Errors incurred during DNA replication or transcription also can lead to the formation of CNVs. Large, actively transcribed genes that undergo replication during late S-phase correspond to chromosomal fragile sites and are hot spots for the generation of genomic variants and translocations (37, 38). Because neuronal genes are overrepresented among the longest genes in the human genome, transcription may predispose these genes to somatic CNVs (39). Indeed, intragenic deletions within large, neuronally expressed genes (e.g., AUTS2, IMMP2L, NXRN1, and CNTNAP2) are associated with ASD, intellectual disability, and other neurodevelopmental disorders (40, 41). Thus, if individuals harbor somatic CNVs at these loci in many neurons or in neurons within specific functional brain regions, they may be susceptible to neurological disease.
