Natural antibodies (NAb) are antibodies that are present in a healthy individual without requiring previous exposure to an exogenous antigen. Selection for high NAb levels might contribute to improved general disease resistance. Our aim was to analyse the genetic background of NAb based on a divergent selection experiment in poultry, and in particular the effect of a polymorphism in the TLR1A gene. The study population consisted of a base population from a commercial pure-bred elite white leghorn layer line and seven generations of birds from a High and Low selection line. Birds were selected for total KLH-binding NAb titer (IgTotal). An enzyme-linked immunosorbent assay was performed to determine NAb titers in blood plasma for IgTotal and the antibody isotypes IgM and IgG. NAb titers were available for 10,878 birds. Genotypes for a polymorphism in TLR1A were determined for chickens in generations 5, 6 and 7. The data were analysed using mixed linear animal models. The heritability estimate for IgM was 0.30 and higher than that for IgG and IgTotal (0.12). Maternal environmental effects explained 2 to 3% of the phenotypic variation in NAb. Selection for IgTotal resulted in a genetic difference between the High and Low line of 2.4 titer points (5.1 genetic standard deviation) in generation 7. For IgM, the selection response was asymmetrical and higher in the Low than the High line. The frequency of the TLR1A C allele was 0.45 in the base population and 0.66 and 0.04 in generation 7 of the High and Low line, respectively. The TLR1A polymorphism had large and significant effects on IgTotal and IgM. Estimated genotypic effects suggest full dominance of the TLR1A C allele. Significant TLR1A by generation interactions were detected for IgM and IgTotal. The effect of a polymorphism in the TLR1A gene on IgTotal and IgM NAb was confirmed. Furthermore, we provide experimental verification of changes in allele frequencies at a major gene with dominant gene action on a quantitative trait that is subjected to mass selection. TLR1A by generation interactions indicate sensitivity to environmental factors.

中文翻译：

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存在主要基因的家禽中天然抗体的发散选择

天然抗体 (NAb) 是存在于健康个体中的抗体，无需事先暴露于外源性抗原。选择高 NAb 水平可能有助于提高一般疾病抵抗力。我们的目的是基于家禽的不同选择实验分析NAb的遗传背景，特别是TLR1A基因多态性的影响。研究群体包括来自商业纯种精英白来亨蛋鸡系的基础群体和来自高和低选择系的七代鸟类。选择鸟类的总 KLH 结合 NAb 滴度 (IgTotal)。进行酶联免疫吸附测定以确定血浆中 IgTotal 和抗体同种型 IgM 和 IgG 的 NAb 滴度。NAb 滴度可用于 10,878 只鸡。在第 5、6 和 7 代鸡中确定 TLR1A 多态性的基因型。使用混合线性动物模型分析数据。IgM 的遗传力估计值为 0.30，高于 IgG 和 IgTotal (0.12)。母体环境影响解释了 2% 到 3% 的 NAb 表型变异。IgTotal 的选择导致第 7 代高线和低线之间的遗传差异为 2.4 个滴度点（5.1 遗传标准偏差）。对于 IgM，选择反应是不对称的，并且在低线中高于高线。TLR1A C 等位基因在基础人群中的频率为 0.45，在高线和低线的第 7 代中分别为 0.66 和 0.04。TLR1A 多态性对 IgTotal 和 IgM 有很大的影响。估计的基因型效应表明 TLR1A C 等位基因完全占主导地位。在 IgM 和 IgTotal 中检测到显着的 TLR1A 世代相互作用。证实了 TLR1A 基因多态性对 IgTotal 和 IgM NAb 的影响。此外，我们提供了对主要基因的等位基因频率变化的实验验证，该主要基因对受大量选择的数量性状具有显性基因作用。TLR1A 通过世代相互作用表明对环境因素的敏感性。我们提供了对主要基因的等位基因频率变化的实验验证，该主要基因具有显性基因作用于受质量选择的数量性状。TLR1A 通过世代相互作用表明对环境因素的敏感性。我们提供了对主要基因的等位基因频率变化的实验验证，该主要基因具有显性基因作用于受质量选择的数量性状。TLR1A 通过世代相互作用表明对环境因素的敏感性。