Long interspersed element-1s (LINE-1s or L1s) can mobilize (i.e., retrotranspose) within the brain, leading to another form of somatic variation (42). Active L1s encode two proteins, ORF1p and ORF2p, which are required for retrotransposition. ORF2p contains endonuclease and reverse transcriptase activities that are needed to “copy-and-paste” L1 sequences into a new genomic location by a mechanism termed target-site primed reverse transcription (TPRT) (42, 43). In addition to canonical TPRT, L1s occasionally can integrate into endogenous DNA lesions (44). Moreover, recombination events that arise either during (15, 45–47) or after L1 retrotransposition (48) can lead to the formation of structural variants.
