Structural variant formation at common fragile sites by svCapture

Large, actively transcribed common fragile site (CFS) genes are hotspots for genomic instability. svCapture exploits this instability and error-corrected sequencing as a reliable method for detecting rare structural variant (SV) junctions. We used svCapture to enrich whole genomic DNA sequencing reads near the middle of two CFS genes in two publicly accessible human cell lines: genes FHIT and WWOX in lymphoblastoid line GM12878 and colon cancer line HCT116. Results reveal the distribution and nature of SV formation at these genes under replication stress induced by low doses of aphidicolin (APH) and in conditions and derivative cells lines where mitotic DNA synthesis (MiDAS), DNA polymerase theta (POLQ) and canonical nonhomologous end joining (c-NHEJ) were impaired. Flow sorting of cells reveal SV formation as a function of cell cycle.