GWAS analysis of QTL for enteric septicemia of catfish and their involved genes suggest evolutionary conservation of a molecular mechanism of disease resistance

Abstract

Disease problems cause major economic losses for the aquaculture industries. In catfish, enteric septicemia of catfish (ESC), caused by the bacterial pathogen Edwardsiella ictaluri, is the leading disease problem, causing tens of millions of dollars of annual economic losses. In this study, we conducted a genome-wide association study to determine quantitative trait loci (QTL) for resistance against ESC using an interspecific hybrid system. Five hundred fish were used in the analysis and 192 phenotypic extremes were used for genotyping with the catfish 250K SNP arrays. A genomic region on linkage group (LG) 1 was found significantly associated with ESC disease resistance. In addition, two suggestively associated QTL for ESC resistance were identified on LG 12 and LG 16. The nlrc3 duplicates were identified within all the three QTL, suggesting their importance in association with the QTL. Within the significant QTL on LG 1, 16 genes with known functions in immunity were identified. Of particular interest is the nck1 gene nearby the most significantly associated SNP. Nck1 was known to function as an adaptor to facilitating the pathogenesis of enteropathogenic Escherichia coli (EPEC) in humans. E. ictaluri and EPEC pathogens belong to the same bacterial family and share many common characteristics. The fact that nck1 is mapped in the QTL and that it was significantly upregulated in channel catfish intestine after ESC challenge suggested its candidacy of being involved in resistance/susceptibility of ESC.

A Review of Molecular Responses of Catfish to Bacterial Diseases and Abiotic Stresses

“…The oligo-polysaccharide (OP-S) subunits of the bacterium E. ictaluri play a major role during pathogenesis (Santander et al, 2014). Recently, it was reported that NCK1 may play a key role in the E. ictaluri pathogenesis by initiating actin pedestal formation, and linking the surface located ligand and host cell receptors (Zhou et al, 2017b). …”

“…Initially, a genome-wide association study (GWAS) was conducted with the fourth generation of backcross catfish progenies by using the 250K SNP array; a significant QTL on LG 1, and two suggestive QTL on LG 12 and 16 were identified to be associated with ESC disease resistance of catfish (Zhou et al, 2017b) ( Table 1 ). A set of 16 genes with immune related functions were identified within the significant QTL on LG 1.…”

“…A set of 16 genes with immune related functions were identified within the significant QTL on LG 1. Among them, the NCK1 gene was significantly upregulated in the intestine of channel catfish after E. ictaluri infection (Zhou et al, 2017a), and was considered as a possible candidate gene that confers ESC susceptibility, presumably by serving as an adaptor facilitating the pathogen entry into the host cells, similar to the situation of enteropathogenic Escherichia coli (EPEC) in humans (Zhou et al, 2017b). …”

“…With a well-assembled reference genome sequence, potential candidate genes within QTLs can be identified simultaneously, which is a useful way to understand the molecular mechanisms of a trait by identification of genes in proximity to QTL (Dikmen et al, 2013; Geng et al, 2015). As described above, GWAS was conducted to identify QTL associated with several important traits, including disease resistance for columnaris (Geng et al, 2015) and ESC (Zhou et al, 2017b; Shi et al, 2018; Tan et al, 2018), growth rate (Li et al, 2017), head size (Geng et al, 2016), body conformation (Geng et al, 2017), and low oxygen tolerance (Wang et al, 2017b; Zhong et al, 2017). As the global climate change worsens over time, it is important to develop heat-tolerant lines.…”

“…For the later, great genetic variations among catfish species and strains in response to diseases and stresses provide biological sources for the analysis of genetic and epigenetic regulation of disease resistance. After the publication of the channel catfish reference genome sequence (Liu et al, 2016), rapid progress has been made for the determination of QTL associated with disease resistance (Geng et al, 2015; Zhou et al, 2017b; Shi et al, 2018; Tan et al, 2018) and stress tolerance (Jin et al, 2017; Wang et al, 2017b; Zhong et al, 2017). …”