Whole-genome sequencing in routine care is now solving rare disease cases at scale, with programs like Karolinska’s finding definitive genetic answers in nearly one in four patients and turning years of uncertainty into actionable diagnoses.
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In Destiny’s Child No Longer: Rewriting Genetic Fate, we argued that the time has come to use complete DNA sequencing, in utero where possible and for every newborn, to identify, prevent or lessen the impact of serious inherited diseases over a lifetime. A new study from the Karolinska Institute reinforces that this approach is practical, effective in real-world clinical settings and capable of substantially reducing the lifetime consequences of inherited disease.
The Genomic Medicine Center at the Karolinska Institute in Stockholm analyzed the DNA of more than 15,000 people with suspected genetic conditions and identified a clear genetic cause in nearly one in every four. The study represents one of the largest clinical genome sequencing efforts reported to date.
Every person carries a unique set of small variations in DNA. Most are harmless. Some disrupt the function of critical genes and cause disease. A rare disease is a health condition that affects a small percentage of the population. More than 7,000 such conditions exist, many with overlapping symptoms that make them difficult to identify through standard medical testing. Families visit dozens of medical experts over many years before receiving a diagnosis. For many, that journey ends without an answer.
The program reads the complete set of genetic instructions, the genome, of each person referred for evaluation. It covers multiple disease categories, from intellectual disabilities, epilepsy, and immune disorders to inherited cancers, metabolic conditions, skeletal abnormalities, heart conditions and neurodegenerative diseases. Computer tools sift through millions of variations in each genome. They flag the ones most likely to cause harm and present them to a multidisciplinary team for review.
Between 2015 and 2023, the program analyzed over 15,000 people, split almost evenly between children and adults. Of those, 22.6% received a confirmed genetic diagnosis. The program identified harmful changes across 1,570 genes and reported more than 4,400 disease-causing variants.
More than half of all diagnoses involved genes found in only one to three people across the entire program. This underscores how individually rare many of these conditions are and why standard tests miss them. Reading the complete genome casts a wider net than targeted tests, which examine only a small fraction of a person’s genetic code.
A genetic diagnosis changes lives because it enables action. Once the cause of a disease is known, a family can act to monitor, prevent or treat it, rather than wait for symptoms to appear.
For a child with a newly identified metabolic disorder, a genetic diagnosis can mean starting a targeted diet or medication that prevents irreversible brain damage. For someone with epilepsy, it can mean switching to the right seizure medication after years on the wrong one. For a family carrying an inherited cancer risk, it can prompt earlier screening that catches tumors at a treatable stage. For families with an unborn child showing signs of a skeletal abnormality, it can guide critical decisions before birth.
Early diagnosis makes treatment, management or even prevention possible for many conditions. Combined with emerging therapies that correct disease pathways at the genetic level, genetic diagnosis becomes the first step toward changing the course of inherited disease. Even when no specific treatment exists, a diagnosis brings clarity, connects families with support networks, opens access to clinical trials and ends years of uncertainty.
This approach is no longer theoretical. A statewide effort under Florida’s Sunshine Genetics Act sequences the genomes of up to 100,000 newborns, screening for more than 750 treatable genetic conditions. The program detects inherited diseases before symptoms appear and begins treatment immediately.
Health systems worldwide move in the same direction. The United Kingdom’s National Health Service commits £650 million to sequence the genome of every newborn in England. Programs in Australia, Singapore and across Scandinavia expand similar efforts. A recent world record set the time to read one complete human genome at under four hours.
The Karolinska model offers these programs a practical and proven blueprint. Its analysis software is available online as open-source code. It enables other centers to adopt the same methods. The team-based approach, pairing genetic data with deep clinical expertise across multiple medical fields, also shows how to turn raw DNA readings into meaningful answers for real people.
As envisioned in Destiny’s Child No Longer, the era of universal genetic screening draws closer. A decade of evidence shows that comprehensive DNA sequencing at the start of life can identify inherited disease, guide early treatment and reduce the burden of genetic illness for generations to come.
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