Application of optical genome mapping in accurate detection of cryptic balanced chromosomal translocations

To explore the clinical practicability of optical genome mapping in accurate detection of cryptic chromosomal balanced translocations (CBRT). A retrospective analysis was conducted on patients that visited the Jiangxi Maternal and Child Health Hospital from May 2023 to April 2024 and underwent copy number variation testing of embryos. OGM was performed on four couples with detected deletions/duplications in miscarried embryos but no abnormalities in karyotyping, and Nanopore sequencing was used for validation. OGM successfully detected four cases of CBRT, with the minimum size of translocation fragments reaching 46.86kb, of which, a t(2;6)(q37.3;q25.3) was detected using the T2T genome reference, not the GRCh38 reference. In addition, we identified four genes that were possibly disrupted by breakpoints, namely LINC01881、TRIM67、NECTIN1、CTAGE10P, which were verified by sequencing. In conclusion, optical genome mapping can accurately detect CBRT and locate the position of breakpoints. With the improvement of human reference genome and the reduction of cost, OGM will be more and more widely used in clinical practice.