Rates and mechanisms of age-related somatic mutation in normal and Alzheimer brain

Characterizing the mechanisms of somatic mutations in the brain is important for understanding aging and disease, but little is known about the mutational patterns of different cell types. We performed whole-genome sequencing of 86 single oligodendrocytes, 20 mixed glia, and 56 single neurons from neurotypical individuals (0.4 to 104 years old) and compared the rates and signatures of somatic single nucleotide variants (sSNVs) and small insertions and deletions (indels) from each cell type. We further correlated this data with single-cell RNA (scRNA-seq) and chromatin accessibility (scATAC-seq) data generated from the same brains to compare the mutagenic processes in glia and neurons.