Abstract
BackgroundMore than 2 billion individuals worldwide suffer from helminth infections. The highest parasite burdens occur in children and helminth infection during pregnancy is a risk factor for preterm delivery and reduced birth weight. Therefore, helminth infections can be regarded as a strong selective pressure.ResultsHere we propose that candidate susceptibility genes for parasitic worm infections can be identified by searching for SNPs that display a strong correlation with the diversity of helminth species/genera transmitted in different geographic areas. By a genome-wide search we identified 3478 variants that correlate with helminth diversity. These SNPs map to 810 distinct human genes including loci involved in regulatory T cell function and in macrophage activation, as well as leukocyte integrins and co-inhibitory molecules. Analysis of functional relationships among these genes identified complex interaction networks centred around Th2 cytokines. Finally, several genes carrying candidate targets for helminth-driven selective pressure also harbour susceptibility alleles for asthma/allergy or are involved in airway hyper-responsiveness, therefore expanding the known parallelism between these conditions and parasitic infections.ConclusionsOur data provide a landscape of human genes that modulate susceptibility to helminths and indicate parasitic worms as one of the major selective forces in humans.
Highlights
More than 2 billion individuals worldwide suffer from helminth infections
We have previously addressed the role of helminths as selective agents in human evolution analyzing a large set of human genes encoding interleukins and their receptors; we demonstrated that the pressure imposed by parasitic worms on these genes has been stronger than the one due to viral and microbial agents [4]
Here we propose that candidate susceptibility genes for parasitic worm infections can be identified by searching for single nucleotide polymorphism (SNP) that display a strong correlation with the diversity of helminth species/genera transmitted in different geographic areas
Summary
More than 2 billion individuals worldwide suffer from helminth infections. The highest parasite burdens occur in children and helminth infection during pregnancy is a risk factor for preterm delivery and reduced birth weight. We have previously addressed the role of helminths as selective agents in human evolution analyzing a large set of human genes encoding interleukins and their receptors; we demonstrated that the pressure imposed by parasitic worms on these genes has been stronger than the one due to viral and microbial agents [4]. The reasons for this observation likely lie in the long-term relationship between humans and helminths, in the relatively slow evolutionary rates of these parasites and in their geographic distribution being considerably stable. We aimed at exploiting the selection signatures left by these pathogens on human genes to identify, at the genomewide level, candidate genes and variants that may have been subjected to helminth-driven selective pressure
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