Research Article: Genome-Wide Scan and Test of Candidate Genes in the Snail Biomphalaria glabrata Reveal New Locus Influencing Resistance to Schistosoma mansoni

Date Published: September 15, 2015

Publisher: Public Library of Science

Author(s): Jacob A. Tennessen, Kaitlin M. Bonner, Stephanie R. Bollmann, Joel A. Johnstun, Jan-Ying Yeh, Melanie Marine, Hannah F. Tavalire, Christopher J. Bayne, Michael S. Blouin, David Blair.

Abstract: BackgroundNew strategies to combat the global scourge of schistosomiasis may be revealed by increased understanding of the mechanisms by which the obligate snail host can resist the schistosome parasite. However, few molecular markers linked to resistance have been identified and characterized in snails.Methodology/Principal FindingsHere we test six independent genetic loci for their influence on resistance to Schistosoma mansoni strain PR1 in the 13-16-R1 strain of the snail Biomphalaria glabrata. We first identify a genomic region, RADres, showing the highest differentiation between susceptible and resistant inbred lines among 1611 informative restriction-site associated DNA (RAD) markers, and show that it significantly influences resistance in an independent set of 439 outbred snails. The additive effect of each RADres resistance allele is 2-fold, similar to that of the previously identified resistance gene sod1. The data fit a model in which both loci contribute independently and additively to resistance, such that the odds of infection in homozygotes for the resistance alleles at both loci (13% infected) is 16-fold lower than the odds of infection in snails without any resistance alleles (70% infected). Genome-wide linkage disequilibrium is high, with both sod1 and RADres residing on haplotype blocks >2Mb, and with other markers in each block also showing significant effects on resistance; thus the causal genes within these blocks remain to be demonstrated. Other candidate loci had no effect on resistance, including the Guadeloupe Resistance Complex and three genes (aif, infPhox, and prx1) with immunological roles and expression patterns tied to resistance, which must therefore be trans-regulated.Conclusions/SignificanceThe loci RADres and sod1 both have strong effects on resistance to S. mansoni. Future approaches to control schistosomiasis may benefit from further efforts to characterize and harness this natural genetic variation.

Partial Text: Approximately one-sixth of the global burden of infectious disease in humans is due to parasites transmitted by invertebrate hosts [1]. A major avenue to combat these diseases lies in understanding the genetic and biochemical basis for natural variation in host resistance [2],[3]. The identification of resistance genes will facilitate genetic manipulation or marker-assisted selective breeding for resistance [4]. An understanding of host-parasite interactions may also suggest molecular therapeutic targets in the parasite. In addition, genes affecting host fitness and host-parasite co-evolution may serve as markers to predict and monitor host population responses to changes in parasite prevalence or virulence.

We have identified a genomic region in B. glabrata, RADres, at which each copy of a resistance allele cuts the odds of schistosome infection in half. The impact of this locus is of similar magnitude to the only other known resistance locus in the 13-16-R1 snail strain, sod1, which also conveys an approximately 2-fold effect with each copy of a resistance allele. Thus, combined homozygosity at both loci confers a 16-fold change in the odds of infection (from approximately 2:1 odds to approximately 1:8 odds). Other candidate genes show no association with resistance, including the GRC [3] and three loci with constitutive expression patterns correlated with resistance in this population [23].



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