Animal Breeding and Genomics Centre, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
Adaptation Physiology Group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
Genet Sel Evol. 2022 Mar 21;54(1):24. doi: 10.1186/s12711-022-00715-9.
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.
天然抗体(NAb)是存在于健康个体中的抗体,无需先前接触外源性抗原。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分歧选择实验分析 NAb 的遗传背景,特别是 TLR1A 基因的多态性的影响。
研究人群包括商业纯种种鸡白来航层线的基础种群和高、低选择线的 7 代鸟类。鸟类被选择用于总 KLH 结合 NAb 滴度(IgTotal)。通过酶联免疫吸附试验测定血液血浆中 NAb 滴度的 IgTotal 和抗体同种型 IgM 和 IgG。共有 10878 只鸡可获得 NAb 滴度。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)。母体环境效应解释了 NAb 表型变异的 2 到 3%。对 IgTotal 的选择导致第 7 代高、低线之间产生了 2.4 个滴度点(5.1 个遗传标准差)的遗传差异。对于 IgM,选择反应在低线比高线更高,呈不对称性。TLR1A C 等位基因在基础种群中的频率为 0.45,在第 7 代高、低线中分别为 0.66 和 0.04。TLR1A 多态性对 IgTotal 和 IgM 有较大且显著的影响。估计的基因型效应表明 TLR1A C 等位基因完全显性。检测到 IgM 和 IgTotal 的 TLR1A 多态性与世代的显著相互作用。
证实了 TLR1A 基因多态性对 IgTotal 和 IgM NAb 的影响。此外,我们提供了实验验证,即在一个受大量选择的数量性状上,具有显性基因作用的主要基因的等位基因频率发生变化。TLR1A 与世代的相互作用表明对环境因素敏感。