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Background 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. Methods 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. Results 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. Conclusions 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.

Divergent selection for natural antibodies in poultry in the presence of a major gene