NHEJ occurs as a result of the aberrant repair of DNA double strand breaks and is guided entirely by the information contained within or near the DNA lesion for repair, which makes it error prone as compared to NAHR (Lieber, 2008) (Figure 2B). The breakpoints of CNVs formed by NHEJ are frequently observed within repetitive elements, such as long terminal repeats (LTRs), short interspersed repeat elements (SINEs), long interspersed nuclear elements (LINEs), and mammalian interspersed repeats (MIRs). This suggests that NHEJ may be stimulated by certain genomic architectures, but extensive sequence homology is not required (Toffolatti et al., 2002). Breakpoints of some non-recurrent deletion CNVs have sequences with very short (2–20 basepairs) stretches of nucleotide identity. These are predicted to be formed by an alternative microhomology mediated end joining (MMEJ) mechanism (Lieber, 2010).
