Epithelial Cadherin Determines Resistance to Infectious Pancreatic Necrosis Virus in Atlantic Salmon

Abstract

Infectious pancreatic necrosis virus (IPNV) is the cause of one of the most prevalent diseases in farmed Atlantic salmon (Salmo salar). A quantitative trait locus (QTL) has been found to be responsible for most of the genetic variation in resistance to the virus. Here we describe how a linkage disequilibrium-based test for deducing the QTL allele was developed, and how it was used to produce IPN-resistant salmon, leading to a 75% decrease in the number of IPN outbreaks in the salmon farming industry. Furthermore, we describe how whole-genome sequencing of individuals with deduced QTL genotypes was used to map the QTL down to a region containing an epithelial cadherin (cdh1) gene. In a coimmunoprecipitation assay, the Cdh1 protein was found to bind to IPNV virions, strongly indicating that the protein is part of the machinery used by the virus for internalization. Immunofluorescence revealed that the virus colocalizes with IPNV in the endosomes of homozygous susceptible individuals but not in the endosomes of homozygous resistant individuals. A putative causal single nucleotide polymorphism was found within the full-length cdh1 gene, in phase with the QTL in all observed haplotypes except one; the absence of a single, all-explaining DNA polymorphism indicates that an additional causative polymorphism may contribute to the observed QTL genotype patterns. Cdh1 has earlier been shown to be necessary for the internalization of certain bacteria and fungi, but this is the first time the protein is implicated in internalization of a virus.

Studying the Genetics of Resistance to CyHV-3 Disease Using Introgression from Feral to Cultured Common Carp Strains

“…Although it takes considerable efforts and longer time to develop, fish strains resistant to diseases are one desirable and sustainable solution to the problem (Ødegård et al, 2011; Gjedrem et al, 2012; Stear et al, 2012; Bishop and Woolliams, 2014). A prime example for one such successful development and the impact of this achievement on aquaculture comes from Atlantic salmon ( Salmo salar ), where strains with resistance to IPNV (infectious pancreatic necrosis virus) are now routinely used by significant sections of this industry (Houston et al, 2010; Yáñez et al, 2014; Moen et al, 2015). Finding that the trait variation contains a heritable genetic component is a prerequisite for breeding resistant fish strains.…”

QTL fine mapping and identification of candidate genes for growth-related traits in bighead carp ( Hypophthalmichehys nobilis )

“…QTL mapping has been proved to be an efficient approach to identify quantitative trait-associated markers or candidate genes, and has been successfully applied in some aquaculture species (Tong and Sun, 2015;Yue, 2014), such as Atlantic salmon (Baranski et al, 2010;Moen et al, 2015), rainbow trout (Reid et al, 2005) and tilapia (Cnaani et al, 2003), Arctic charr (Kuttner et al, 2011), Asian seabass (Wang et al, 2015b) and Japanese flounder (Song et al, 2012a). In this study, three significant and 8 suggestive QTL located at three QTL intervals with a PVE range of 18.6%-25.5%, indicating that some of these QTLs may have major effects and others may have minor effects on growth in bighead carp.…”

Association mapping reveals candidate loci for resistance and anaemic response to an emerging temperature‐driven parasitic disease in a wild salmonid fish

“…Thus, identification of several promising candidate genes for both parasite resistance and disease traits, such as the anaemic response, may accelerate the genetic improvement against PKD. For example, identified variants, which await validation in independent populations (see below), may be used for marker‐assisted selection to develop more resistant brown trout aquaculture strains (e.g., Moen et al., ). Similarly, the candidate SNPs and associated genes identified here may help to predict the response to future PKD outbreaks and benefit long‐term conservation management and hatchery programmes.…”