A major QTL for resistance against Salmonid Rickettsial Septicaemia in coho salmon (Oncorhynchus kisutch) maps to a narrow region on chromosome 21, implicating two candidate genes

The facultative intracellular bacterium Piscirickettsia salmonis causes Salmon Rickettsial Syndrome (SRS) in Coho salmon, Atlantic salmon, and other salmonids. SRS causes large mortalities in Chilean aquaculture and leads to heavy usage of antibiotics. In Atlantic salmon SRS resistance is a polygenic trait with moderate to large heritability. In coho salmon a large QTL for SRS-resistance was earlier found on chromosome 21. In the present study we have further characterized genetic resistance to SRS in coho salmon and searched for putative candidate genes underlying the QTL. The mean heritability of survival was 0.31 and 0.58 on the observed and liability scale, respectively. The QTL on chromosome 21 explained from 26% to 97% of genetic variation within 12 different datasets. Two SNPs were substantially more significant compared to other SNPs and in very strong linkage disequilibrium with each other. The resistance allele was found to be dominant over the susceptibility allele at these SNPs. One of the two SNPs was located within the first exon of two genes which are transcribed in opposite directions: a histidine triad nucleotide-binding protein 3 (hint3) gene and a gene (LOC109866666) encoding a long non-coding RNA (lncRNA). Genotypes at the SNP were correlated with expression levels at both hint3 and the lncRNA gene, and the differential expression was manifested in both SRS-challenged and non-challenged fish. The exonic SNP is located 3 base pairs upstream of the start codon of the hint3 gene, at a position which is crucial for effective translation according to the rules of Kozak. The resistance allele at the SNP correlates to increased expression levels and increased translation levels at hint3, although the latter remains to be experimentally proven. Thus, it seems plausible that the QTL is due to the action of the hint3 gene and/or the gene lncRNA gene encoded by LOC109866666. The hint3 gene on chromosome 21 is different from homologs in Atlantic salmon, and no Atlantic salmon homologs of LOC109866666 were found. Thus, it might be possible to increase SRS-resistance of Atlantic salmon by inserting the coho gene(s) through gene editing.