Fig. 1
Genomic rearrangements with different levels of complexity. At the array-resolution level, genomic rearrangements with the PLP1 gain can be apparently simple as a a single duplication or b a CGR. In aCGH figures, transitions of copy number alterations from copy neutral regions (black dots) to copy number gains (red dots) are demonstrated by gray vertical dashed arrows (breakpoints). At the nucleotide sequence level as shown in a, in the simplest case scenario, a single duplication has a breakpoint junction with only one join-point (a—left), a product of one TS by NHEJ (for blunt end), or microhomology and/or microhomeology-mediated rearrangement. Or, a breakpoint junction can contain several join-points (a—right). Such breakpoint junctions are products of iterative TS by different rearrangement mechanisms such as NHEJ or MMBIR. Bases indicated in red are in both the proximal and distal reference sequences. Rectangle with diagonal lines indicates a region of imperfect match between proximal and distal reference sequences. In addition to the iterative TS that lead to the appearance of complex breakpoints, iterative TS can result in copy number transitions of large genomic segments and formation of more complex genomic structures. b As a representative of such complex genomic structures, a schematic figure of a CGR with DUP-TRP/INV-DUP pattern resulted from two TSs creating breakpoint junctions Jct1 and Jct2, as shown. The horizontal bar below the aCGH depicts the rearrangement product. Duplications are represented in red and triplication in blue; yellow arrows represent inverted low copy repeats that mediate the TS in Jct1. Positions of the genomic segments are denoted as a, b, and c, duplicated segments as a′, b′, and c′, and the triplicated segment as b″. The TS between low copy repeats forming Jct1 switched the direction of replication resulting in an inversion of the TRP segment, and the second TS forming Jct2 switched the direction of the replication again resulting in directly oriented DUP segments. The Y-axis on the aCGH plots represents expected log2 ratios in male using a gender-matched control and that PLP1 maps to chromosome X. Jct: junction; JP: join-point