THE IPN-QTL STORY -

a game changer for IPN resistance and value to the

industry

Genetics is of huge importance to the effectiveness, sustainability and economy of food production

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Genetics is of huge importance to the effectiveness, sustainability and economy of food production

# eggs per hen per year

Genetics is of huge importance to the effectiveness, sustainability and economy of food production

Zuidhof et al. 2014.

Smolt

Production Year 1

Sea production

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Stripping Year 4

Eggs

3-4 year generation interval

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IPN QTL

S1 production Mid –Norway

12 2016

Salmon breeding 9

months to 4 kg

Genomic selection

sealice resistance

The IPN QTL story- from QTL to gene

Gene markers – «mapping» the genome

QTLs and gene markers

QTL = quantitative trait locus = an area of the genome associated with a specific trait

DNA = A, T, C and G

QTL-search

The hay stack is represented by the 3x109 billion basepairs

of the genome

With high density SNP chips we can genotype up to a million gene markers in individual fish

QTL-search

Testing the association between a trait and many gene markers along the genome

Several QTL’s are commonly found

Some have a stronger association to the trait

QTL-search: IPN resistance

First mapping: All linkage groups (chromosomes) 136 microsatellite markers

Second mapping: Chromosome 26 18 additional microsatellite markers

The effect of the IPN QTL in experimental challenge

Survival rates, in a challenge test for IPN resistance performed on Atlantic salmon fry, of offspring of parental pairs sharing 0, 1, 2, 3, or 4 copies of the highresistance allele (Q) of the QTL.

Published August 2009

Implementation of the IPN QTL in egg production 2009/2010

Norway: # IPN-outbreaks reduced by 90%

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IPN –vaccine IPN –QTL

Source: National Veterinary Institute / FHL

What is the mechanism behind IPN resistance? The search for the IPN resistance gene

Published June 2015

1st challenge: No genome sequence available

(of a very complex genome)

From: Lien et al., 2016: The Atlantic salmon genome provides insights into rediploidization

We had to construct a reference sequence of the IPN QTL region. Sequencing of BAC library from the region Co-challenge: Homologous region on chromosome 11 - had to be sequenced too Full genome sequencing of 45 QQ/qq animals. Map to reference sequence of the region, and look for sequence differences between QQ and qq animals

Significant SNPs positioned against genes

The three DNA polymorphisms most strongly associated with the QTL were located within a region harboring two epithelial cadherin genes (which we termed cdh1-1 and cdh1-2),

2nd challenge: What is the link between cadherin and IPN infection?

Cadherins are located in tight junctions between epithelial cells The role is to keep the cells attached to eachother

A fourth SNP was discovered inside the coding region of Cdh1-1

Source: Wikimedia commons

The IPN virus binds to Cdh1-1 Most likely the virus receptor

Direct protein interaction between IPNV and Cdh1-1 as verified by

coimmunoprecipitation (IP). IPNV infection of liver slices of qq and QQ fish

qq fish are infected by the virus,

and virus co-localizes with Cdh1-1

QQ fish are not infected – no signal

qq QQ

The IPN/cadherin interaction explains the suceptibility window of Atlantic salmon to IPN

First feeding fry and post-smolts are the most suceptible life stages Both are characterized of strong tissue growth and tissue remodelling, probably facilitating exposure of the receptor for the virus, enabling infection The IPN QTL stop infection by breaking the bond between the virus and the host cell

The IPN-QTL is included in all

AquaGen products