Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
University of Liège, Gembloux Agro-Bio Tech, Precision Livestock and Nutrition Unit, Passage des Déportés 2, 5030 Gembloux, Belgium.
Poult Sci. 2017 Jul 1;96(7):2040-2048. doi: 10.3382/ps/pex010.
Salmonella Enteritidis (SE) is a foodborne pathogen that negatively affects both animal and human health. Polymorphisms of the TLR4 gene may affect recognition by Toll-like receptor 4 (TLR4) of bacterial lipopolysaccharide (LPS), leading to differences in host resistance to pathogenic infections. The present study has investigated polymorphic loci of chicken TLR4 (ChTLR4) in ten chicken breeds, electrostatic potentials of mutant structures of TLR4, and a linkage analysis between allelic variation and survival ratio to infection with SE in specific-pathogen-free (SPF) White Leghorns. A total of 19 Single Nucleotide Polymorphisms (SNPs), of which 10 were novel, were found in chicken breeds. Seven newly identified amino acid variants (C68G, G674A, G782A, A896T, T959G, T986A, and A1104C) and previously reported important mutations (G247A, G1028A, C1147T, and A1832G) were demonstrated in the extracellular domain of the ChTLR4 gene. Significant changes in surface electrostatic potential of the ectodomain of TLR4, built by homology modeling, were observed at the Glu83Lys (G247A), Arg298Ser (A896T), Ser368Arg (A1104C), and Gln611Arg (A1832G) substitutions. Linkage analysis showed that one polymorphic locus G247A of TLR4 gene, common in all breeds examined, was significantly associated with increased resistance to SE in SPF White Leghorns chicks (log-rank P-value = 0.04). The genotypes from A1832G SNPs did not show statistically significant survival differences. This study has provided the first direct evidence that G247A substitution in ChTLR4 is associated with increased resistance to Salmonella Enteritidis.
肠炎沙门氏菌（SE）是一种食源性病原体，对动物和人类健康都有负面影响。TLR4 基因的多态性可能会影响 Toll 样受体 4（TLR4）对细菌脂多糖（LPS）的识别，从而导致宿主对致病感染的抵抗力存在差异。本研究调查了 10 个鸡品种中鸡 TLR4（ChTLR4）的多态性位点、TLR4 突变结构的静电势，以及特定病原体无感染（SPF）白来航鸡中 TLR4 等位基因变异与 SE 感染存活率之间的连锁分析。在鸡品种中发现了总共 19 个单核苷酸多态性（SNP），其中 10 个是新的。在 ChTLR4 基因的细胞外结构域中发现了 7 个新鉴定的氨基酸变体（C68G、G674A、G782A、A896T、T959G、T986A 和 A1104C）和以前报道的重要突变（G247A、G1028A、C1147T 和 A1832G）。通过同源建模构建的 TLR4 外显子表面静电势发生了显著变化，观察到 Glu83Lys（G247A）、Arg298Ser（A896T）、Ser368Arg（A1104C）和 Gln611Arg（A1832G）取代的变化。连锁分析表明，TLR4 基因的一个多态性位点 G247A 在所有研究的品种中都很常见，与 SPF 白来航鸡雏对 SE 的抵抗力增加显著相关（对数秩检验 P 值=0.04）。A1832G SNP 的基因型没有表现出统计学上的存活率差异。本研究首次直接证明了 ChTLR4 中的 G247A 取代与对肠炎沙门氏菌的抵抗力增加有关。
