Complex Genomic Rearrangements at the Locus Include Triplication and Quadruplication

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Genomic architecture, such as direct or inverted repeats, can facilitate structural variation (SV) of the human genome. SV can consist of deletion, duplication, or inversion of a genomic segment, or combinations thereof, the latter referred to as complex genomic rearrangements (CGR). CGR are defined as requiring two or more novel DNA breakpoint junctions. We described a CGR product at the MECP2 locus with an unusual pattern consisting of an inverted triplicated segment flanked by duplicated segments of the genome. This complex CGR is facilitated by inverted repeats in a process that mechanistically could occur by two template switches mediated by replicative DNA repair. We now investigate the PLP1 locus and demonstrate that 16/17 CGR independent events present with duplication—inverted triplication—duplication pattern facilitated by two inverted repeats, similar to events involving MECP2. We show that the same inverted repeats facilitating CGR formation are also responsible for an inversion polymorphism observed frequently in the normal population. Intriguingly, one CGR was found to have a quadruplication resulting in the presence of four copies of a genomic segment. Breakpoint studies suggest this quadruplication occurred in a manner consistent with rolling circle amplification as predicted by previously postulated models.

Vyšlo v časopise: Complex Genomic Rearrangements at the Locus Include Triplication and Quadruplication. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005050
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005050

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