The genomically mosaic brain: Aneuploidy and more in neural diversity and disease

Genomically identical cells have long been assumed to comprise the human brain, with post-genomic mechanisms giving rise to its enormous diversity, complexity, and disease susceptibility. However, the identification of neural cells containing somatically generated mosaic aneuploidy – loss and/or gain of chromosomes from a euploid complement – and other genomic variations including LINE1 retrotransposons and regional patterns of DNA content variation (DCV), demonstrate that the brain is genomically heterogeneous. The precise phenotypes and functions produced by genomic mosaicism are not well understood, although the effects of constitutive aberrations, as observed in Down syndrome, implicate roles for defined mosaic genomes relevant to cellular survival, differentiation potential, stem cell biology, and brain organization. Here we discuss genomic mosaicism as a feature of the normal brain as well as a possible factor in the weak or complex genetic linkages observed for many of the most common forms of neurological and psychiatric diseases.

► Developing and mature brains are composed of cells that can be genomically varied and mosaic.
► Mosaic aneuploidy, as part of DNA content variation (DCV), along with their analyses in brain cells are described.
► Functions for neural genomic mosaicism are discussed; roles in cell death and survival implicate selection mechanisms.
► The relevance of mosaic genomic variation to neurological and psychiatric disorders is discussed.