Parkinson's Disease (PD) is a common neurodegenerative disorder in elderly humans. PD is characterized by neuronal loss in the substantia nigra and an aggregation of alpha-synuclein into Lewy bodies. The morbidity in humans is dependent on the genetic background, although the exact mechanisms of background effects of genetic variation are unknown. We turned to an alpha-synuclein aggregation model in the model nematode Caenorhabditis elegans to investigate the role of genetic variation on alpha-synuclein aggregation. We mapped regulators of gene expression (eQTL) in Recombinant Inbred Lines (RILs) constructed by crossing C. elegans strains NL5901 and SCH4856 which harbor the human alpha-synuclein. We found three regulatory hot-spots on Chromosome V. To pin-point the causal locus, three Introgression Lines (ILs) with wild type CB4856 introgressions in an N2 background on Chromosome V were crossed with NL5901. From each cross we obtained four genotypes: i) no alpha-synuclein and no introgression, ii) no alpha-synuclein but with introgression, iii) with alpha-synuclein but no introgression, iv) with alpha-synuclein and introgression. These verified the regulatory hotspot and through mining WormNet and CeNDR we found
hcp-1 as potential polymorphic modifier influencing human alpha-synuclein expression in C. elegans. We will follow up with updated RILs sequence and confirm the candidate modifier further with CRISPR/CAS-9 for gene function detection.