Whole-genome sequencing identifies interferon induced protein IFI6 as a strong candidate gene for VNN resistance in European sea bass

Background Viral Nervous Necrosis (VNN) is major disease affecting of European sea bass. Understanding the biological mechanisms that underlie VNN resistance is thus important for the welfare of farmed fish and the sustainability of production systems. This study aimed at identifying key genomic regions and genes that determine VNN resistance in sea bass. Results We generated a dataset of around 900,000 single nucleotide polymorphisms (SNPs) identified from whole-genome sequencing (WGS) in the parental generation in two different commercial populations (pop A and pop B) comprising 2371 and 3428 European sea bass with phenotypic records for binary survival in a VNN challenge. In each commercial population, three cohorts were submitted to the redspotted grouper nervous necrosis virus (RGNNV) challenge by immersion and genotyped on a 57K SNP chip. After imputation of WGS SNPs from their parents, QTL mapping was performed using a Bayesian Sparse Linear Mixed Model (BSLMM). We found several QTL regions on different linkage groups (LG), most of which are specific to a single population, but a QTL region on LG12 was shared by both commercial populations. This QTL region is only 127 kB wide, and we identified IFI6, an interferon induced protein at only 1.9 kB of the most significant SNP. An unrelated validation population with 4 large families was used to validate the effect of the QTL, for which the survival of the susceptible genotype ranges from 39.8 to 45.4%, while that of the resistant genotype ranges from 63.8 to 70.8%. Conclusions We could precisely locate the genomic region implied in the main resistance QTL at less than 1.9 kb of the interferon alpha inducible protein 6 (IFI6), which has already been identified as a key player for other viral infections such as hepatitis B and C. This will lead to major improvements for sea bass breeding programs, allowing for greater genetic gain by using marker-assisted genomic selection to obtain more resistant fish. Further functional analyses are needed to evaluate the impact of the variant on the expression of this gene. ### Competing Interest Statement JB, ABa, BI, JSB are running the commercial breeding programs which provided fish for the present experiment. RM, ABe, MB and PH are advising them for the design and operation of these breeding programs. The other authors declare no conflict of interest.