It is hard to believe that all the cells of a human brain share identical genomes. Indeed, single cell genetic studies have demonstrated intercellular genomic variability in the normal and diseased brain. Moreover, there is a growing amount of evidence on the contribution of somatic mosaicism (the presence of genetically different cell populations in the same individual/tissue) to the etiology of brain diseases. However, brain-specific genomic variations are generally overlooked during the research of genetic defects associated with a brain disease. Accordingly, a review of brain-specific somatic mosaicism in disease context seems to be required. Here, we overview gene mutations, copy number variations and chromosome abnormalities (aneuploidy, deletions, duplications and supernumerary rearranged chromosomes) detected in the neural/neuronal cells of the diseased brain. Additionally, chromosome instability in non-cancerous brain diseases is addressed. Finally, theoretical analysis of possible mechanisms for neurodevelopmental and neurodegenerative disorders indicates that a genetic background for formation of somatic (chromosomal) mosaicism in the brain is likely to exist. In total, somatic mosaicism affecting the central nervous system seems to be a mechanism of brain diseases.
Keywords: Aneuploidy; Brain; Chromosome instability; Copy number variations; Gene mutations; Genome instability; Somatic mosaicism.
© 2022. The Author(s).