Application and Prospects of Long-Read Sequencers for Preimplantation Genetic Testing for Structural Rearrangements

Long-read sequencers are known for their effectiveness in detecting genomic structural variations (SV) and are becoming a standard approach for comprehensive genetic analysis. In preimplantation genetic testing (PGT) for SV carriers, information on breakpoint junctions is required to determine the carrier status in embryo selection. Long-read sequencers are employed for SV cases that are difficult to analyze with conventional cytogenetical methods and the detailed SV junction information they provide yields valuable insights. They can also analyze the single-nucleotide variations (SNVs) that surround SVs and thus provide further information on the carrier status for embryo selection. Despite these advantages of long-read sequencers however, they are prone to inaccuracy and have high testing costs. This review summarizes the advanced applications of long-read sequencers currently in preclinical workups and their integration into PGT. It also presents in-house clinical cases that highlight long-read sequencing in practice and discusses the prospects for this field.