GeneDx's early results illustrate the ability of constellation to rapidly identify hard-to-detect variants implicated in rare disease. GeneDx's Director of Laboratory Innovation Joe Devaney will present on the company's early experiences with the constellation technology today at the American Society for Human Genetics (ASHG) Annual Meeting in Boston.
"Illumina is unlocking ways to access the most difficult regions of the genome, as we simultaneously lead the industry into a new era of multiomics," said Steve Barnard, chief technology officer of Illumina. "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."
For the pilot project, GeneDx used its fleet of NovaSeq X Plus Systems with constellation kits to evaluate 160 DNA samples from individuals with known genetic disease. GeneDx compared samples run with constellation to orthogonal methods, like long-read sequencing, arrays, and multiplex ligation-dependent probe amplification. Constellation was able to accurately uncover repeat expansions, complex structural variants, and elusive regions of the genome, demonstrating the technology's ability to meet or exceed the capabilities of established alternative methods.
Constellation was able to quickly identify difficult-to-detect, biologically relevant variants, including those in:
- DMPK, which is associated with myotonic dystrophy and is caused by large repeat expansions;
- SMN1, which is associated with spinal muscular atrophy but is difficult to detect based on the highly homologous SMN2 gene;
- NCF1, which is associated with an inherited immune disorder called chronic granulomatous disease, but is challenging to identify due to highly homologous pseudogenes; and
Mosaic aneuploidy, which causes some cells to have chromosomal abnormalities. It can cause developmental delays and increase the risk of some childhood cancers.
Deep and rapid insights from whole-genome sequencing can help researchers understand and better identify potential treatments for these hard-to-diagnose conditions. Constellation is emerging as a flexible solution that performs accurately across a variety of sample types—including buccal, blood, and chorionic villus (prenatal) samples—and extraction kits.
"Innovation and patient centricity fuel everything we do at GeneDx," said Devaney. "We're continually looking to advance research and clinical genomics to drive the future of precision medicine and better health outcomes for all. 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."
How constellation mapped read technology works
Constellation builds on Illumina's industry-leading sequencing-by-synthesis chemistry to unlock long-range genomic insights with unmatched simplicity. Long sequences of unfragmented DNA are applied directly to the flow cell for cluster generation. This on-flow-cell library prep eliminates manual library preparation and enables a streamlined workflow with fewer validation steps. Proprietary informatics extract long-distance data from the proximity of resulting neighboring clusters. This novel data allows for accurate mapping of homologous or repetitive regions of the genome, resolving mapping ambiguities, and resolving complex variant types.
About Illumina
Illumina is improving human health by unlocking the power of the genome. Our focus on innovation has established us as a global leader in DNA sequencing and array-based technologies, serving customers in the research, clinical, and applied markets. Our products are used for applications in the life sciences, oncology, reproductive health, agriculture, and other emerging segments.
About GeneDx
GeneDx (Nasdaq: WGS) is the global leader in rare disease diagnosis, transforming the way medicine is practiced by making genomics the starting point for health, not the last resort. We bring together unmatched clinical expertise, advanced technology, and the power of GeneDx Infinity™ – the largest rare disease dataset – built over 25 years from millions of genomic tests and deep clinical insights. This unparalleled foundation powers our ExomeDx™ and GenomeDx™ tests, giving clinicians the highest likelihood of delivering a timely, accurate diagnosis. GeneDx is shaping the future of healthcare by moving the standard of care from sick care to proactive healthcare. While our roots are in rare disease diagnosis, our commitment extends beyond – growing with the families we serve – as a trusted partner at every stage of life.
For more information, please visit www.genedx.com
