Neurons with Complex Karyotypes Are Rare in Aged Human Neocortex

Neocortical neurons are among the most diverse and longest-lived mammalian cells, and human-specific brain phenotypes are attributed to neocortical expansion during evolution. McConnell and coworkers assembled a brain copy number variation (CNV) atlas to reveal the frequency of neocortical neurons with complex karyotypes and the associated variability among individuals. These CNVs represent rare variants with strong contributions to genetic risks for schizophrenia, autism, and other neurological disorders. The CellRaft® Technology was used to isolate, and verify the integrity of, single nuclei following flow sorting to assess the quality of the whole genome amplification (WGA) method utilized. The authors provide evidence that a functional consequence of CNV neurons may be selective vulnerability to aging-associated atrophy.