A newly implemented genetic testing approach is now being used in clinical practice to support the diagnosis of rare diseases. This method is designed for large-scale clinical use and offers faster and more comprehensive diagnostic results compared with currently used methods. It has the potential to simplify the diagnostic process by replacing multiple existing diagnostic techniques.
This genetic test is based on long-read genome sequencing. This technique analyzes an individual’s entire DNA, approximately 6 billion building blocks/cell, to identify possible hereditary causes of disease. Unlike traditional methods that sequence short fragments, long-read sequencing works with larger DNA segments, similar to completing a jigsaw puzzle with bigger pieces. This is making the assembly process more comprehensive and accurate. Previously, the technical limitations of long-read sequencing restricted its clinical use, but advances have made it feasible and reliable for diagnosis.
According to experts in translational genomics, long-read sequencing improves the identification of certain types of genetic variation, such as DNA segments that may be misplaced or incorrectly copied to other chromosomes. The method can also detect epigenetic modifications, including chemical markers that switch genes on or off, and provide important additional details regarding the underlying cause of a rare condition.
Research findings indicate that long-read genome sequencing offers a more complete representation of the genome compared with traditional short-read methods. Early data suggest that this technique may increase diagnostic yield by more than 10% for individuals with rare diseases. Further analyses also indicate that obtaining a full and precise map of an individual’s DNA may reveal new hereditary disease mechanisms. This is potentially increasing diagnostic rates by up to 15% through research settings.
Clinicians note that this test is particularly useful for identifying genetic abnormalities that are difficult to detect using existing diagnostic techniques. For many patients and families, achieving a genetic diagnosis can provide clarity, help guide expectations, connect individuals with others experiencing the same condition, and allow for assessing risks for families considering children.
This testing method will initially be conducted on around 5,000 tests per year, representing roughly one-sixth of their annual analyses, focusing on genetic forms of severe intellectual disabilities and blindness. Its implementation is supported by a multidisciplinary team specializing in genome diagnostics. Experts anticipate that long-read sequencing may eventually become the primary new standard method used in routine genome-based diagnostics.
Reference: Radboudumc University Medical Center. World first: Radboudumc pioneers new genetic test in clinical practice. Published November 17, 2025. Accessed November 18, 2025. World first: Radboudumc pioneers new genetic test in clinical practice – New test is faster, more efficient, and provides more diagnoses for rare diseases – Radboudumc
