
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.30.610565
preprint
1
Article
Immune targets for schistosomiasis control identified by a genome-wide association study of East African snail vectors
Pennance Tom http://orcid.org/0000-0003-4898-462X

Tennessen Jacob A http://orcid.org/0000-0002-5015-4740

Spaan Johannie M http://orcid.org/0000-0002-2528-3583

McQuistan Tammie
Ogara George
Rawago Fredrick
Andiego Kennedy
Mulonga Boaz
Odhiambo Meredith
Mutuku Martin W
Mkoji Gerald M http://orcid.org/0000-0003-3417-1644

Loker Eric S http://orcid.org/0000-0002-2916-9868

Odiere Maurice R http://orcid.org/0000-0001-7561-4873

Steinauer Michelle L http://orcid.org/0000-0002-3745-2401

02 9 2024
2024.08.30.610565https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.30.610565
nihpp-2024.08.30.610565.pdf
Schistosomiasis, afflicting >260 million people worldwide, could be controlled by preventing infection of freshwater snail vectors. Intestinal schistosomiasis, caused by Schistosoma mansoni, occurs predominantly in Sub-Saharan Africa and is vectored by Biomphalaria sudanica and related Biomphalaria species. Despite their importance in transmission, very little genomic work has been initiated in African snails, thus hindering development of novel control strategies. To identify genetic factors influencing snail resistance to schistosomes, we performed a pooled genome-wide association study (pooled-GWAS) on the offspring of B. sudanica collected from a persistent hotspot of schistosomiasis in Lake Victoria, Kenya, and exposed to sympatric S. mansoni. Results of the pooled-GWAS were used to develop an amplicon panel to validate candidate loci by genotyping individual snails. This validation revealed two previously uncharacterized, evolutionarily dynamic regions, SudRes1 and SudRes2, that were significantly associated with resistance. SudRes1 includes receptor-like protein tyrosine phosphatases and SudRes2 includes a class of leucine-rich repeat-containing G-protein coupled receptors, both comprising diverse extracellular binding domains, suggesting roles in pathogen recognition. No loci previously tied to schistosome resistance in other snail species showed any association with compatibility suggesting that loci involved in the resistance of African vectors differ from those of neotropical vectors. Beyond these two loci, snail ancestry was strongly correlated with schistosome compatibility, indicating the importance of population structure on transmission dynamics and infection risk. These results provide the first detail of the innate immune system of the major schistosome vector, B. sudanica, informing future studies aimed at predicting and manipulating vector competence.
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