Cloning, mapping and association studies of the ovine ABCG2 gene with facial eczema disease in sheep

Facial eczema (FE) is a hepatogenous mycotoxicosis in sheep caused by the fungal toxin sporidesmin. Resistance to FE is a multigenic trait. To identify QTL associated with this trait, a scan of ovine chromosomes was implemented. In addition, ABCG2 was investigated as a possible positional candidate gene because of its sequence homology to the yeast PDR5 protein and its functional role as a xenobiotic transporter. The sequence of ovine ABCG2 cDNA was obtained from liver mRNA by RT‐PCR and 5′ and 3′ RACE. The predicted protein sequence shares >80% identity with other mammalian ABCG2 proteins. SNPs were identified within exon 6, exon 9 and intron 4. The intron 4 SNP was used to map ABCG2 to ovine chromosome 6 (OAR6), about 2 cM distal to microsatellite marker OarAE101. Interestingly, this chromosomal region contains weak evidence for a FE QTL detected in a previous genome‐scan experiment. To further investigate the association of ABCG2 with FE, allele frequencies for the three SNPs plus three neighbouring microsatellite markers were tested for differences in sheep selected for and against FE. Significant differences were detected in the allele frequencies of the intronic SNP marker among the resistant, susceptible and control lines. No difference in the levels of ABCG2 expression between the resistant and susceptible animals was detected by Northern hybridisation of liver RNA samples. However, significantly higher expression was observed in sporidesmin‐dosed sheep compared with naïve animals. Our inference is that the ABCG2 gene may play a minor role in FE sensitivity in sheep, at least within these selection lines