A Quarter Century of advances in human PD genetics, C. elegans technologies and functional modelling of Mendelian PD in C. elegans
Timeline of advancements in our understanding of PD genetics, from the identification of the first mendelian PD gene encoding for α-synuclein in 1997, to the novel and expanding insights recently gleaned through GWAS. Human PD genes are indicated above the timeline and have individual colours assigned to them, with the milestones in C. elegans research of this gene or orthologues beneath the timeline indicated with the same colour. Concurrent with the growth of human genetic data in PD, there has been much advancement in C. elegans technologies relevant to PD research, illustrated with grey boxes. As a model, C. elegans has been pivotal in the development of RNAi technology, whole organism genome sequencing and recently, CRISPR/Cas9 genome editing, enabling the dissection of the effect of point mutations in orthologues. Many of the Mendelian PD genes presented have been studied in C. elegans functional models, with promising conservation demonstrated. Some of these are discussed in depth, throughout this review.