Hi-C–Based 3D Genome Mapping Tool Exposes Hidden Structural Variants in Clinical Study

Overview

• The peer-reviewed Journal of Molecular Diagnostics study evaluated genomic proximity mapping on DNA from 123 patients with suspected genetic disorders.
• The assay matched 137 previously identified large variants with 100% concordance, covering 110 copy-number changes and 27 rearrangements.
• Investigators also found 12 previously undetected structural variants and uncovered cryptic complexity, including a case with 13 breakpoints across four chromosomes.
• Breakpoints were localized to about 10 kb, with successful detection in preserved tissue and sensitivity to low-level mosaicism.
• The method uses less input DNA than optical genome mapping or long-read sequencing, though broader clinical adoption awaits further validation and integration; a Phase Genomics employee is a co-author.