GWAS reveals genomic associations with swine inflammation and necrosis syndrome

Abstract

The recently identified swine inflammation and necrosis syndrome (SINS) occurs in high prevalence from newborn piglets to fattening pigs and resembles an important concern for animal welfare. The primary endogenous syndrome affects the tail, ears, teats, coronary bands, claws and heels. The basis of clinical inflammation and necrosis has been substantiated by histopathology, metabolomic and liver transcriptomic. Considerable variation in SINS scores is evident in offspring of different boars under the same husbandry conditions. The high complexity of metabolic alterations and the influence of the boar led to the hypothesis of a polygenic architecture of SINS. This should be investigated by a genome-wide association study. For this purpose, 27 sows were simultaneously inseminated with mixed semen from two extreme boars. The mixed semen always contained ejaculate from a Pietrain boar classified as extremely SINS susceptible and additionally either the ejaculate from a Pietrain boar classified as SINS stable or from a Duroc boar classified as SINS stable. The 234 piglets were phenotyped on day 3 of life, sampled and genetically assigned to the respective boar. The piglets showed the expected genetic differentiation with respect to SINS susceptibility. The suspected genetic complexity was confirmed both in the number and genome-wide distribution of 221 significantly associated SNPs, and led to 49 candidate genes. As the SNPs were almost exclusively located in noncoding regions, functional nucleotides have not yet been identified. The results suggest that the susceptibility of piglets to SINS depends not only on environmental conditions but also on genomic variation.

Fig. 1

Principal Coordinates Analysis (PCA)-Plot based on the distance matrix as calculated with Tassel 5.0. Black = PI + offspring, red = PI− offspring, green = DU-offspring. Axis 1 and 2 represent the two main principal components creating genetic distances between offspring of the three boars

Fig. 2

Manhattan plot of GWAS with P-values for Z-transformed SINS scores. Negative decadic logarithm of the significance of SNPs in the genome-wide association study. The blue and red lines indicate chromosome-wide and genome-wide significance, respectively

Fig. 3

Q-Q plot of GWAS p-values Z-SINS (Z-transformed SINS scores)

Fig. 4

Distribution of significant SNPs with association to the different SINS genotypes across. The vertical lines characterise the extent of the 18 autosomes and the X chromosome in pigs (in Mbp). The pie charts on the lines correspond to the location of the SNPs with association to the SINS signs. The colours correspond to the indications in the legend. In the area of pie charts with several colours, there are associations with inflammation/necrosis in the area of several body parts. To the left of the vertical are the positional data in Mbp, to the right the numbers of the identified 71 chromosomal regions with significant associations in the GWAS

Fig. 5

Exemplary effects of selected SNPs on SINS phenotypes. The box-plots with whiskers represent the distribution of 90% of the piglets’ values. A SNP 9_90241577 (SSC_position); TT: n = 166; TG: n = 53; GG: n = 7. B SNP 12_44738423 (SSC_position); TT: n = 47; TC: n = 119; CC: n = 59. C SNP 15_76941405 (SSC_position); GG: n = 5; CG: n = 53; CC: n = 168

Fig. 6

Exemplary effects of SNP 12_44738423 on Z-transformed SINS scores by boar progeny. PI−: unfavourable Pietrain (n = 109); PI + : favourable Pietrain (n = 77); DU: Duroc (n = 48)