Large Inverted Duplications in the Human Genome Form via a Fold-Back Mechanism

摘要: Inverted duplications are a common type of copy number variation (CNV) in germline and somatic genomes. Large that include many genes can lead to both neurodevelopmental phenotypes children gene amplifications tumors. There several models for inverted duplication formation, most which dicentric chromosome intermediate followed by breakage-fusion-bridge (BFB) cycles, but the mechanisms give rise remain unknown. Here we have combined high-resolution array CGH, custom sequence capture, next-generation sequencing, long-range PCR analyze breakpoints 50 nonrecurrent patients with intellectual disability, autism, congenital anomalies. For half rearrangements our study, sequenced at least one breakpoint junction. Sequence analysis junctions reveals normal-copy disomic spacer between non-inverted copies duplication. Further, short sequences present boundary These data support mechanism formation whereby double-strand break intrastrand pairs itself form “fold-back” that, after DNA replication, produces corresponding site fold-back loop. This process adjacent terminal deletions, juxtaposed translocations, ring chromosomes.