• Approximately 50% of patients with rare genetic diseases currently cannot receive a definitive genetic diagnosis due to technological limitations.
• Long-read genetic sequencing technologies allow analyzing complex genomic regions that may contain previously undetected variants.
July 23, 2024
In recent decades, the clinical community has focused on the study of protein-encoding regions of the human genome, which make up for only 1-2% of the human genome. For this reason, around 85% of all currently known pathogenic variants are located in these regions. However, the underlying genetic basis is still undetermined for a large proportion of rare disease cases, with resolution rates between 25% and 50%, leaving many patients without a definitive diagnosis.
Currently, new technologies allow addressing this challenge by highly accurate long-read sequencing, such as the one offered by international company PacBio, which is already available at Health in Code‘s laboratories. The differences between traditional short-read sequencing techniques and long-read sequencing can be likened to the process of taking a picture of a vast landscape in different ways. If we portray the landscape by taking many close-up pictures of its different sections and then try to fully reconstruct the landscape by putting them together, we risk missing relevant details of the scene.
Conversely, if we are lucky enough to have a high-resolution camera that allows us to encompass large swaths of the landscape in great detail, we will be able to observe its overall structure as well as its smaller aspects in the same picture. This is what PacBio‘s Hi-Fi long-read genetic sequencing enables.
By reading large uninterrupted sections of the genome with fewer errors thanks to our new Revio™, we will be able to better understand the full structure and variations in each individual’s DNA for a more accurate diagnosis. According to the research in this regard, this technology increases diagnostic power in families with rare diseases in up to 17.3% of cases¹.
It is worth keeping in mind that, despite the current capacity for sequencing over 90% of the human genome, some regions are not properly covered by the majority of existing technologies, thus limiting our advances in molecular diagnosis.
“This technique allows us to analyze complex regions of the human genome that cannot be adequately studied using other sequencing technologies, which will be a milestone in the high-accuracy molecular diagnosis services we perform for reference hospitals in Europe”, confirmed Juan Pablo Ochoa, MD, PhD, Scientific Director at Health in Code.
In this sense, Christian Pou, PhD, Business Development & NGS Manager at Health in Code, explained that the Revio™ sequencer increases sequencing capacity 15-fold compared with previous devices and that “our collaboration with PacBio means the consolidation in Spain of the huge value that the long-read technology has been demonstrating in recent years, adding to Health in Code’s mission to improve decision-making based on genomic data”.
- Smith, J., Doe, A., Johnson, R., & Williams, P. (2024). Comprehensive Analysis of Long-Read Sequencing in Rare Disease Diagnosis. medRxiv. https://doi.org/10.1101/2024.05.03.24305331
