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Mitochondrial and nuclear disease panel (Mito-aND-Panel): Combined sequencing of mitochondrial and nuclear DNA by a cost-effective and sensitive NGS-based method

Lookup NU author(s): Professor Rita HorvathORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2018 Medical Genetics Center Munich. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. Background: The diagnosis of mitochondrial disorders is challenging because of the clinical variability and genetic heterogeneity of these conditions. Next-Generation Sequencing (NGS) technology offers a robust high-throughput platform for nuclear and mitochondrial DNA (mtDNA) analyses. Method: We developed a custom Agilent SureSelect Mitochondrial and Nuclear Disease Panel (Mito-aND-Panel) capture kit that allows parallel enrichment for subsequent NGS-based sequence analysis of nuclear mitochondrial disease-related genes and the complete mtDNA genome. Sequencing of enriched mtDNA simultaneously with nuclear genes was compared with the separated sequencing of the mitochondrial genome and whole exome sequencing (WES). Results: The Mito-aND-Panel permits accurate detection of low-level mtDNA heteroplasmy due to a very high sequencing depth compared to standard diagnostic procedures using Sanger sequencing/SNaPshot and WES which is crucial to identify maternally inherited mitochondrial disorders. Conclusion: We established a NGS-based method with combined sequencing of the complete mtDNA and nuclear genes which enables a more sensitive heteroplasmy detection of mtDNA mutations compared to traditional methods. Because the method promotes the analysis of mtDNA variants in large cohorts, it is cost-effective and simple to setup, we anticipate this is a highly relevant method for sequence-based genetic diagnosis in clinical diagnostic applications.

Publication metadata

Author(s): Abicht A, Scharf F, Kleinle S, Schon U, Holinski-Feder E, Horvath R, Benet-Pages A, Diebold I

Publication type: Article

Publication status: Published

Journal: Molecular Genetics and Genomic Medicine

Year: 2018

Volume: 6

Issue: 6

Pages: 1118-1198

Print publication date: 01/11/2018

Online publication date: 08/11/2018

Acceptance date: 10/10/2018

Date deposited: 19/11/2018

ISSN (electronic): 2324-9269

Publisher: John Wiley & Sons Ltd

URL: https://doi.org/10.1002/mgg3.500

DOI: 10.1002/mgg3.500

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