eQTL mapping in transgenic alpha-synuclein carrying Caenorhabditis elegans recombinant inbred line

Huang, Y.; Wang, Y. A.; van Sluijs, L.; Chen, Y.; Schoonerwoerd, S.; Tegelbeckers, V. I. P.; Vogels, D. H. J.; Riksen, J.; Kammenga, J. E.; Harvey, S. C.; Sterken, M. G.

doi:10.1101/2023.08.18.553811

bioRxiv · 10.1101/2023.08.18.553811

eQTL mapping in transgenic alpha-synuclein carrying Caenorhabditis elegans recombinant inbred line

Huang, Y.·Wang, Y. A.·van Sluijs, L.·Chen, Y.·Schoonerwoerd, S.·Tegelbeckers, V. I. P.·Vogels, D. H. J.·Riksen, J.·Kammenga, J. E.·Harvey, S. C.·Sterken, M. G.

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Abstract

Protein aggregation of -synuclein (S) is a genetic and neuropathological hallmark of Parkinsons disease (PD). Studies in the model nematode Caenorhabditis elegans suggested that variation of S aggregation depends on the genetic background. However, which genes and genetic modifiers underlie individual differences in S pathology remains unknown. To study the genotypic-phenotypic relationship of S aggregation, we constructed a Recombinant Inbred Line (RIL) panel derived from a cross between genetically divergent strains C. elegans NL5901 and SCH4856, both harboring the human S gene. As a first step to discover genetic modifiers 70 S-RILs were measured for whole-genome gene expression and expression quantitative locus analysis (eQTL) were mapped. We detected multiple eQTL hot-spots, many of which were located on Chromosome V. To confirm a causal locus, we developed Introgression Lines (ILs) that contain SCH4856 introgressions on Chromosome V in an NL5901 background. We detected 74 genes with an interactive effect between S and the genetic background, including the human p38 MAPK homologue pmk-1 that has previously been associated with PD. Together, we present a unique S-RIL panel for defining effects of natural genetic variation on S pathology, which contributes to finding genetic modifiers of PD.

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Huang, Y., Wang, Y. A., van Sluijs, L., Chen, Y., Schoonerwoerd, S., Tegelbeckers, V. I. P., Vogels, D. H. J., Riksen, J., Kammenga, J. E., Harvey, S. C., Sterken, M. G.. 2023-08-18. eQTL mapping in transgenic alpha-synuclein carrying Caenorhabditis elegans recombinant inbred line. https://doi.org/10.1101/2023.08.18.553811

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