Abstract
Natural antibodies (NAb) are antigen binding antibodies present in individuals without a previous exposure to this antigen. Keyhole limpet hemocyanin (KLH)-binding NAb levels were previously associated with survival in chickens. This suggests that selective breeding for KLH-binding NAb may increase survival by means of improved general disease resistance. Genome-wide association studies (GWAS) were performed to identify genes underlying genetic variation in NAb levels. The studied population consisted of 1,628 adolescent layer chickens with observations for titers of KLH-binding NAb of the isotypes IgM, IgA, IgG, the total KLH-binding (IgT) NAb titers, total antibody concentrations of the isotypes IgM, IgA, IgG, and the total antibodies concentration in plasma. GWAS were performed using 57,636 single-nucleotide polymorphisms (SNP). One chromosomal region on chromosome 4 was associated with KLH-binding IgT NAb, and total IgM concentration, and especially with KLH-binding IgM NAb. The region of interest was fine mapped by imputing the region of the study population to whole genome sequence, and subsequently performing an association study using the imputed sequence variants. 16 candidate genes were identified, of which FAM114A1, Toll-like receptor 1 family member B (TLR1B), TLR1A, Krüppel-like factor 3 (KLF3) showed the strongest associations. SNP located in coding regions of the candidate genes were checked for predicted changes in protein functioning. One SNP (at 69,965,939 base pairs) received the maximum impact score from two independent prediction tools, which makes this SNP the most likely causal variant. This SNP is located in TLR1A, which suggests a fundamental role of TLR1A on regulation of IgM levels (i.e., KLH-binding IgM NAb, and total IgM concentration), or B cells biology, or both. This study contributes to increased understanding of (genetic) regulation of KLH-binding NAb levels, and total antibody concentrations.
Highlights
Modern poultry production is facing high impact changes in production systems and management [1, 2]
Collection of samples and data was done according to Hendrix Genetics (HG) protocols, under the supervision of HG employees
Age was not significant for total IgA (tIgA), and total concentration (μg/ml) of antibodies (tIgT) but was kept in the model to be consistent with the other analyses
Summary
Modern poultry production is facing high impact changes in production systems and management [1, 2] These changes may enhance the risks of infectious disease, because of higher pathogenic pressure. Selective breeding for an improved immune system might be an important additional strategy to improve general disease resistance [3]. Selective breeding for an improved immune system requires a trait that is heritable, easy to measure, and preferentially related to general disease resistance [4]. High NAb titers (especially IgM) binding the overt antigen keyhole limpet hemocyanin (KLH) at adolescence, but not at later age, were related to lower mortality of commercial layer chickens [10,11,12]. To the best of our knowledge, no genome-wide association studies (GWAS) for NAb levels in chicken have been reported
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