With the integration of whole genome sequencing in Swedish healthcare, some 1200 individuals with rare diseases have received a diagnosis, with novel disease genes discovered in the process.
“We’ve established a way of working where hospital and university collaborate on sequencing each patients’ entire genome in order to find genetic explanations for different diseases,” said first author Henrik Stranneheim, researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet. “This is an example of how precision medicine can be used to make diagnoses and tailor treatments to individual patients.”
The technology of large-scale whole genome sequencing to yield a person’s entire DNA, is not yet widely used in hospitals despite the technology becoming much more accessible over the last ten years. Whole genome sequencing has uncovered a great genetic variety among different populations, such as in South Africa, where a pilot study uncovered a high rate of novel variants in African populations.
Karolinska University Laboratory and the Clinical Genomics facility at SciLifeLab launched the Genomic Medicine Centre Karolinska-Rare Diseases (GMCK-RD) five years ago. Since then, the centre has sequenced the genomes of 3219 patients, which led to molecular diagnoses for 40% of them with rare diseases.
In addition to these, the researchers found pathogenic mutations in more than 750 genes and discovered 17 novel disease genes.
“Clinical whole genome sequencing has had huge implications for the area of rare diseases,” explained corresponding author Anna Wedell, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet. “Used in the right way, targeted at each patient’s specific clinical situation, new groups of patients can receive the right diagnosis and treatment in a way that hasn’t been possible before.”
Whole genome sequencing is challenging in part due to having to manage and interpret the millions of variations that exist within each invidual’s genome. In order to overcome this difficulty, the centre came up with a model that directs the initial analysis to pathogenic variants in genes relevant for that patient’s clinical symptomsIn this way, doctors play an important role in choosing which genetic analyses to run first.
Should the first assessment fail, the analyses are then broadened to more gene panels, which has uncovered new disease genes.
“For us to succeed with precision medicine, a multidisciplinary collaboration between health care and academia is essential,” said second corresponding author Anna Lindstrand, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet and consultant at Karolinska University Hospital’s Department of Clinical Genetics. “Through these initiatives we combine clinical expertise with bioinformatic tools and together deliver accurate diagnoses and individualised treatments.”
Source: Medical Xpress
Journal information: “Integration of whole genome sequencing into a health care setting: High diagnostic rates across multiple clinical entities in 3219 rare disease patients,” Genome Medicine (2021). DOI: 10.1186/s13073-021-00855-5
