Genomic technology is revolutionising the diagnosis and treatment of rare diseases. As advancements like whole-genome sequencing promise faster, more accurate diagnoses, experts are working to ensure equitable access to these life-changing tools for all.
Whole-genome sequencing is dramatically speeding up rare disease diagnoses. Photo: Thor Swift. © 2020
A child’s first symptoms appear suddenly—small, unexplainable changes that leave parents searching for answers. For many families, this search becomes an agonising odyssey, spanning years of inconclusive tests, incorrect diagnoses, and unanswered questions. But now, a revolution in genomic technology is rewriting the story of rare diseases, offering clarity and hope where uncertainty once prevailed.
When Professor Zornitza Stark, a Melbourne-based clinical geneticist at Australian Genomics, first encountered a child with an undiagnosed rare disease early in her career, the process of finding an answer was painfully slow. Genetic tests for single genes could take months or even years, and many families were left in limbo, uncertain about their future. Today, a revolution in genomic technology is changing that narrative, offering hope to millions living with rare diseases worldwide.
“We have seen firsthand how a fast and accurate diagnosis can change lives,” Stark says.
Across the globe, scientists and clinicians are harnessing whole-genome sequencing to transform the diagnosis and treatment of rare diseases. These advancements are not only solving medical mysteries that have confounded doctors for decades but also raising profound questions about equity, accessibility, and the future of precision medicine.
Genomic testing for rare diseases
There are more than 7,000 rare diseases that collectively impact more than 300 million people globally. Many rare diseases have a genetic origin, often caused by mutations in a single gene, while others may be caused by infections, environmental factors, or unknown causes. Because these conditions frequently lack widespread awareness and research funding, people often face significant challenges in obtaining an accurate diagnosis and accessing effective treatments.
Genomic testing, particularly whole-genome sequencing, has emerged as a revolutionary tool for diagnosing rare diseases. Whole-genome sequencing enables scientists to analyse the entire genetic blueprint of a person and compare it to a ‘reference genome’ made up of a combination of several people’s DNA. This allows them to identify mutations that might be causing disease.
Unlike traditional diagnostic methods that examine one gene at a time, whole-genome sequencing provides a comprehensive view of all human genes—of which there are about 20,000—which helps to dramatically reduce diagnostic time.
Long-read sequencing—more detailed analysis that sequences longer fragments of a person’s DNA— goes a step further, revealing variations that standard short-read sequencing often misses and thus improving diagnostic rates.
These technologies are not only shortening the diagnostic journey for people with rare diseases but are also paving the way for personalised treatment options and better overall patient outcomes.
“For patients, immediately, the effect will be that we will be able to help more of them with the diagnosis,” explains Christian Gilissen, a genome bioinformatics expert at Radboud University Medical Center in the Netherlands. “This will also have an immediate effect on the number of patients that we can potentially offer treatment to.”
Bringing genomics into clinical practice
Stark is at the forefront of integrating whole-genome sequencing into clinical practice. She has championed the use of whole-genome sequencing for diagnosing rare diseases in Australia by demonstrating that rapid genomic analysis can enable a concrete rare disease diagnosis in just days, replacing years of uncertainty.
In a landmark 2018 study, researchers demonstrated that whole-genome sequencing could diagnose genetic conditions in critically ill infants within 48 hours—a breakthrough that, in some cases, enabled life-saving interventions. The technology is particularly promising for newborn screening, where identifying a rare disease early could mean the difference between life and death.
“We identified a baby with a very serious underlying immunodeficiency who needed a bone marrow transplant. We were lucky to be able to do that before the baby became unwell,” Stark says.
Gilissen says whole-genome sequencing is particularly adept at picking up neurodevelopmental disorders such as Rett syndrome, fragile X syndrome, and Dravet syndrome. This is due to their genetic heterogeneity, which means that different gene mutations can cause the same disease or condition.
“Our goal is to make genomic sequencing a first-line diagnostic tool, accessible to every patient who needs it.”
While whole-genome sequencing is not yet universally accessible in Australia, national genomic alliances and funding mechanisms are working to scale up its availability. Stark highlights ongoing efforts to ensure equitable access, particularly for remote and Indigenous communities.
“New technologies like this have the potential to widen the gap between well-off and less-well-off populations, so we need to be mindful and take action to address these gaps,” she emphasises. “Our goal is to make genomic sequencing a first-line diagnostic tool, accessible to every patient who needs it.”
Towards equitable access to genomic testing
Australia’s genomic newborn screening programs have shown promise, and their implications stretch far beyond national borders. Countries like the US and the UK are scaling up newborn genomic screening initiatives, integrating sequencing into public health strategies to detect and treat rare diseases before symptoms appear.
However, ensuring equitable access to these advancements globally remains a major challenge. The implementation of genomic screening programs requires significant investment in infrastructure, bioinformatics expertise, and policy frameworks to support their integration into national healthcare systems.
While high-income countries are rapidly integrating genomic technologies, low- and middle-income countries (LMICs) face significant barriers. The high cost of sequencing, lack of specialised expertise, and limited laboratory infrastructure make it difficult for many LMICs to adopt whole-genome sequencing on a large scale.
ThankGod Ebenezer, a Nigerian bioinformatician, genomics advocate, and co-chair of the African BioGenome Project, is working to bridge this gap. His work focuses on building local infrastructure and ensuring that African researchers have the tools to conduct their own genomic studies.
This shift is not just about scientific independence; it ensures that local diseases and populations are studied with African-led solutions.
“In the past, sequencing was almost always outsourced to labs in Europe or North America,” Ebenezer says. “This meant that African scientists had little control over the process, and the data generated often didn’t serve local priorities.”
Several African institutions—including the Institute of Genomics and Global Health in Nigeria and the Centre for Epidemic Response and Innovation in South Africa—have begun sequencing genomes on the continent, reducing dependency on international facilities. This has been possible with the help of partnership initiatives brokered by the World Health Organization (WHO) and funding efforts led by a range of local, regional, and international organisations.
This shift is not just about scientific independence; it ensures that local diseases and populations are studied with African-led solutions. Furthermore, the ability to conduct sequencing locally fosters capacity building, training local researchers and creating a self-sustaining genomic ecosystem in Africa.
Advancing equity and international collaborations
The Africa Pathogen Genomics Initiative (Africa PGI 2.0), spearheaded by the Africa CDC, represents a significant step toward expanding genomic capabilities on the continent. Dr Yenew Kebede, acting director for laboratory network and systems at Africa CDC, says the initiative is a major milestone. “It will be a gamechanger for many disease outbreaks in Africa,” he explains.
Africa PGI 2.0 focuses on expanding genomic sequencing beyond infectious diseases, addressing conditions such as antimicrobial resistance, malaria, and inherited genetic disorders—including rare diseases. The initiative is increasing genomic capacity across more African countries and making advanced diagnostics more accessible. A major emphasis is also placed on workforce development, ensuring that African researchers and clinicians have the necessary training to sustain genomic programs.
“The ultimate goal is to integrate genomic sequencing into routine clinical practice, so that no patient, regardless of geography, is left behind,” Kebede says.
Global initiatives such as ClinGen and Genomics England also are working to ensure that genomic technologies benefit all populations, not just those in high-income countries. By sharing genomic data across borders, researchers can identify rare disease variants more efficiently and accelerate scientific discoveries.
Yet questions remain about data privacy and ethical considerations as there is a risk that sensitive patient data could end up in the wrong hands. “Sharing data has huge advantages for patients because we can use other people’s expertise, methods, and insights to help our patients. But it is still private patient information—how far can we go in sharing that?” Gilissen says, explaining that ethical guidelines are being developed by several large initiatives in the EU to protect patient privacy.
The future of genomic medicine in rare diseases
Beyond diagnosis, genomics is paving the way for precision medicine, where treatments are tailored to a person’s unique genetic makeup. Gene therapies—techniques that modify a person’s genes to treat or cure disease—were once a futuristic concept, but now they offer new hope for rare diseases that previously had no treatment options.
“The impact of these discoveries is profound—not just for diagnostics but for treatment strategies moving forward.”
Clinical trials are already underway for conditions such as spinal muscular atrophy and Duchenne muscular dystrophy, and have shown promising results in modifying or even correcting disease-causing mutations.
The challenge ahead is ensuring equitable access to these life-changing treatments. Without proper policies and funding models, precision medicine risks becoming a privilege rather than a global standard of care.
Stark emphasises the importance of sustainable healthcare funding. “Obtaining sustainable healthcare system funding, in the end, is what ensures much better access to the technology,” she says.
Clinical trials are already underway for conditions like spinal muscular atrophy. Photo: EasyStand
Despite the challenges that remain, there is growing optimism that genomic technology can make a real difference to the lives of people with rare diseases. Stark and her colleagues continue to push the boundaries, advocating for faster, more accessible genomic solutions. “For this technology to benefit as many people as possible, we really need to be scaling it up to the thousands and hundreds of thousands,” she explains.
Gilissen also sees progress on the horizon. “We are detecting variations in the genome that were invisible just a few years ago,” he explains. “The impact of these discoveries is profound—not just for diagnostics but for treatment strategies moving forward.”
For researchers like Ebenezer, the work in LMICs is just beginning, but the potential is undeniable. “We are building something sustainable here,” he says. “By training local scientists and strengthening genomic infrastructure, we are ensuring that African patients will benefit from these advancements.”
Gilissen says his team is working to ensure its breakthroughs benefit LMICs by prioritising education and training programs that equip local scientists with the knowledge to analyse and interpret genomic data independently.
“Building sequencing capacity is not just about having the technology—it’s about having the people who can use it effectively,” he says. “By sharing knowledge and fostering local expertise, we are empowering these communities to take control of their own rare disease diagnostics.”
No rare diseases go undiagnosed
These experts believe that the future of genomic medicine is still being written. Gilissen, whose work focuses on long-read sequencing and genome analysis to improve rare disease diagnosis, believes that the dream of a world where no rare disease goes undiagnosed is within reach.
Stark notes that it will take collaboration, investment, and a commitment to equity to ensure that this revolution benefits all—not just those in high-income countries. “We can’t afford to leave anyone behind,” she says. “Every patient deserves a diagnosis, and every life matters.”
It is clear the integration of whole-genome sequencing and genomic technologies into clinical practice is reshaping rare disease diagnosis and treatment. From Australia’s pioneering newborn screening programs to Africa’s expanding genomic capacity, progress is being made worldwide. Scaling these interventions equitably is the next frontier.
The question now is not whether genomics will transform rare disease care, but how quickly—and equitably—it can be done.
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