Illumina’s Constellation Mapped Read Technology Reveals Hard-to-Detect Genomic Variants in GeneDx Pilot Study
San Diego, October 17, 2025 — Illumina, Inc. (NASDAQ: ILMN), a global leader in genomics technology, announced promising results from a pilot study conducted by GeneDx, a leader in genetic testing for rare diseases. The study evaluated Illumina’s emerging constellation mapped read technology, which demonstrated remarkable accuracy and speed in identifying complex genomic regions that have traditionally been challenging to analyze with short-read sequencing methods.
Unlocking Hidden Genomic Insights
GeneDx employed Illumina’s constellation technology to analyze 160 DNA samples from individuals diagnosed with known genetic diseases. Utilizing their fleet of NovaSeq X Plus Systems equipped with constellation kits, GeneDx compared results against various orthogonal techniques, including long-read sequencing, microarrays, and multiplex ligation-dependent probe amplification (MLPA).
The constellation technology excelled in detecting biologically significant, difficult-to-map variants, even outperforming these established orthogonal methods. Key findings included accurate identification of:
- Repeat expansions in the DMPK gene, linked to myotonic dystrophy.
- Variants in SMN1, pertinent to spinal muscular atrophy, despite the gene’s high similarity to the homologous SMN2 gene.
- Variants in NCF1, associated with chronic granulomatous disease, a challenging gene to analyze due to highly homologous pseudogenes.
- Mosaic aneuploidy, which involves chromosomal abnormalities in a subset of cells and is associated with developmental delays and certain childhood cancers.
Joe Devaney, Director of Laboratory Innovation at GeneDx, presented these early findings at the American Society for Human Genetics (ASHG) Annual Meeting in Boston. He highlighted that constellation technology’s combination of speed, simplicity, and scientific rigor offers new pathways for understanding and diagnosing rare and complex diseases with increased precision.
How Constellation Technology Works
Illumina’s constellation mapped read technology builds on the company’s longstanding sequencing-by-synthesis chemistry but innovates through enabling long-range genomic insights with streamlined workflows. Unlike traditional methods that rely on fragmented DNA, constellation applies long, unfragmented DNA molecules directly onto the flow cell for cluster generation. This eliminates manual library preparation steps and reduces validation needs.
Sophisticated informatics tools analyze the proximity of neighboring clusters on the flow cell to reconstruct long-distance genomic information. This approach facilitates confident mapping of homologous or repetitive DNA regions and resolution of complex structural variants that have historically posed analytical challenges.
Advancing the Future of Genomic Medicine
Steve Barnard, Illumina’s Chief Technology Officer, emphasized the technology’s potential to drive the genomics field into a new era of multiomics, enhancing rare disease diagnosis and treatment options. "Genomic insights remain critical to advance diagnosis and treatment for many rare and complex diseases, and our constellation technology provides the research insights that enable our customers to tackle these challenging conditions on the platforms they already use," Barnard stated.
GeneDx is exploring broader applications of the technology, noting its compatibility with diverse sample types such as buccal swabs, blood, and prenatal chorionic villus samples.
Devaney added, “Innovation and patient centricity fuel everything we do at GeneDx. The level of detail we can achieve with constellation provides promising insight into some of the world’s most complex and difficult-to-diagnose diseases. By combining speed, simplicity, and scientific rigor, this technology has the potential to transform how we understand rare disease, helping improve how we diagnose and treat patients.”
Commercial Availability and Future Directions
First introduced at the 2024 ASHG conference, Illumina’s constellation technology is slated for its first commercial release in the first half of 2026, fully compatible with the NovaSeq X Series sequencers.
GeneDx’s expanded study results were shared during a dedicated session at ASHG on October 15, 2025. The presentation, titled “Mapping the Future of Whole Genome Sequencing with Illumina Constellation Technology,” highlighted the technology’s ability to resolve genomic complexities unreachable by previous approaches.
About Illumina
Illumina advances human health by enabling comprehensive genome analysis. With a robust portfolio of DNA sequencing and array technologies, Illumina supports research, clinical, and applied markets worldwide. Their innovations contribute to progress in life sciences, oncology, reproductive health, agriculture, and emerging sectors. More information is available at illumina.com.
About GeneDx
GeneDx (Nasdaq: WGS) is a pioneering genetic testing company focusing on rare diseases. Combining extensive clinical expertise with advanced genomic technologies and the largest rare disease database – GeneDx Infinity™ – the company provides clinicians high-confidence diagnostic solutions. GeneDx is committed to transforming healthcare by integrating genomics into proactive patient care. Further details can be found at genedx.com.
Source: PR Newswire
