Immunogenetic Basis of Chicken’s Heterophil/Lymphocyte Ratio Revealed by Genome-wide Indel Variants Analysis

Abstract

BackgroundEnhancing host immunity is an effective way to reduce morbidity in chickens. Heterophil/lymphocyte (H/L) ratio is associated with host disease resistance in birds. Chickens with different H/L ratio levels show different disease resistances, caused by a difference in the functional capacity of heterophils. In this study, an H/L directional breeding chicken line was constructed and a combined statistical analysis was used to explore the candidate genes and pathways related to H/L ratio based on whole-genome sequencing of 368 individuals, divided into a non-selection line (NS) and selection lines including G5, G9 and F2 of G9.ResultsHeterophils isolated from the H/L selection line had stronger phagocytosis and oxidative burst function than non-selection line. The 22.44 Mb genomic regions which annotated 300 protein-coding genes were selected in the genome of G9 compared to NS based on a genome-wide selective sweep. Several selective regions were identified containing genes like interferon induced with helicase C domain 1 (IFIH1) and moesin (MSN) associated with the intracellular receptor signaling pathway, C-C motif chemokine receptor 6(CCR6)、dipeptidyl peptidase 4(DPP4) and hemolytic complement (HC) associated with the negative regulation of leukocyte chemotaxis and tight junction protein 1(TJP1) associated with actin cytoskeleton organization. In addition, 45 genome-wide significant indels containing 29 protein-coding genes were also identified as associated with the H/L ratio based on genome-wide association study (GWAS). The expression of protein tyrosine phosphatase non-receptor type 5(PTPN5) and oxysterol binding protein like 5(OSBPL5) were positively correlated with H/L ratio and significantly different between the high and low H/L groups of the Beijing-You chicken. The A/A allelic frequency of indel 5_13108985 (P-value= 3.85E-06) within OSBPL5 gradually increased from the non-selection line to the G5 and G9 and the individuals with A/A exhibited lower H/L ratio. ConclusionsThe phagocytosis and oxidative burst functions were enhanced and 22.44 Mb genomic regions were selected with the directional selection of H/L ratio. PTPN5 and OSBPL5 genes were identified as candidate genes. These findings revealed the complex genetic mechanism of H/L ratio related to immunity and will allow selection for improving chicken immunity based on the H/L ratio.