Traditional genetic tests analyse DNA in a one-dimensional way, often missing crucial, disease-causing structural changes. A study in The Journal of Molecular Diagnostics introduces a new method called Genomic Proximity Mapping (GPM), poised to transform diagnostics by reliably revealing these hidden variants.
The technique, GPM is a Hi-C based assay that captures the spatial relationships and folding patterns of DNA within the nucleus. This capability allows it to detect copy-number changes and rearrangements that are invisible to linear sequencing.
Researchers applied GPM to DNA from 123 individuals with suspected genetic disorders. Results showed 100% concordance in detecting all 110 known deletions/duplications and 27 rearrangements. Significantly, GPM uncovered 12 novel structural variants that standard clinical tests had missed. In every case with complex rearrangements, GPM found additional cryptic changes, such as locating 13 breakpoints across four chromosomes in a single patient. It also successfully detected low-level mosaic variants.
GPM requires substantially less DNA than conventional methods and works with challenging samples, enhancing its practicality for clinical use. This high-resolution characterisation will improve precision diagnostics, allowing doctors to provide more personalised treatment and better prognosis.
Image Credit: The Journal of Molecular Diagnostics (2025). DOI: 10.1016/j.jmoldx.2025.07.005 (MedicalXpress)
Article can be accessed on: MedicalXpress
