Expression profiling of the GBP1 gene as a candidate gene for porcine reproductive and respiratory syndrome resistance.

A genomic region in pig chromosome 4 has been previously associated with higher viraemia levels and lower weight gain following porcine reproduction and respiratory syndrome virus (PRRSV) infection. The region includes the marker WUR1000125, a G>A polymorphism next to a putative polyadenylation site in the 3'-untranslated region (3'-UTR) of the guanylate-binding protein 1, interferon-induced (GBP1) gene. The protein encoded by GBP1 is a negative regulator of T-cell responses. We show here that GBP1 expression is lower in liver and tonsils of pigs carrying the WUR1000125-G allele due to differential allele expression (allele A expression is 1.9-fold higher than for allele G). We also show that the GBP1 gene has two active polyadenylation signals 421 bp apart and that polyadenylation usage is dependent on the WUR1000125 genotype. The distal site is the most prevalently used in all samples, but the presence of the A allele favours the generation of shorter transcripts from the proximal site. This is confirmed by a differential allele expression study in AG genotype liver and tonsil samples. The interaction between WUR1000125 and other mutations identified in the 5'- and 3'-UTR regions of this gene needs to be studied. In conclusion, our study indicates that the WUR1000125 mutation is associated with changes in the expression of the negative T-cell regulator GBP1 gene. However, the chromosome 4 locus for PRRSV viraemia levels and weight gain contains a cluster of four other GBP genes that remain to be studied as candidate genes for this QTL.

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