Our understanding of the genetic mechanisms underlying rare diseases has rapidly advanced over the past decade, largely because of technological innovations. Yet clinical practice still has a strong monogenic focus, leaving many individuals undiagnosed. This Comment outlines how technological advances such as long-read sequencing should be adopted to increase multivariant testing in the clinic.
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Acknowledgements
A.K. was funded by the Swedish Society for Medical Research (PD20-0190) and Erik Philip-Sörensens stiftelse. A.L. was funded by grants from the Swedish Research Council (2019-02078), Region Stockholm (FoUI-1000468 and FoUI-978581), the Rare Diseases Research Foundation (Sällsyntafonden), the Swedish Brain Foundation (FO2024-0128-HK-44) and the Swedish Cancer Society (24 3504 Pj). We are also thankful to M. Ek for help with figure design.
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A.L., J.E. and A.K. conceived of the article, A.K and J.E. designed the figures, A.K. and O.B.P wrote the manuscript and all authors were involved in revisions.
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AL has received speakers’ honoraria from Pacific Biosciences and Illumina.
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Kämpe, A., Blomqvist Picard, O., Eisfeldt, J. et al. Moving beyond monogenic disorders in clinical healthcare. Nat Biotechnol 44, 21–25 (2026). https://doi.org/10.1038/s41587-025-02931-2
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DOI: https://doi.org/10.1038/s41587-025-02931-2
