T cell transcription factor variants linked to Teladorsagia circumcincta resistance in sheep

Teladorsagia circumcincta is a common parasitic nematode of the sheep abomasum. Immunity is acquired through repeated exposure to the parasite. The immune response, pathology and clinical outcome vary greatly between animals. The aims of this project are: 1) understand how sheep respond to worm infection; 2) understand and identify genes associated with the response; 3) identify variation within those genes which may contribute to resistance. T helper cell (Th)1 and Th17 activation is associated with susceptibility (low antibody, high worm numbers) while a Th2 response is associated with resistance (high antibody levels and clearance of infection). The T helper cell transcription factors have been sequenced with splice variants and SNPs identified, which have the potential to cause effects to protein structure and function. RT-qPCR of 9 Resistant and 9 Susceptible lambs demonstrated that in the abomasal mucosa, there is a significant difference in expression of GATA3 (fold change [FC] 2.06, P-value < 0.001), RORC2 (FC -1.41, P-value 0.01) and RORC2v1 (FC -1.30, P-value 0.03). Absolute RT-qPCR analysis of GATA3 and RORC2v1 enabled calculation of copy numbers in 45 artificially infected lambs with statistical correlation of genotype with phenotype, identifying these genes as selection markers for future breeding programmes.