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Genet Med. 2018 Nov 5. doi: 10.1038/s41436-018-0350-8. [Epub ahead of print]

eKLIPse: a sensitive tool for the detection and quantification of mitochondrial DNA deletions from next-generation sequencing data.

Author information

1
MitoLab, UMR CNRS 6015-INSERM U1083, MitoVasc Institute, Angers University, Angers, France.
2
Biochemistry and Genetics Department, Angers Hospital, Angers, France.
3
Biochemistry Department and Genetics Center, APHP, GHU Pitié-Salpêtrière, Paris, France.
4
Université Côte d'Azur, CHU de Nice, INSERM, CNRS, IRCAN, Nice, France.
5
CHU Reims, Hôpital Maison Blanche, Pole de biologie, Service de génétique, Reims, France.
6
MitoLab, UMR CNRS 6015-INSERM U1083, MitoVasc Institute, Angers University, Angers, France. ViProcaccio@chu-angers.fr.
7
Biochemistry and Genetics Department, Angers Hospital, Angers, France. ViProcaccio@chu-angers.fr.

Abstract

PURPOSE:

Accurate detection of mitochondrial DNA (mtDNA) alterations is essential for the diagnosis of mitochondrial diseases. The development of high-throughput sequencing technologies has enhanced the detection sensitivity of mtDNA pathogenic variants, but the detection of mtDNA rearrangements, especially multiple deletions, is still poorly processed. Here, we present eKLIPse, a sensitive and specific tool allowing the detection and quantification of large mtDNA rearrangements from single and paired-end sequencing data.

METHODS:

The methodology was first validated using a set of simulated data to assess the detection sensitivity and specificity, and second with a series of sequencing data from mitochondrial disease patients carrying either single or multiple deletions, related to pathogenic variants in nuclear genes involved in mtDNA maintenance.

RESULTS:

eKLIPse provides the precise breakpoint positions and the cumulated percentage of mtDNA rearrangements at a given gene location with a detection sensitivity lower than 0.5% mutant. eKLIPse software is available either as a script to be integrated in a bioinformatics pipeline, or as user-friendly graphical interface to visualize the results through a Circos representation ( https://github.com/dooguypapua/eKLIPse ).

CONCLUSION:

Thus, eKLIPse represents a useful resource to study the causes and consequences of mtDNA rearrangements, for further genotype/phenotype correlations in mitochondrial disorders.

KEYWORDS:

mitochondrial diseases; mitochondrial genome; mtDNA deletions; next-generation sequencing; soft clipping

PMID:
30393377
DOI:
10.1038/s41436-018-0350-8

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