A leader in genetic testing for rare diseases, GeneDx is successfully piloting emerging Constellation mapped read technology from Illumina to demonstrate the platform's superior ability to resolve difficult-to-map regions of the human genome.
GeneDx's early results, presented at the American Society for Human Genetics (ASHG) 2025 Annual Meeting, show that Constellation, which operates on the NovaSeq X Plus Systems, can rapidly and accurately identify challenging variants implicated in rare diseases, often outperforming orthogonal methods like long-read sequencing and arrays.
The pilot involved evaluating 160 DNA samples from individuals with known genetic diseases, where Constellation accurately uncovered complex variant types such as repeat expansions and structural variants in notoriously difficult genes. Specifically, the technology quickly identified biologically relevant variants in DMPK (associated with myotonic dystrophy), SMN1 (associated with spinal muscular atrophy), NCF1 (associated with chronic granulomatous disease), and mosaic aneuploidy. This innovation builds on Illumina's industry-leading sequencing-by-synthesis chemistry by applying long sequences of unfragmented DNA directly to the flow cell, eliminating manual library preparation and using proprietary informatics to extract long-distance data from neighboring clusters.
The simplified workflow allows for the accurate mapping of homologous or repetitive genomic regions, providing deep and rapid insights critical for advancing the diagnosis and treatment of complex conditions.
Illumina's Chief Technology Officer, Steve Barnard, highlighted that Constellation is key to unlocking the most difficult genomic regions on existing platforms, while GeneDx's Director of Laboratory Innovation, Joe Devaney, emphasized that the technology's combination of speed, simplicity, and scientific rigor has the potential to transform rare disease understanding and patient care. Following its introduction at the 2024 ASHG conference, the first commercially available Constellation product, compatible with the NovaSeq X Series, is slated for release in the first half of 2026.