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Comprehensive Analyses of the Mitochondrial Genome

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Next Generation Sequencing Based Clinical Molecular Diagnosis of Human Genetic Disorders

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Abstract

Comprehensive molecular diagnoses of mitochondrial DNA (mtDNA) related disorders must include detection and quantification of every single nucleotide variant (SNV) across the entire coding regions, as well as structural variations such as large deletions with mapping of the breakpoints. Traditionally, diagnosis of mtDNA-related disorders is achieved by employing step-wise procedures, such as PCR based Sanger sequencing for SNV, real time quantitative PCR for heteroplasmy quantification, and array CGH or Southern blot for large structural variations. Although these assays together have good clinical utility, these procedures are tedious and have technical limitations. More importantly, they may yield under-diagnoses or mis-diagnoses for some patients. The clinically validated massively parallel next generation sequencing (NGS) with deep coverage and proper quality control, as described “Zhang-Wong method”, can achieve a one-step cost-effective comprehensive diagnosis with greatly improved diagnostic yield, and is regarded as the “new gold standard” (Zhang et al. Clin. Chem. 58:1322–1331, 2012). The enhanced sensitivity, accuracy, and reproducibility of simultaneous detection and quantification of mtDNA SNVs, as well as the concurrent detection and junction characterization of single and multiple deletions offer extraordinary value in genetic counseling and patient management.

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Author information

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Victor Wei Zhang M.D., Ph.D. & Lee-Jun C. Wong Ph.D.

  2. AmCare Genomics Laboratory, International BioIsland 2-4C-201, GuangZhou, China

    Victor Wei Zhang M.D., Ph.D.

Authors
  1. Victor Wei Zhang M.D., Ph.D.
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  2. Lee-Jun C. Wong Ph.D.
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Correspondence to Victor Wei Zhang M.D., Ph.D. .

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Editors and Affiliations

  1. Molecular Diagnostic Laboratory, Baylor College of Medicine, Houston, Texas, USA

    Lee-Jun C. Wong

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Zhang, V.W., Wong, LJ.C. (2017). Comprehensive Analyses of the Mitochondrial Genome. In: Wong, LJ. (eds) Next Generation Sequencing Based Clinical Molecular Diagnosis of Human Genetic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-56418-0_13

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