A heterophil/lymphocyte-selected population reveals the phosphatase PTPRJ is associated with immune defense in chickens

Quantification of leukocyte profiles is among the simplest measures of animal immune function. However, the relationship between H/L ratio and innate immunity and the measure’s utility as an index for heterophil function remains to be analyzed. Variants associated with H/L ratio were fine-mapped based on the resequencing of 249 chickens of different generations and an F2 segregating population generated by crossing selection and control lines. H/L ratio in the selection line was associated with a selective sweep of mutations in protein tyrosine phosphatase, receptor type J (PTPRJ), which affects proliferation and differentiation of heterophils through its downstream regulatory genes. The SNP downstream of PTPRJ (rs736799474) have a universal effect on H/L, with CC homozygotes exhibiting improved heterophil function because of downregulated PTPRJ expression. In short, we systematically elucidated the genetic basis of the change in heterophil function resulting from H/L selection by identifying the regulatory gene (PTPRJ) and causative SNP.