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

African genomes—among the most genetically diverse on the planet—have been almost entirely excluded from the search for genes that cause motor neuron disease. The project will sequence the full genomes of roughly 600 African patients with amyotrophic lateral sclerosis (ALS) and related disorders, using long-read technology that can detect large structural variants hidden from standard short-read sequencing. This matters because nearly all ALS gene discovery has been done in people of European ancestry, leaving a vast reservoir of genetic variation untapped. African populations carry unique combinations of rare and common variants that could reveal entirely new disease pathways or protective factors. Without this data, the global understanding of ALS biology remains incomplete, and therapies developed from European genomes may not work equally well for African patients. If successful, the research could identify novel genes and mechanisms driving ALS, opening new targets for drug development. It will also build sequencing infrastructure, bioinformatics expertise, and reference genomic data for Africa—a region decades behind in the genomic revolution. In the longer term, this could improve diagnostic accuracy and clinical care for ALS patients across the continent. The project is primarily a fundamental science effort in disease gene discovery, but with clear downstream implications for equitable therapy development and African research capacity.