A new 3D genome mapping method, genomic proximity mapping (GPM) via Hi-C based sequencing, can detect structural DNA variants that standard linear tests miss, including copy-number changes, rearrangements, and mosaic variants.

Co-lead investigator says GPM delivers high-resolution, comprehensive genomic characterization even from low-quality or archived tissue, supporting improved diagnostics, prognosis, and family counseling.

The study, published in The Journal of Molecular Diagnostics in 2025, suggests potential shifts in diagnostic testing and treatment for genetic disorders based on 3D genome organization.

Detecting exact genetic rearrangements with GPM could enable targeted therapies or clinical trials tailored to those specific variants, enhancing precision diagnostics and personalized treatment.

In 123 individuals with suspected genetic disorders, GPM identified all known large chromosomal variants with 100% concordance and uncovered 12 novel structural variants missed by conventional tests.

The study revealed hidden complexity in cases with multiple rearrangements, including cases where GPM mapped 13 breakpoints across four chromosomes instead of the initially suspected rearrangement.

GPM requires substantially less DNA than traditional cytogenetic methods and is more practical for clinical use than emerging technologies like optical genome mapping and long-read sequencing.