Identifying chicken alloantigens to understand their influence on disease and production traits

Self-recognition system components including red blood cell antigens and the major histocompatibility complex (MHC) are alloantigens found on multiple cell types. Specific polyclonal antisera reactivity identified fourteen chicken erythrocyte alloantigens (A, B, C, D, E, H, I, J, K, L, M, N, P, R). Multiple associations between alloantigen variation and disease or production traits have been reported. Blood group B, the MHC, was the first system whose genes and function were classified. Recent investigations sought to identify genes and chromosomal locations for other alloantigen systems. Phenotype-pooled DNA from pedigree and non-pedigree chickens having known alloantigen types underwent genome-wide association (GWAS) analyses using data from either 600K or 54K SNP panels. DNA from independent samples was used to confirm candidate gene associations. Genome sequences from elite production and experimental lines with identified alloantigen alleles were examined. Candidate genes within strong GWAS peaks were bioinformatically screened for cell surface expression and co-segregation of non-synonymous SNP with serologically defined haplotypes. Specific genes have now been identified for four alloantigen systems. Linked genes found on chromosome 26 are A = complement component 4 binding protein, membrane (C4BPM) and E = Fc fragment of IgA and IgM receptor (FCAMR). The D system gene (CD99) is on chromosome 1. Alloantigen I, equivalent to the human Rh blood group locus (RHCE), lies on chromosome 23 including deletions covering > 6,000 bp predicted to affect the last seven RHCE gene exons. Candidate regions were found for alloantigens L, H, and M on chromosomes 4, 24, and 26, respectively. Small sample size hindered definitive gene identification. In summary, four alloantigen genes with allele associated variants have been identified. Genes C4BPM, CD99, FCAMR, and RHCE play roles in processes such as complement regulation and immune cell migration. Chromosomal locations have been defined for three other alloantigen systems. Identification of specific genes responsible for the blood system alleles provides tools to study these chicken alloantigens for relationships with disease and production traits.