A recent study conducted by researchers from the Wellcome Sanger Institute, along with collaborators from the University of Exeter and the University of Cambridge, has shown that a single genetic test could potentially replace the current two-step approach to diagnosing rare developmental disorders in children. This shift could lead to earlier diagnoses for families and save the NHS vital resources. The study, published in Genetics in Medicine, involved reassessing genetic data from nearly 10,000 families from the Deciphering Developmental Disorders study. Researchers found that using exome sequencing, which reads only protein-coding DNA, is as accurate, if not better, than standard microarrays at identifying disease-causing structural genetic variations.
Changes in genetic code can range from single letter changes to the deletion or duplication of larger stretches of DNA, known as copy number variations (CNVs). While these variations can sometimes cause neurodevelopmental disorders, they can be harder to detect and understand in sequencing data. Currently, children suspected to have genetic diseases from these large deletions or duplications go through a lengthy process of testing and waiting for results from multiple diagnostic approaches. In this new study, a single approach was developed to detect these structural changes using data available from genome-wide exome sequencing assays. By combining four algorithms using machine learning methods, the researchers were able to develop a single-assay approach.
The new single-assay approach was able to reliably detect 305 large-scale pathogenic mutations, including 91 not previously detectable using standard clinical microarrays. The findings suggest that this new approach could potentially replace the current methods currently used in clinical practice. Caroline Wright, Professor of Genomic Medicine at the University of Exeter and author of the study, stated that using exome sequencing data to detect both large-scale changes and small genetic variants marks a significant step forward in making genetic testing simpler, cheaper, and more accessible. Helen Firth, Professor of Clinical Genomics at the University of Cambridge and lead clinician on the study, shared that the current system often involves children undergoing a lengthy process of different genetic tests before reaching a diagnosis, but this research brings hope for a future where families might only need one test.
Professor Matthew Hurles, Director of the Wellcome Sanger Institute and senior author of the study, emphasized the importance of understanding how large-scale genetic variations impact human health. With the right computational methods, a single test can accurately detect these variations, supporting its widespread adoption in NHS clinical practice. While this new approach offers hope for faster and more accurate diagnoses of rare genetic diseases and potential cost savings for the NHS, researchers also noted that more training is needed for specialists to generate and analyze the data effectively. This study highlights the potential for a significant shift in genetic testing practices, streamlining the diagnostic process for rare developmental disorders and improving outcomes for families and healthcare providers alike.
