Subtitle: How cutting-edge genome analysis is transforming our understanding of Parkinson’s and related disorders
When it comes to unraveling the complexities of Parkinson’s disease, genetics is center stage. Scientists long suspected that the architecture of this intricate neurodegenerative disorder is built upon contributions from both rare, dramatic DNA changes and a tapestry of common, subtler variants. But as technology has evolved, so has our ability to detect—and interpret—these hidden genomic nuances.
For years, short-read DNA sequencing technologies were the workhorses of genetic research. While revolutionary in many ways, these technologies can struggle to accurately map out certain regions of the genome—especially those featuring complex structural variants, long stretches of repeated DNA, or the intricacies of how maternal and paternal gene versions (known as haplotypes) interact. All these details can be crucial when it comes to explaining why and how people develop Parkinson’s, or even how they might respond to treatment.
Enter long-read sequencing. Platforms like Oxford Nanopore Technologies now give researchers the ability to read much longer stretches of genetic code in one go. This technological leap is reshaping the landscape of Parkinson’s genomics—and with it, hope for advances in diagnosis, prognosis, and therapy.
Why Are We Missing Hidden Variants?
Short-read sequencing, typically capturing bits of genetic material just a few hundred base pairs long, often fails to see the whole picture. Large structural variants—such as duplications, deletions, and repeat expansions—can evade detection, remaining invisible to traditional approaches. These mutations, however, may have a substantial impact on disease development or progression, making their identification vital.
Moreover, the phase of genetic variants—knowing how different mutations are inherited together—can be missed, obscuring critical insights about familial risk and disease modification. Because Parkinson’s can be linked to both rare, high-impact mutations and more common, polygenic risk factors, a complete view is paramount for decoding the interplay of genes involved.
The Promise of Long-Read Sequencing
With long-read sequencing, researchers are now able to access previously hidden parts of the human genome. The technology sequences DNA in much longer fragments—sometimes tens of thousands of base pairs—enabling them to smoothly bridge areas rife with complex repeats and structural variants. In doing so, long-read sequencing technologies are illuminating corners of the human genome that were, until now, impenetrable to researchers.
A recent webcast, sponsored by Oxford Nanopore Technologies, brought together leading experts in the field to discuss these advances. Among them was Professor Joanne Trinh, an authority at the Institute of Neurogenetics, University of Luebeck. Trinh’s group is focused on “integrative omics” approaches to Parkinson’s, blending genetic, molecular, and environmental data to understand both rare monogenic and more common forms of the disease.
Dr. Michael Jansen, a Senior Field Application Scientist at Oxford Nanopore Technologies, highlighted how this new approach enables deeper exploration of the genetic features that underlie Parkinson’s and similar movement disorders. With his extensive background in gene transfer and application of genomics technologies, Jansen detailed the technical and practical leaps made possible by long-read sequencing.
New Insights, New Questions
The application of long-read sequencing in Parkinson’s research is yielding exciting results. Researchers are now identifying novel variations—types of genetic changes never picked up before. These include complex rearrangements, expansions in DNA repeat regions, and the ability to map out haplotypes with much greater precision. Such discoveries not only refine our understanding of who develops Parkinson’s and why, but may also clarify distinctions between different Parkinson’s subtypes.
Just as importantly, these findings are poised to transform strategies for diagnosis and patient stratification. Knowing which variants are present—and how they may interact—can help clinicians better predict the course of the disease for individual patients. This could, in turn, inform more tailored monitoring protocols, treatments, or even preventive strategies for those at risk.
Looking Ahead: Precision Neurology
While the current pace of discovery is exhilarating, researchers emphasize the importance of continued vigilance and innovation. Much remains to be explored—including how genetic features identified by long-read sequencing interact with environmental factors like toxins or lifestyle. The hope is that, through integrating newly-discovered genomic data with clinical and molecular information, scientists can move from merely understanding risk to actually altering disease trajectories.
Events such as the recent webcast, featuring expertise from leaders in neurogenomics and molecular technology, serve as key touchpoints for sharing discoveries and accelerating clinical impact. As more researchers adopt long-read sequencing in their work, expect even more hidden aspects of Parkinson’s—and related neurological disorders—to emerge.
For patients, families, and clinicians, these advances represent hope. While Parkinson’s remains a complex puzzle, new tools like long-read sequencing are finally helping us fit more of the pieces together.
Reference:
Nature. (2024). Revealing hidden genomic variation in Parkinson’s and related disorders. https://www.nature.com/articles/d44224-025-00029-3
