Identification of complex and cryptic chromosomal rearrangements by optical genome mapping

Abstract

Background Optical genome mapping (OGM) has developed into a highly promising method for detecting structural variants (SVs) in human genomes. Complex chromosomal rearrangements (CCRs) and cryptic translocations are rare events that are considered difficult to detect by routine cytogenetic methods. In this study, OGM was applied to delineate the precise chromosomal rearrangements in three cases with uncertain or unconfirmed CCRs detected by conventional karyotyping and one case with a cryptic translocation suggested by fetal chromosomal microarray analysis (CMA). Results In the three cases with CCRs, OGM not only confirmed or revised the original karyotyping results but also refined the precise chromosomal structures. In the case with a suspected translocation not detected by karyotyping, OGM efficiently identified the cryptic translocation and defined the genomic breakpoints with relatively high accuracy. Conclusions Our study confirmed OGM as a robust alternative approach to karyotyping for the detection of chromosomal structural rearrangements, including CCRs and cryptic translocations.

Optical Genome Mapping for Cryptic Chromosomal Rearrangements Identification in Clinical Practice

“…3,4 Here, we found that the high resolution of OGM makes it a promising method for detecting cryptic BCRs; our findings were in agreement with those of two other recent studies. 9,10 Detailed information about breakpoints is another superior characteristic of OGM when compared to karyotyping and FISH. 3,4 Although breakpoints identified by OGM were not directly validated using other methods, consistency with offspring rearrangements nevertheless underscored the reliability of OGM in identifying SV breakpoints.…”