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.

中文翻译：

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全基因组关联研究探索了宿主对鸡白痢沙门氏菌感染的抗性的遗传决定论。

背景技术沙门氏菌感染是家禽养殖中的一个严重问题，因为它对经济损失和人类健康都有影响。年龄在20天或以下的雏鸡极易感染白痢沙门氏菌（SP），从而导致很高的死亡率。此外，SP感染的爆发可能导致大量携带者成为潜在的传播者，从而威胁到同伴的鸡和后代。在这项研究中，我们进行了全基因组关联研究（GWAS），以检测潜在的基因组位点和与两种疾病相关特征相关的候选基因：死亡和携带者状态。方法通过SP攻击实验对818只禽的死亡和携带者状态特征进行表型分析，并使用600 K高密度单核苷酸多态性（SNP）阵列进行基因分型。使用单标记线性混合模型的GWAS是通过GEMMA软件执行的。对脾脏样品进行RNA测序以进一步鉴定候选基因。结果我们检测到一个位于鸡第4号染色体上33.48和34.03 Mb之间的区域，该区域与死亡显着相关，其中最显着的SNP（rs314483802）占表型变异的11.73％。鉴定了两个候选基因FBXW7和LRBA是与SP抗性相关的最有前途的基因。SP感染后FBXW7和LRBA的表达水平显着下调，这表明它们可能在控制SP感染中起作用。另外两个重要的基因座和相关基因（TRAF3和gga-mir-489）与携带者状态相关，这表明与死亡相比，不同的多基因决定论。此外，在我们的研究中，基因组近交系数与每个品种对SP的抗性均不相关。结论GWAS的结果经过精心组织的沙门氏菌挑战实验，是理解传染病抗性遗传学的重要里程碑，为使用标记辅助选择育种抗SP的鸡系提供了理论基础，并为沙门氏菌病研究提供了新的信息。在人类和其他动物中。