University of Oulu

Mantere, T., Kersten, S., & Hoischen, A. (2019). Long-Read Sequencing Emerging in Medical Genetics. Frontiers in Genetics, 10.

Long-read sequencing emerging in medical genetics

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Author: Mantere, Tuomo1,2; Kersten, Simone1,3,4; Hoischen, Alexander1,3,4
Organizations: 1Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
2Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit and Biocenter Oulu, University of Oulu, Oulu, Finland
3Department of Internal Medicine, Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, Netherlands
4Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.9 MB)
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Language: English
Published: Frontiers Media, 2019
Publish Date: 2019-09-26


The wide implementation of next-generation sequencing (NGS) technologies has revolutionized the field of medical genetics. However, the short read lengths of currently used sequencing approaches pose a limitation for the identification of structural variants, sequencing repetitive regions, phasing of alleles and distinguishing highly homologous genomic regions. These limitations may significantly contribute to the diagnostic gap in patients with genetic disorders who have undergone standard NGS, like whole exome or even genome sequencing. Now, the emerging long-read sequencing (LRS) technologies may offer improvements in the characterization of genetic variation and regions that are difficult to assess with the prevailing NGS approaches. LRS has so far mainly been used to investigate genetic disorders with previously known or strongly suspected disease loci. While these targeted approaches already show the potential of LRS, it remains to be seen whether LRS technologies can soon enable true whole genome sequencing routinely. Ultimately, this could allow the de novo assembly of individual whole genomes used as a generic test for genetic disorders. In this article, we summarize the current LRS-based research on human genetic disorders and discuss the potential of these technologies to facilitate the next major advancements in medical genetics.

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Series: Frontiers in genetics
ISSN: 1664-8021
ISSN-E: 1664-8021
ISSN-L: 1664-8021
Volume: 10
Article number: 426
DOI: 10.3389/fgene.2019.00426
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3111 Biomedicine
Funding: AH was supported by the Solve-RD project. The Solve-RD project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 779257. TM was supported by the Sigrid Jusélius Foundation. The Radboud Institute for Molecular Life Sciences supported AH and SK.
Copyright information: © 2019 Mantere, Kersten and Hoischen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.