A genome-wide association study identifies two novel promising candidate genes affecting Escherichia coli F4ab/F4ac susceptibility in swine

Abstract

Enterotoxigenic Escherichia coli (ETEC) expressing F4 fimbria is the major pathogenic bacteria causing diarrhoea in neonatal and post-weaning piglets. Previous studies have revealed that the susceptibility to ETEC F4ab/F4ac is an autosomal Mendelian dominant trait and the loci controlling the F4ab/F4ac receptor are located on SSC13q41, between markers SW207 and S0283. To pinpoint these loci and further validate previous findings, we performed a genome-wide association study (GWAS) using a two generation family-based population, consisting of 301 piglets with phenotypes of susceptibility to ETEC F4ab/F4ac by the vitro adhesion test. The DNA of all piglets and their parents was genotyped using the Illumina PorcineSNP60 BeadChip, and 50,972 and 50,483 SNPs were available for F4ab and F4ac susceptibility, respectively, in the association analysis after quality control. In summary, 28 and 18 significant SNPs (p<0.05) were detected associated with F4ab and F4ac susceptibility respectively at genome-wide significance level. From these significant findings, two novel candidate genes, HEG1 and ITGB5, were firstly identified as the most promising genes underlying F4ab/F4ac susceptibility in swine according to their functions and positions. Our findings herein provide a novel evidence for unravelling genetic mechanism of diarrhoea risk in piglets.

Figure 1. Manhattan plots of genome-wide association for ETEC F4ab/F4ac susceptibility.

Negative log10-transformed p values of all tested SNPs for susceptibility to ETEC F4ab (Fig. 1A) and F4ac (Fig. 1B) are plotted against position on each of 19 chromosomes. Different chromosomes are represented by different colours. Chr. 19 stands for the X chromosome of swine.

Figure 2. Linkage disequilibrium (LD) pattern for common significant SNPs on SSC13.

LD blocks are marked with triangles. Values in boxes are LD (r²) between SNP pairs and the boxes are coloured according to the standard Haploview colour scheme: LOD>2 and D′ = 1, red; LOD>2 and D′<1, shades of pink/red; LOD<2 and D′ = 1, blue; LOD<2 and D′<1, white (LOD is the log of the likelihood odds ratio, a measure of confidence in the value of D′).