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Biochemical and Molecular Methods for the Study of Mitochondrial Disorders

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Mitochondrial Disorders Caused by Nuclear Genes

Abstract

Mitochondrial respiratory chain disorders (RCD) are a group of genetically and clinically heterogeneous diseases that can be caused by mutations in the mitochondrial or nuclear genome. Due to the complexity of the disorders and the consideration of the two genomes, diagnosis of these disorders can be difficult. Diagnosis requires the combination of clinical, biochemical, histopathological, imaging, and molecular evaluations. Usually, the disease is first suspected based on clinical assessment, followed by simple analyses of metabolic markers. The diagnosis of the disease maybe supported by non-invasive imaging evaluation, for example, magnetic resonance imaging (MRI) or magnetic resonance spectrum (MRS), or biochemical and histochemical studies of invasive muscle biopsies. The definitive diagnosis is usually arrived by the identification of the causative deleterious mutations in the genes involved in mitochondrial biogenesis, respiratory chain function, or other mitochondrial structural/functional proteins. Based on years of clinical and diagnostic experience, a molecular testing algorithm has been developed. Various biochemical and molecular methods used in the diagnostic algorithms are described in this chapter. The application of novel technologies including oligonucleotide array comparative genome hybridization (aCGH), and massively parallel sequencing of target genes are reviewed. Capture of all genes targeting to the mitochondria followed by new generation high throughput sequencing may be the ultimate approach for a one-step comprehensive molecular diagnosis of complex dual genome mitochondrial disorders.

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  1. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, 77030, Houston, TX, USA

    Lee-Jun C. Wong PhD

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  1. Lee-Jun C. Wong PhD
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Correspondence to Lee-Jun C. Wong PhD .

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  1. , Dept. of Molecular and Human Genetics, Baylor College of Medicine, Baylor Plaza ONE, Houston, 77030, Texas, USA

    Lee-Jun C. Wong

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Wong, LJ.C. (2013). Biochemical and Molecular Methods for the Study of Mitochondrial Disorders. In: Wong, LJ. (eds) Mitochondrial Disorders Caused by Nuclear Genes. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3722-2_2

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