Help Me Genome, You’re My Only Hope: A Fishy Resistance Story

In a quiet fishing town along the coast of New Brunswick, a fish farmer discovers a salmon in one of his fish pens has bloodspots in its eyes and pale gills. Upon further investigation, he finds the fish has internal bleeding, an inflamed spleen and excess fluid in its swim bladder.

It is a sight no salmon producer wants to see. These are the tell-tale symptoms of infectious salmon anaemia (ISA), a viral disease that is harmless to humans but deadly to salmon.

"ISA is a terrible disease which nearly shut down Chile's salmon industry in 2007, and now the industry has salmon hatcheries that are under strict quarantine," says Prof. Elizabeth Boulding, Department of Integrative Biology. Boulding is a marine biologist with an interest in the evolution of genetic resistance to disease in salmon.

Closer to home, ISA outbreaks have also occurred in salmon farms in New Brunswick and other Maritime provinces. While vaccines and quarantine of breeding populations have ensured that these outbreaks were not as severe as Chile’s, the consequences of an infection remain dire. By law, a fish farmer must remove all of their stock if the virus is detected so that it does not spread to other regions.   

One strategy to help reduce the chance of ISA spread is to separate the saltwater broodstock from the freshwater nursery. This strategy has been adopted by Chilean salmon producers. Controlling the movement of fish offers some protection, but Boulding was interested in a different approach.  She wondered if a salmon’s own natural genetic resistance to ISA might be exploited to provide a better defense against the disease.  

Boulding and graduate student Forest Dussault analyzed survival data from two historical ISA “disease challenges” done at Saint Andrew’s Biological Station in New Brunswick.  The challenges were led by Professor Brian Glebe and Steven Leadbeater from the Department of Fisheries and Oceans, and by Professor Anthony Manning from the Research Productivity Council of New Brunswick. These challenges involved exposing young Atlantic salmon to a known concentrations of the ISA virus to see which fish survive.

Dussault and Boulding used a customized DNA test called a “SNP chip” to investigate genetic differences in 384 individual fish from families that had exhibited high variation in survival among siblings. The chip tested for 50,000 single nucleotide polymorphisms, also known as “SNPs”, which are small, single unit changes. The researchers then used classic quantitative trait locus (QTL) mapping within these families to compare the genome of both resistant and susceptible siblings.  QTL mapping shows which genetic differences between individuals are linked to a trait of interest (such as resistance to ISA).  

The results showed that there were DNA variations on multiple chromosomes that were related to ISA survival. One chromosome in particular, number 25, was “especially significant and accounted for 8.3% of the variance in survival,” says Boulding.  Other significant regions were found on Chromosomes 3 and 4.

These genetic variations are important because they can be used as DNA markers in breeding programs for more virus-resistant fish. 

According to Boulding, breeding for ISA resistance is preferable to genetic engineering.  While there’s no doubt that gene-editing tools like CRISPR-Cas9 and others can be useful, they only target a small portion of the genome, making it easy for the virus to evolve and overcome the fish’s resistance. In contrast, genomic selection targets an entire genome, which makes it harder for the ISA virus to evolve the ability to overcome the host’s genetic resistance.

Boulding cautions that selective breeding for a trait like ISA resistance still needs to keep other practical aspects of fish production in mind. 

“You need to weigh disease resistance against potential energy costs to the fish in other areas.  For example, you want to ensure that resistance to a particular disease does not substantially reduce growth rates.  This is important to keep production cost-efficient for the industry.”   

But for a destructive disease like ISA, Boulding’s findings offer new hope that the salmon genome could indeed hold the key to healthier fish, therefore ensuring that higher quality salmon ends up on the table of consumers.

Keng Ang, J.A.K. Elliott and Frank Powell from Cooke Aquaculture also contributed to the study.  This research was funded by Genome Canada.

Read the full study in the journal Aquaculture Research

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