A genome-wide association study explores the genetic determinism of host resistance to Salmonella pullorum infection in chickens

Abstract

Background Salmonella infection is a serious concern in poultry farming because of its impact on both economic loss and human health. Chicks aged 20 days or less are extremely vulnerable to Salmonella pullorum (SP), which causes high mortality. Furthermore, an outbreak of SP infection can result in a considerable number of carriers that become potential transmitters, thus, threatening fellow chickens and offspring. In this study, we conducted a genome-wide association study (GWAS) to detect potential genomic loci and candidate genes associated with two disease-related traits: death and carrier state. Methods In total, 818 birds were phenotyped for death and carrier state traits through a SP challenge experiment, and genotyped by using a 600 K high-density single nucleotide polymorphism (SNP) array. A GWAS using a single-marker linear mixed model was performed with the GEMMA software. RNA-sequencing on spleen samples was carried out for further identification of candidate genes. Results We detected a region that was located between 33.48 and 34.03 Mb on chicken chromosome 4 and was significantly associated with death, with the most significant SNP (rs314483802) accounting for 11.73% of the phenotypic variation. Two candidate genes, FBXW7 and LRBA, were identified as the most promising genes involved in resistance to SP. The expression levels of FBXW7 and LRBA were significantly downregulated after SP infection, which suggests that they may have a role in controlling SP infections. Two other significant loci and related genes (TRAF3 and gga-mir-489) were associated with carrier state, which indicates a different polygenic determinism compared with that of death. In addition, genomic inbreeding coefficients showed no correlation with resistance to SP within each breed in our study. Conclusions The results of this GWAS with a carefully organized Salmonella challenge experiment represent an important milestone in understanding the genetics of infectious disease resistance, offer a theoretical basis for breeding SP-resistant chicken lines using marker-assisted selection, and provide new information for salmonellosis research in humans and other animals.

Heritable Gut Microbiome Associated with Salmonella enterica Serovar Pullorum Infection in Chickens

“…The susceptibility or resistance to Salmonella is related to the host genetics ( 27 , 28 ). Several studies have discovered candidate genes associated with the death and carrier state of chickens after Salmonella infection ( 29 , 30 ). Our previous study revealed 43 host genetic markers associated with S .…”

E3 Ligase FBXW7 Facilitates Mycobacterium Immune Evasion by Modulating TNF-α Expression

“…Recently, FBXW7 has also been shown to have multiple functions in virus infection via interacting with diverse host molecules such as SHP2 ( Song et al., 2017 ), mTOR ( Xu et al., 2016 ), and NS5B ( Chen et al., 2016 ) in immune responses. Although a previous study reported that FBXW7 was downregulated after Salmonella infection ( Li et al., 2019 ), the function of FBXW7 in the immune responses during bacterial infection is still unknown.…”

“…Furthermore, recent research into the Ehrlichia chaffeensis TRP120 HECT E3 Ub ligase showed that it could target FBXW7 as a substrate to promote E. chaffeensis infection via maintaining the stability of Notch, c-Jun, and c -Myc and supporting cell survival ( Wang J. Y. et al., 2020 ). Recently, a genome-wide association study identified that FBXW7 was significantly downregulated in the chicken after infection with Salmonella pullorum , suggesting it may also play a role in controlling S. pullorum infection ( Li et al., 2019 ). Moreover, two studies of FBXW7’s function in macrophages suggested that FBXW7 played crucial roles in macrophage-pathogen interaction ( Song et al., 2017 ; Wang J. Y. et al., 2020 ).…”

Impaired Reproductive Function in Equines: From Genetics to Genomics

“…This gene has been associated with the dominant white coat color locus (W) which produces lethal disorders in the very early stages of gestation (W/W-genotype) [ 58 ], thus affecting fertility by indirect pathways. Similarly, recently, Velie, et al [ 78 ] identified a negative effect of inbreeding on ECA1 quantitative trait loci (QTL) in a large population of Norwegian-Swedish Coldblooded trotters. However, the same region was previously reported by Gottschalk et al [ 50 ] in association with the number of motile sperm, suggesting that the reduction in fertility from inbreeding could be partially mediated by a reduction in sperm quality ( Table 4 ).…”