available for Atlantic salmon (e.g. an advanced reference genome assembly and high density genetic marker arrays), this offers an unprecedented resource to locate specific genes and causative genomic variation underpinning host response to pathogens. In the proposed project, we will utilise data and samples previously collected from two large-scale disease challenge experiments (sea lice and SRS challenges. Genome-wide genetic marker data will be generated for all animals, and locating functional variants for resistance to each of the diseases will be achieved using the complementary approaches of (i) high power genome-wide association analysis; (ii) RNA-Seq (gene expression) comparison of the most resistant (R) and susceptible (S) individuals; (iii) Whole genome resequencing of pools of the R and pools of the S individuals combined with functional annotation. In addition to improving knowledge of the fundamental biology of host response to pathogens, these results have potential commercial relevance in at least two important fields. Firstly, the genes identified and their encoded proteins are potential drug or vaccination targets. Secondly, genomic regions and specific variants can be incorporated into selective breeding schemes, via improvement of the accuracy and cost-efficiency of genomic prediction of disease resistance. These results and techniques will lead to improved control of disease in Chilean aquaculture, and also provide a paradigm for tackling infectious disease problems via selective breeding in other farmed aquatic species worldwide.

Planned Impact

The primary goal of this project is to tackle infectious diseases impacting on Chilean salmon aquaculture via improvements in host genetic resistance. This will be achieved via a multi-faceted genomics approach based on data and samples collected from previous large scale disease challenge experiments in commercial Chilean salmon populations. Our direct links with the salmon breeding and production industries mean that the outcomes of this project are likely to be immediately and enthusiastically translated into practice for positive economic impact. There will also be downstream beneficial impact for the scientific community via the tools and knowledge developed within the project, particularly contributions to the fields of disease biology and selective breeding. Finally, the general public and policy makers will benefit from improved efficiency and sustainability of salmon production, and the project is likely to have wider ranging impacts on the production of other aquatic species worldwide.

Industry: The bacterial disease SRS and the ectoparasitic sea lice are the two largest disease threats to stable and sustainable Chilean salmon aquaculture. Sea lice present the biggest problem for salmon farming globally, causing issues relating to fish health and welfare and the environment, in addition to large negative financial impact. Therefore, routes to tackle lice and SRS are clear industry priorities. The outcomes of this project have both direct and long term potential for positive impact by reducing the number and severity of outbreaks of these diseases, in Chile but with potential for global application. This will be achieved firstly by the application of the cost-efficient genomic prediction for resistance in commercial salmon populations in Chile, via the link with AquaInnovo. The specific functional variants identified may have wider applications as molecular genetic tests for resistance that can be utilised by other breeders and producers. Further, the knowledge of the genes and mutations underpinning host resistance may guide vaccination and drug studies, or at least provide potential targets worthy of further research.

Scientific Community: The project outcomes will be of considerable interest and value for researchers in several related fields. The first and most obvious impact will be fundamental knowledge of the host response to SRS and sea lice in salmon. Since disease challenge experiments in aquaculture species tend to be undertaken on a scale that is not practical / possible in other species, the results may have significant value for improving understanding of host-pathogen interaction, and the causal factors underlying genetic variation in resistance. The incorporation of functional variation into genomic prediction models also presents an exciting avenue of research of potential interest to quantitative geneticists and animal breeders. Further, the project will provide substantial training for the PDRA as well as project management development opportunities for the team as a whole.

General Public and Policy Makers: The improvement of infectious disease control in aquaculture increases the stability and sustainability of a high quality protein product, potentially resulting in health benefits to society. In addition, the economic benefits to the industry will help support the tens of thousands of jobs that rely on aquaculture in Chile. The project also has potential to transform the control of infectious disease on a global aquaculture scale, through innovations in tools and techniques applied to selective breeding, including in developing countries. Government policy makers are likely to benefit from the research through its contribution to a sustainable aquaculture industry. The research will be communicated to the public via interaction with the media, presentations, publications, exhibitions and schools activities - supported by a policy of clear and open communication and public engagement.

Publications

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Houston R (2017) Future directions in breeding for disease resistance in aquaculture species in Revista Brasileira de Zootecnia

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Millacura F (2019) ParAlleL: A Novel Population-Based Approach to Biological Logic Gates in Frontiers in Bioengineering and Biotechnology

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Palaiokostas C (2017) Genome-wide approaches to understanding and improving complex traits in aquaculture species. in CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources

 
Description There have been extensive findings related to genetic and functional genomic basis of disease resistance in salmon. Gene expression profiling of healthy skin and infected skin from salmon infected with sea lice was performed. A number of enriched genes and pathways have been identified that may be key in the host response of salmon to lice, and these data will be overlayed with genome wide association mapping and whole genome sequencing comparison of resistant and susceptible individuals to learn more about the biology of host response to lice, and lead to potential solutions including improved selective breeding for resistance. In addition, the genetic basis of resistance to sea lice and salmon rickettsial syndrome has been investigated using genome-wide markers, detecting significant heritability for both diseases. Further, genome-wide significant QTL have been identified for host resistance to both diseases. Finally, the team have developed novel methods of improving cost-efficiency of genomic selection using reduced density marker panels.
Exploitation Route The collaborating breeding company (AquaInnovo) in Chile may use the results to improve their selective breeding for disease resistance.
Sectors Agriculture, Food and Drink

URL https://www.sciencedirect.com/science/article/pii/S0044848617304544
 
Description This project is a collaboration between ourselves, researchers in Chile and a multi-species aquaculture breeding and production company in Chile (AquaInnovo). The outputs from this project have included estimation of genetic parameters for resistance to sea lice and salmon rickettsial syndrome in AquaInnovo's breeding populations. These two diseases are currently the most problematic in Chile from an economic, environmental and animal welfare perspective. We have also located and characterized individual genes with functional association with resistance. Finally, we have tested new methods of genomic selection, including use of genotype imputation to reduce costs, and testing of new statistical models. These results are being applied within the breeding programmes of AquaInnovo, and will be disseminated for uptake by other aquaculture breeding companies. This will include extensive use of the techniques developed by breeding companies producing aquatic species farmed in DAC list countries, including tilapia and shrimp. The translation of selective breeding innovations from salmon to these less-developed sectors has historically happened quite quickly, and we expect this will be the case here. Improvement of disease resistance in aquaculture species will help develop aquaculture as an important source of high quality protein and energy for developing country populations. The outputs of this project were recognised by the shortlisting of the project for the prestigious Newton Prize, which seeks to highlight innovation and impact in Newton partner countries. https://www.benchmarkplc.com/news/sea-lice-and-srs-research-shortlisted-for-the-newton-prize/
First Year Of Impact 2016
Sector Agriculture, Food and Drink
Impact Types Cultural,Societal,Economic

 
Description Advisory to European Food Safety Authority
Geographic Reach Europe 
Policy Influence Type Participation in a advisory committee
Impact I was involved as an expert adviser to the European Food Safety Authority regarding the potential of a DNA based vaccine for Pancreas Disease in salmon to integrate into the genome of the salmon. The review outcome contributed to a decision that the first DNA vaccine was approved for use in salmon in Europe, with positive impact on disease control, environment, economy, and animal welfare.
URL https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2017.4689
 
Description Advancing European Aquaculture by Genome Functional Annotation
Amount € 6,000,000 (EUR)
Funding ID 817923 
Organisation European Union 
Sector Public
Country European Union (EU)
Start 05/2019 
End 04/2022
 
Description BBSRC Responsive Mode
Amount £900,000 (GBP)
Funding ID BB/R008612/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 03/2021
 
Description Genomic and nutritional innovations for genetically superior farmed fish to improve efficiency in European aquaculture
Amount € 6,149,963 (EUR)
Funding ID 818367 
Organisation European Union 
Sector Public
Country European Union (EU)
Start 01/2019 
End 12/2022
 
Description Horizon 2020 - Food security, sustainable agriculture and forestry, marine and maritime and inland water research - Ross Houston - Mediterranean Aquaculture Integrated Development
Amount £290,823 (GBP)
Funding ID 727315 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 05/2017 
End 04/2021
 
Description Horizon 2020 Call H2020-SFS-2016-2
Amount € 7,000,000 (EUR)
Funding ID 727315 
Organisation European Union 
Sector Public
Country European Union (EU)
Start 05/2017 
End 04/2021
 
Description Industry Partnership Award (TR) - Ross Houston - Improving resistance to infectious salmon anaemia using genome editing: Novel approaches to tackling viral disease in aquaculture
Amount £566,189 (GBP)
Funding ID BB/R008612/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 03/2021
 
Description Newton International Fellowship
Amount £96,501 (GBP)
Funding ID NF160037 
Organisation British Council 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2017 
End 02/2019
 
Description Research Grant - Ross Houston - Genomic selection to enhance tilapia breeding
Amount £449,897 (GBP)
Organisation Worldfish 
Sector Charity/Non Profit
Country Malaysia
Start 09/2018 
End 12/2022
 
Description Scottish Aquaculture Innovation Centre
Amount £1,000,000 (GBP)
Organisation Scottish Aquaculture Innovation Centre 
Sector Multiple
Country United Kingdom
Start 04/2018 
End 03/2020
 
Description Scottish Aquaculture Innovation Centre (SAIC) (TR) - Ross Houston - Genomic breeding for gill health and lice resistance in salmon: Towards a step improvement in accuracy and affordability
Amount £314,771 (GBP)
Funding ID 4640007 
Organisation Government of Scotland 
Department Scottish Funding Council
Sector Public
Country United Kingdom
Start 05/2018 
End 05/2020
 
Description Standard - Ross Houston - ROBUST-SMOLT Impact of early life history in freshwater Recirculation Aquaculture Systems on A. salmon robustness and susceptibility to disease at sea
Amount £202,913 (GBP)
Funding ID BB/S00436X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2019 
End 12/2021
 
Description Standard Grant - Ross Houston - AquaLeap: Innovation in Genetics and Breeding to Advance UK Aquaculture Production
Amount £403,285 (GBP)
Funding ID BB/S004343/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2019 
End 12/2021
 
Description Collaboration with Benchmark PLC in salmon gene editing 
Organisation Benchmark Holdings
PI Contribution This collaboration has been to develop a successful Industrial Partnership Award proposal for BBSRC into gene editing for disease resistance in salmon. Our team have developed gene editing facilities and capability in house for salmon (cell culture and embryos), and worked together with Benchmark to codevelop the project which begins on 1 April 2018. The reference code is BB/R008612/1.
Collaborator Contribution The partners are bringing substantial in kind contribution, cash contribution and expertise to the project. This includes access to samples and data from their salmon breeding programme in Norway, and access to year-round salmon gametes for gene editing experiments.
Impact Outputs include the successful award of project BB/R008612/1
Start Year 2017
 
Description Collaboration with University of Chile and AquaInnovo 
Organisation AquaChile
Country Chile 
Sector Private 
PI Contribution Chile is the second largest producer of Atlantic salmon in the world. This collaboration is based on research projects aimed at improving breeding for disease resistance in Chilean farmed salmon. The collaboration centres around a bilateral Newton project RCUK-CONICYT: Utilising functional genomic variation for improved disease resistance in Chilean salmon aquaculture. In this project, our team will run large-scale genomic analyses on disease challenged salmon samples, including from salmon challenged with sea lice and piscirickettsia salmonis - a major bacterial pathogen of salmon. This will include whole genome resequencing, analyses of differential gene expression profiles between resistant and susceptible fish, and genomic prediction analyses.
Collaborator Contribution The project partners (AquaChile and University of Chile) have provided access to over 5,000 samples from pedigreed Atlantic salmon stocks with associated data on sea lice and P. salmonis resistance. In addition, they provide significant practical and academic expertise to the collaboration.
Impact The outcomes of the collaboration to date have included training of postdoctoral researcher Diego Robledo in University of Chile in January 2017, and publications of peer-reviewed manuscripts: Genomics in aquaculture to better understand species biology and accelerate genetic progress. Jose M. Yáñez, Scott Newman, Ross D. Houston - 01 Apr 2015 - Frontiers in genetics Vol: 6. Genetics and genomics of disease resistance in salmonid species. José M Yáñez, Ross D Houston, Scott Newman - 2014 - Frontiers in genetics Vol: 5 Pages: 415 The future outcomes of the project will be improved methods of breeding for resistance to disease in Chilean salmon aquaculture. The collaboration includes quantitative genetics, disease biology, high throughput genomics / sequencing, and bioinformatics.
Start Year 2014
 
Description Collaboration with University of Chile and AquaInnovo 
Organisation University of Chile
Country Chile 
Sector Academic/University 
PI Contribution Chile is the second largest producer of Atlantic salmon in the world. This collaboration is based on research projects aimed at improving breeding for disease resistance in Chilean farmed salmon. The collaboration centres around a bilateral Newton project RCUK-CONICYT: Utilising functional genomic variation for improved disease resistance in Chilean salmon aquaculture. In this project, our team will run large-scale genomic analyses on disease challenged salmon samples, including from salmon challenged with sea lice and piscirickettsia salmonis - a major bacterial pathogen of salmon. This will include whole genome resequencing, analyses of differential gene expression profiles between resistant and susceptible fish, and genomic prediction analyses.
Collaborator Contribution The project partners (AquaChile and University of Chile) have provided access to over 5,000 samples from pedigreed Atlantic salmon stocks with associated data on sea lice and P. salmonis resistance. In addition, they provide significant practical and academic expertise to the collaboration.
Impact The outcomes of the collaboration to date have included training of postdoctoral researcher Diego Robledo in University of Chile in January 2017, and publications of peer-reviewed manuscripts: Genomics in aquaculture to better understand species biology and accelerate genetic progress. Jose M. Yáñez, Scott Newman, Ross D. Houston - 01 Apr 2015 - Frontiers in genetics Vol: 6. Genetics and genomics of disease resistance in salmonid species. José M Yáñez, Ross D Houston, Scott Newman - 2014 - Frontiers in genetics Vol: 5 Pages: 415 The future outcomes of the project will be improved methods of breeding for resistance to disease in Chilean salmon aquaculture. The collaboration includes quantitative genetics, disease biology, high throughput genomics / sequencing, and bioinformatics.
Start Year 2014
 
Description Strategic research partnership with WorldFish 
Organisation Worldfish
Country Malaysia 
Sector Charity/Non Profit 
PI Contribution A strategic research partnership has been established between Roslin and WorldFish. This partnership is initially focussed on use of advanced genetic and genomic technology to improve selective breeding of tilapia - one of the world's most important foodfish. Our contribution has included development of a research programme that builds on research performed in Atlantic salmon to inform strategies and techniques to implement genomic selection in WorldFish tilapia breeding programme.
Collaborator Contribution WorldFish run a family based selective breeding programme for tilapia and will provide data and samples from this programme to inform the research.
Impact This is a multidisciplinary partnership involving researchers involved in tilapia health, genetics, molecular biology and bioinformatics.
Start Year 2017
 
Description Organised a British Council Researcher Links conference in Mexico 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Co-organised a Researcher Links conference about Genomics in Aquaculture in Merida, Mexico in January 2017. This 5 day event featured around 40 scientists, with a mix of young researchers and mentors from both the UK and Mexico. This has already led to several collaborative links between UK and Mexico in this field.
Year(s) Of Engagement Activity 2017
URL https://sites.google.com/site/genomicsinaquaculturemxuk/home