Brain somatic CNVs initially were identified by comparing the sequences of bulk DNA derived from multicellular samples of different brain regions to the sequences of DNA derived from somatic tissues (96, 97). The first single-cell study of neuronal CNVs analyzed 110 human frontal cortex neurons and found that 13 to 41% of the neurons contained at least one megabase-scale de novo CNV (6). Additional studies, which analyzed fewer neuronal genomes, confirmed that de novo CNVs occur in at least 10% of neurons (7, 8). CNVs can be shared by multiple neurons and inherited in a clonal manner (8). Furthermore, megabase-scale CNVs typically alter the copy number of 10 or more genes in individual neurons. In addition to expression-level differences that can accompany gene copy number changes, mosaic neuronal CNVs also are expected to reveal or abate pernicious alleles on a neuron-by-neuron basis in every individual.
