Intronic variance affect susceptibility to infection

First results of the NCN-founded project!

We genotyped a cytokine, lymphotoxin alpha (LTA), also known as tumor necrosis factor beta (TNF-β) and we identified several SNPs both in introns and exons within the gene.

The exonic polymorphism explained variation in susceptibility to infection with the nematode A. tetraptera, and intronic SNP variants explained a risk of infection with A. tetraptera, and blood parasites Bartonella sp. The exonic SNP significantly associated with a risk of infection was in strong linkage disequlibrium with two intronic SNPs. Moreover, SNPs affecting risk of infection with A. tetraptera and Bartonella sp were in strong LD with two MHC-DRB alleles, yet none of these MHC alleles was found to be associated with the risk of infection in a post-hoc analysis.

Our results reflects the complexity of associations between components of the immune system and confirms that a simplified, single-gene approach, does not provide a clear and comprehensive view upon its evolution. An importance of intronic variation suggest that we should broaden the scope of studies focused on host-parasite genetic interplay beyond commonly analysed coding parts of the genome, as not only exonic polymorphism is subject to parasite-driven selection.