Fig. 1. Schematic representation of low-copy repeat/nonallelic homologous recombination (LCR/NAHR)-based mechanisms for genomic rearrangements. Chromosomes are shown in black, with the centromere depicted by hashed lines. Yellow arrows depict LCRs. The figure depicts LCRs arranged horizontally according to orientation and structure (direct, inverted, complex). The chromosome rearrangements and predicted products of recombination are listed vertically by mechanisms (interchromosomal; intrachromosomal; and intrachromatid). Interchromosomal misalignment leads to deletion/duplication (directly oriented LCRs) (a) and inversion (inverted repeats) (b). Intrachromatid loop of inverted repeats results in inversion (h). Interchromatid mispairing of direct repeats results in deletion/duplication (d). Intrachromatid misalignment of directed repeats (g) can result in deletion and an acentric fragment. Inv dup(15) and inv dup(22) chromosomes can result from interchromosomal (c) or intrachromosomal (e) unequal exchange between inverted LCRs. Also complex LCRs can be responsible for deletion/duplication (f) or inversion (i).

Fig. 2. Rearrangement sizes in genomic disorders. The horizontal axis represents a scale of the human genome from 1 base pair (10⁰ bp) to 3 gigabase pairs (10⁹ bp); the size of the human genome. The size of the DNA rearrangement and the type of condition manifested are shown above. Note the rearrangements can span significant genomic distances. The condition manifested corresponds to the size of the genome segment involved and which genes are present within the rearranged segment.

Fig. 3. Complex structure of selected low-copy repeats (LCRs). Horizontal lines represent specific genomic regions with the centromere toward the left and telomere to the right. At the right are listed abbreviations for the disease manifested through common deletions of the regions. The colored regions refer to LCRs with the orientation given by the arrowhead. Note complex structure of LCRs consisting of both direct and inverted repeats. (a) LCRs in chromosome 2q13 responsible for rearrangements associated with familial juvenile nephronophthisis 1 (NPHP1). (b) LCRs7 flanking the Williams–Beuren syndrome (WBS) chromosome region 7q11.23. (c) LCRs15 within the Prader–Willi syndrome/Angelman syndrome (PWS/AS) chromosome region 15q11.2. (d) Smith–Magenis syndrome (SMS) repeats within 17p11.2. (e) LCRs22 within the DiGeorge syndrome (DGS) chromosome 22q11.2.

Table 1. Mendelian genomic disordersa

Table 2. Contiguous gene syndromes as genomic disordersa

Table 3. Recurrent constitutional chromosomal rearrangements as genomic disordersa