Abstract
Genomic structural variants, including translocations, inversions, insertions, deletions, and duplications, are challenging to be reliably detected by traditional genomic technologies. In particular, balanced translocations and inversions can neither be identified by microarrays since they do not alter chromosome copy numbers, nor by short-read sequencing because of the unmappability of short reads against repetitive genomic regions. The precise localization of breakpoints is vital for exploring genetic causes in patients with balanced translocations or inversions. Long-read sequencing techniques may detect these structural variants in a more direct, efficient, and accurate manner. Here, we performed whole-genome, long-read sequencing using the Oxford Nanopore GridION sequencer to detect breakpoints in six balanced chromosome translocation carriers and one inversion carrier. The results showed that all the breakpoints were consistent with the karyotype results with only ~10× coverage. Polymerase chain reaction (PCR) and Sanger sequencing confirmed 8 out of 14 breakpoints; however, other breakpoint loci were slightly missed since they were either in highly repetitive regions or pericentromeric regions. Some of the breakpoints interrupted normal gene structure, and in other cases, micro-deletions/insertions were found just next to the breakpoints. We also detected haplotypes around the breakpoint regions. Our results suggest that long-read, whole-genome sequencing is an ideal strategy for precisely localizing translocation breakpoints and providing haplotype information, which is essential for medical genetics and preimplantation genetic testing.