Comprehensive analysis of mitochondrial genomes with NGS

New insights for mitochondrial disease research

Mitochondrial Sequencing

Mitochondrial disorders are heterogeneous, inherited diseases that can arise at any stage of life. Studying mutations associated with mitochondrial disorders remains a challenge due to phenotypic variability and genetic heterogeneity among individuals. Mitochondrial sequencing with next-generation sequencing (NGS) technology addresses some these challenges, enabling comprehensive detection and analysis of mitochondrial mutations.

Mitochondrial sequencing with NGS enables:

  • Detection of common and uncommon mitochondrial point mutations and deletions1,2,3,4
  • Rapid analysis of both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA)2,4
  • Accurate, sensitive measurement of heteroplasmy1 (more than one mitochondrial DNA sequence variant in a given sample)

Common NGS methods for analyzing mitochondrial disease-associated mutations include whole-exome sequencing and targeted gene sequencing.

Whole-exome sequencing analyzes the protein-coding regions of the genome, with the capability to expand to include untranslated regions (UTRs) and microRNAs if desired. Targeted gene sequencing focuses on specific genes or gene regions of interest with known or suspected disease associations. Compare the two methods in the table below.

Solutions for Mitochondrial Sequencing Studies
Method
Whole-Exome Sequencing
Targeted Gene Sequencing
Description

Provides a complete picture of the coding regions of the mitochondrial genome. Enables researchers to take a closer look at the mitochondrial regions where causative variants are often found.

Focuses on particular mitochondrial genes or gene regions. Utilizes gene panels that are selected based on a priori knowledge of mitochondrial disease-associated variants.

Advantages
  • Targets both mitochondrial and nuclear DNA in one assay
  • Detects novel variants
  • Accurately detects homopolymers and heteroplasmy with high depth of coverage
  • Cost-effectively queries defined mitochondrial or nuclear genes or gene regions based on suspected mutations
  • Detects heteroplasmy below 5% with increased coverage
  • Easy-to-interpret results simplify analysis
Considerations
  • More expensive than targeted methods
  • Results in larger data sets
  • May identify variants of unknown significance
  • Novel variants may be missed
  • Results in smaller data sets
  • Requires prior knowledge of genes of interest
Additional Information Learn more about whole-exome sequencing Learn more about targeted gene sequencing
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Analyzing Mitochondrial Mutations with NGS
Analyzing Mitochondrial Mutations with NGS

NGS enables analysis of the whole mitochondrial genome, providing researchers with a summary of molecular defects.

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NGS Offers New Insights for Mitochondrial Disease Research
NGS Offers New Insights for Mitochondrial Disease Research

Massively parallel sequencing provides a comprehensive, one-step molecular analysis of the mitochondrial genome.

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Identifying Heteroplasmy
Identifying Heteroplasmy

NGS enables researchers to quantify heteroplasmy accurately and detect mutations and deletions in mtDNA.

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References
  1. Tang S, Wang J, Zhang VW, et al. Transition to next generation analysis of the whole mitochondrial genome: a summary of molecular defects. Hum Mut. 2013;34:882-893.
  2. Wong LC. Next generation molecular diagnosis of mitochondrial disorders. Mitochondrion. 2013;13:379-387.
  3. Chinnery PF, Elliott HR, Hudson G, Samuels DC, Relton CL. Epigenetics, epidemiology and mitochondrial DNA diseases. Int J Epidemiol. 2012;41:177-187.
  4. Calvo SE, Compton AG, Hershman SG, et al. Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing. Sci Transl Med. 2012;4:118ra10.