Mixture of common and uncommon pathways and genes regulating primary and secondary immunoglobulin M responses in chickens

Immunoglobulin M (IgM) plays a crucial role in chicken immunity. IgM acts as the first line of defense against new and invading infections. The present study aims to identify possible pathways and genes affecting the IgM abundances in chicken blood plasma. A total of 312 F2 chickens resulted from the cross-breeding between fast and slow-growing chickens. By injecting Sheep Red Blood Cells (SRBC), IgM abundances were quantified at 56 and 63 days of age as primary (IgM1) and secondary (IgM2) immune responses, respectively. Candidate genes were identified using a genome-wide association study (GWAS), and functional annotation analysis, protein-protein interaction network (PPIN), and colocalization analysis of the identified candidate genes were performed. GWAS analysis for IgM1 and IgM2 traits led to the identification of 50 and 118 SNPs, respectively (FDR<0.05). The PPIN analysis identified 35 and 22 hub genes for IgM1 and IgM2 traits, respectively. In addition, one and three SNPs were found in the interferon-gamma and KLH regions, respectively, for IgM1. Likewise, 10 SNPs were identified in the LTA QTL (Quantitative trait locus) region for IgM2. Functional analysis showed that hub genes of RET, ANGPT1, ATP6V0B, LAMTOR2, and HSP90AA1 were significantly enriched in the pathways related to negative regulation of B-cell activation and proliferation, B-cell receptor signaling pathway, and negative regulation of T-helper 17 type immune response. Moreover, RNF220, ATP6V0B, KIF2C, and CDC20 genes were involved in most of the pathways related to both traits.