T helper cell transcription factor polymorphisms in nematode-infected 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 RORA variant 5 is significantly differentially expressed (P-value = 0.014). Absolute RT-qPCR analysis of the RORA variants (TV2 and 5) calculated the copy number of all 45 artificially infected lambs enabling statistical correlation of genotype with phenotype: TV2 correlates significantly with IgA levels (ρ= -0.30, P= 0.04); TV5 correlates significantly with adult worm burden (ρ= -0.53, P= 0.0002) and faecal egg count (ρ= -0.55, P= <0.0001).