Next generation sequencing approaches for novel gene discovery in South African Parkinson’s disease families

Christoffels, AlanPillay, Nikita Simone2023-05-222024-05-172023-05-222024-05-172022https://hdl.handle.net/10566/15292Philosophiae Doctor - PhDIn the last decade, next-generation sequencing (NGS) approaches have revolutionised the study of human genomics, particularly aiding the understanding of genetic diseases. Parkinson’s disease (PD) is a complex neurodegenerative disorder with a heterogenous genetic disposition. This disorder is clinically characterised by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Subsequently, this results in a severe decrease of available dopamine that manifests as a myriad of both motor and non-motor symptoms. Several genes, including α-synuclein (SNCA), parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2), PTEN induced putative kinase 1 (PINK1), and protein deglycase (DJ-1), are confirmed as disease-causing in autosomal recessive (AR), autosomal dominant (AD), early-onset (EO), and late-onset (LO) forms of the disorder.enAfrican AncestryBioinformaticsParkinson’s diseasePublic healthNeurodegenerative disorderNext generation sequencing approaches for novel gene discovery in South African Parkinson’s disease familiesUniversity of the Western Cape