Fine-resolution genetic mapping of advanced intercross lines of Biomphalaria glabrata

SUMMARY The control and treatment of schistosomiasis currently rely solely on praziquantel, a drug that has been in use for over 40 years. However, praziquantel is imperfect because it cannot kill juvenile schistosomes and does not prevent reinfection. Additionally, there is no effective vaccine against schistosome parasites. Therefore, alternative tools are urgently needed to fight schistosomiasis. One alternative strategy is the genetics-based biocontrol of snails by disrupting the intramolluscan life cycle of schistosomes before the release of cercariae (the infectious stage of schistosomes), thus preventing human infection. To support this strategy, we have developed advanced intercross lines of Biomphalaria glabrata, an important snail vector of the human blood fluke Schistosoma mansoni and a well-studied model for schistosomiasis research. These advanced intercross lines have been developed through our long-term efforts to develop genetic and genomic resources in B. glabrata aimed at understanding compatibility between snails and schistosomes. These AI snails possess four different resistance phenotypes: extreme susceptibility, moderate susceptibility, moderate resistance, and extreme resistance. These phenotypes enable us to explore the mechanisms that regulate the number of cercariae shed by individual snails, referred to as per capita cercarial production. Per capita cercarial production largely determines the total number of cercariae present in the water, thereby affecting schistosomiasis transmission in endemic areas. In this project, we propose to use double digest restriction-site associated DNA sequencing (ddRADseq) and pooled sample sequencing (Pool-seq) to genotype the AI snails. We will employ genome-wide association studies (GWAS) and quantitative trait loci (QTL) analyses to investigate the genomic regions and genes in those regions that control schistosome resistance, specifically per capita cercarial production. Completing this study will enhance our understanding of snail resistance to schistosomes, thus facilitating the development of innovative snail-targeted biocontrol programs for schistosomiasis, a parasitic disease that affects 251 million people worldwide.