Recent studies revealed that mosaic neuronal genomes are the rule, rather than the exception; every neuron probably has a different genome than the neurons with which it forms synapses. Not unexpectedly, SNVs are the most prevalent somatic mutations. A “triple calling” strategy was used to identify and validate clonal SNVs in MDA-amplified DNA from single neurons isolated from a neurotypical brain, leading to estimates of ~1000 to 1500 SNVs per neuronal genome (5). By comparison to human cortical neurons, a SCNT experiment in reprogrammed mouse olfactory neurons detected hundreds of SNVs per neuron and a lower proportion of C-to-T transition mutations (84). Although the divergent SNV rates between these two studies may arise from technical differences (as discussed above), both approaches establish that SNVs represent an important form of somatic mutation in both human and mouse neurons.
