The Dutch Radboudumc claims to be the first hospital in the world to implement a new, powerful genetic test on a large scale within the clinic. The technology, based on long-read genome sequencing, promises a breakthrough in the diagnosis of rare disorders: faster, more efficient and with a significantly higher chance of a conclusive diagnosis. Whereas patients with a rare disease often go from one test to another for years, this new approach can finally offer clarity for a significant proportion of them.
In the case of rare disorders, doctors and laboratories search for genetic causes in the DNA. This is a complex puzzle, as the human genome consists of approximately six billion building blocks. Until now, DNA has been examined by reading it in very small fragments. This method is accurate, but limited in detecting complex abnormalities. Long-read sequencing changes that. This technique reads DNA in pieces that are many times larger, making it easier and much more complete to put the puzzle together.
5,000 tests per year
Radboudumc is starting with around 5,000 tests per year. These account for approximately one-sixth of all genetic analyses. The first applications focus on hereditary forms of blindness and severe intellectual disabilities. Research has already shown that the new technique allows DNA to be mapped much more completely than with the short-fragment method. ‘And that results in more than ten percent extra diagnoses for various rare conditions,’ says Professor of Genomic Technologies Alexander Hoischen. ‘In addition, based on all that completely measured DNA, we can detect new hereditary causes for certain conditions. This means that the percentage of extra diagnoses through research can increase further, up to fifteen percent.’
The technology also makes it possible to see genetic abnormalities that remain hidden with traditional methods. For example, long reads detect DNA fragments that have ended up on the wrong chromosome or larger structural variants that were previously invisible. According to Lisenka Vissers, Professor of Translational Genomics, this is crucial: “Sometimes, for example, a piece of DNA has been copied to the wrong chromosome. With long reads, we can see that much more easily,” says Professor of Translational Genomics Lisenka Vissers.
Rapid diagnosis is of great importance
The impact on patients and their families is significant. Professor Wendy van Zelst-Stams, head of the Genetics department at Radboudumc and MUMC+, emphasises the importance of rapid diagnosis: “It often ends years of uncertainty. A diagnosis provides insight into the course of a disease, helps parents make informed decisions about having children and brings families into contact with others in similar situations.”
The new technology also offers advantages for the laboratory. Because one comprehensive test can replace up to fifteen separate diagnostic tests, the process becomes more efficient, simpler and less prone to error. Helger IJntema, head of the Genome Diagnostics Laboratory, therefore calls the introduction a major step forward. ‘Long-read sequencing can replace fifteen other genetic tests in the clinic, making diagnostics faster and more efficient.’ Hoischen expects long-read genome sequencing to become the new international standard in genetic diagnostics.
