Harnessing the diversity of African genomes to drive novel disease gene and pathway discovery for Amyotrophic Lateral Sclerosis (ALS) Spectrum Disorders

Year of award: 2023


  • Dr Melissa Nel

    University of Cape Town

Project summary

Large-scale next-generation sequencing has rapidly advanced our understanding of the genetic architecture of Amyotrophic Lateral Sclerosis (ALS) spectrum disorders which is driving therapy development. Apart from our recent description of the first 100 cases, highly diverse and unique African genomes have not contributed to ALS gene discovery efforts. Critical insights into ALS biology remain to be gained from the application of long-read sequencing to study large structural variants and illuminate regions of the genome 'hidden' to short-read technology. This project proposes to include Africans in this next frontier of disease gene discovery by expanding the generation of whole genome sequencing data on African patients with ALS and related disorders (~600 over 6 years). The merits of this project lie not in sample numbers, but rather in the deep phenotyping and genomic characterization of unique ALS phenotypes in diverse population groups which have the potential to make novel discoveries with global impact. Africa remains decades behind the genomic revolution due to lack of sequencing infrastructure, bioinformatics expertise and African genomic reference data. This project will strengthen the Neurogenomics Research Programme at UCT's Neuroscience Institute, support African genomics capacity building and ultimately improve clinical care for ALS patients in Africa.