期刊
GENETICS IN MEDICINE
卷 21, 期 6, 页码 1407-1416出版社
SPRINGERNATURE
DOI: 10.1038/s41436-018-0350-8
关键词
mitochondrial diseases; mitochondrial genome; mtDNA deletions; next-generation sequencing; soft clipping
资金
- Association contre les Maladies Mitochondriales
- University and Hospital of Angers
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.
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