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

ABSTRACT

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.