More detailed studies have been made possible with whole genome sequences

More than 1,200 people with rare diseases have been diagnosed thanks to the introduction of large-scale genomics into the health care system of the Stockholm region. This is according to a study from Karolinska Institutet in Sweden which analyzed the outcome of the first five years of collaboration on a complete genome sequence between Karolinska University Hospital and SciLifeLab. The work, published in Genome Medicine, making up a major leap forward in the emerging field of precision medicine.

“We have established an approach where hospital and university work together to follow the whole genome of each patient to find a genetic explanation for different diseases,” says the paper’s first author Henrik Stranneheim , a researcher at the Karolinska Institute Department of Molecular Medicine and Surgery. “This is an example of how precision therapy can be used to diagnose and tailor treatments to individual patients.”

Large-scale genome attenuation technology, which is the process for determining a complete set of a person’s genetic material, has made rapid progress over the past decade. Nevertheless, very few clinics around the world use it routinely to diagnose patients.

Just over five years ago, the Karolinska University Laboratory and the Clinical Genomics facility at SciLifeLab launched the Karolinska-Rare Genomic Disease Medicine Center (GMCK-RD), which includes researchers from among another Karolinska Institutet and KTH Royal Institute of Technology.

In the first five years, the center performed a genome sequence of 3,219 patients, which led to molecular studies for 1,287 patients (40 percent) with rare diseases. The results are set out in the now published paper.

The researchers found pathogenic mutations in more than 750 genes and found 17 novel disease genes. In some cases, the findings have enabled personal treatment for patients with, for example, inherited metabolic diseases, rare epilepsies and primary immune deficiencies.

“Clinical whole genome sequences have had a profound impact on a range of rare diseases,” says Anna Wedell, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and one of the corresponding authors of the paper. “Used in the right way, focusing on the specific clinical situation of each patient, new groups of patients can receive the right diagnosis and treatment in a way that was not possible before.”

One of the key challenges to overall genome sequencing is the regulation and interpretation of the millions of genetic differences that exist in each individual. The center has therefore developed a model that leads the initial study to pathogenic changes in genes that are considered relevant for the clinical symptoms of all patients. This means that doctors play an important role in deciding which genetic analyzes should be performed first.

If the initial assessment does not yield results, the analysis will be extended to more gene panels until diagnosis is established and / or the whole genome is followed. This process has also enabled the identification of several previously unknown disease genes, which provides new opportunities for in-depth study of pathogenic mechanisms.

An important commitment is currently underway to implement a similar approach more widely in the Swedish healthcare sector. For example, Karolinska Institutet and Karolinska University Hospital recently established a joint center for precision medicine (PMCK) that reinforces the expansion of the collaboration around precision medicine.

“For the success of precision medicine, multidisciplinary collaboration between health care and academia is essential,” says the paper’s second co-author of the paper, Anna Lindstrand, professor at the Department of Molecular Medicine and Surgery. Karolinska Institute and consultant at Karolinska University Hospital Department of Clinical Genetics. “Through these initiatives we combine clinical experience with bioinformatic devices and together deliver accurate studies and individual treatments.”

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The study was funded by the Stockholm Region, the Swedish Research Council, the Swedish Brain Fund, the Karolinska Institutet, the Knut & Alice Wallenberg Foundation and the Research Council of Norway.

Disclosure: “Integration of whole genome sequences into a healthcare setting: High diagnostic rates across several clinical groups in 3219 patients with rare disease,” Henrik Stranneheim, Kristina Lagerstedt-Robinson, Måns Magnusson, Malin Kvarnung, Daniel Nilsson, Nicole Lesko, Martin Engvall, Britt-Marie Anderlid, Henrik Arnell, Carolina Backman Johansson, Michela Barbaro, Erik Björck, Helene Bruhn, Jesper Eisfeldt, Cristoph Freyer, Giedre Grigelioniene, Peter Gustavsson, Anna Hammarsjö, Maritta Hellström And Pigg Jemten, Sara Lind Enoksson, Helena Malmgren, Karin Naess, Magnus Nordenskjöld, Mikael Oscarson, Maria Pettersson, Chiara Rasi, Adam Rosenbaum, Ellika Sahlin, Eliane Sardh, Tommy Stödberg, Bianca Tesi, Emma Tham, Håkan Thonberg, Virpi. , Daphne Vassiliou, Sofie Vonlanthen, Ann-Charlotte Wikström, Josephine Wincent, Ola Winqvist, Anna Wredenberg, Sofia Ygberg, Rolf H Zetterström, Per Marits, Maria Johansson Soller, Ann Nordgren, Valtteri Wirta, Anna Lindstrand, Anna Wedell, Genome Medicine, online March 17, 2021, doi: 10.1186 / s13073-021-00855-5