Browsing by Author "Pillay, Nikita Simone"

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    Current Status of Next-Generation Sequencing Approaches for Candidate Gene Discovery in Familial Parkinson´s Disease
    (Frontiers in Genetics, 2022) Pillay, Nikita Simone
    Parkinson’s disease is a neurodegenerative disorder with a heterogeneous genetic etiology. The advent of next-generation sequencing (NGS) technologies has aided novel gene discovery in several complex diseases, including PD. This Perspective article aimed to explore the use of NGS approaches to identify novel loci in familial PD, and to consider their current relevance. A total of 17 studies, spanning various populations (including Asian, Middle Eastern and European ancestry), were identified. All the studies used whole-exome sequencing (WES), with only one study incorporating both WES and whole-genome sequencing. It is worth noting how additional genetic analyses (including linkage analysis, haplotyping and homozygosity mapping) were incorporated to enhance the efficacy of some studies. Also, the use of consanguineous families and the specific search for de novo mutations appeared to facilitate the finding of causal mutations. Across the studies, similarities and differences in downstream analysis methods and the types of bioinformatic tools used, were observed. Although these studies serve as a practical guide for novel gene discovery in familial PD, these approaches have not significantly resolved the “missing heritability” of PD.We speculate that what is needed is the use of third-generation sequencing technologies to identify complex genomic rearrangements and new sequence variation, missed with existing methods. Additionally, the study of ancestrally diverse populations (in particular those of Black African ancestry), with the concomitant optimization and tailoring of sequencing and analytic workflows to these populations, are critical. Only then, will this pave the way for exciting new discoveries in the field.
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    The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data
    (Nature Research, 2023) Hampton, Leonard L; Ruqaya, Murtadha; Martinez-Carrasco, Alejandro; Pillay, Nikita Simone
    Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD
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    Next generation sequencing approaches for novel gene discovery in South African Parkinson’s disease families
    (University of the Western Cape, 2022) Pillay, Nikita Simone; Christoffels, Alan
    In 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.