Somatic Mutations in Single Human Neurons from Patients with Congenital Neurodegenerative Diseases

Accumulating DNA lesions in neurons have been hypothesized to contribute to aging and neurodegeneration. Despite its pathophysiological importance, it has not been systematically examined reflecting ineffective methods. In this study, we developed a computational method for detecting genomic deletions in single-cell whole-genome sequencing data, and analyzed the whole genome of human single neurons. Single neurons were obtained from neurotypical individuals of various ages and from patients with three different congenital neurodegenerative diseases: Ataxia telangiectasia (AT), Cockayne syndrome (CS), and Xeroderma pigmentosum (XP). Single-neuron whole-genome sequencing data of AT brains are released here, and the data of other diseases are released in a separate dbGaP study (phs001485).