NAHR involves the alignment and subsequent crossing over between two sites in the genome that share region of sequence homology (Figure 2A). NAHR can occur both in meiosis (Turner et al., 2008) and, at lower frequency, in mitotically-dividing cells as well (Lam and Jeffreys, 2006, 2007). NAHR can involve genomic rearrangements between paralogs on homologous chromosomes (interchromosomal), sister chromatids (interchromatid), and within chromatid (intrachromatid) (Gu et al., 2008). The relative positions and extent of these homologies influence the rate of NAHR events (Liu et al., 2011b). Regions of the genome that possess tandemly-arranged segmental duplications (SDs), which are also called low copy repeats (LCRs), are more prone to frequent rearrangements between specific LCRs due to NAHR. As a result, multiple rearrangements, which are nearly identical to each other, can arise independently in different individuals (Gu et al., 2008). Such recurrent de novo CNVs can occur at rates as high as 1/4,000 newborns (Devriendt et al., 1998).
