Abstract
Human mitochondrial DNA (mtDNA) is a closed circular genome of 16,569 bp (1), encoding 13 subunits of four enzyme complexes (Complexes I, III, IV, and V) in the oxidative phosphorylation system (2). Mutations of mtDNA have been demonstrated to be associated with various neuromuscular diseases. Point mutations of mtDNA are reported in MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) (3,4), MERRF syndrome (myoclonus epilepsy associated with ragged-red fibers) (5,6), Leber’s disease (hereditary optic neuropathy) (7), a type of encephalomyopathy (8), and fatal infantile cardiomyopathy (9). Deletions of mtDNA are observed in Kearns-Sayre syndrome and chronic progres sive external ophthalmoplegia (CPEO) (10). It is also proposed that accumulation of mtDNA mutations is an important contributor to several degenerative diseases and the aging process (11). Evidence supporting this hypothesis has been presented in Parkinson’s disease (12,13), cardiomyopathy (14,15), and presbycardia (16). Therefore, the analysis of mtDNA mutations seem to be increasing their importance both in clinical neurology and in the basic neurological science.
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References
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., and Young, I. G. (1981) Sequence and organization of the human mitochondrial genome. Nature 290, 457–465.
Chomyn, A., Mariottini, P., Cleeter, M. W. J., Ragan, C. I., Doolittle, R. F., Matsuno-Yagi, A., Hatefi, Y., and Attardi, G. (1985) Functional assignment of the products of the unidentified reading frames of human mitochondrial DNA, in Achievements and Perspectives of Mitohndrial Research. vol. II: Biogenesis (Quagliariello, E., Slater, E. C., Palmieri, F., Saccone, C., and Kroon, A. M., eds.), Elsevier, Amsterdam, NY, pp. 259–275.
Tanaka, M., Ino, H., Ohno, K., Ohbayashi, T., Ikebe, S., Sane, T., Ichiki, T., Kobayashi, M., Wada, Y., and Ozawa, T. (1991) Mitochondrial DNA mutalike in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), Biochem. Biophys. Res. Commun. 174, 861–868.
Ino, H., Tanaka, M., Ohno, K, Hattori, K, Ikebe, S., Ozawa, T., Sano, T., Ichiki, T., Kobayashi, M., and Wada, Y. (1991) Mitochondrial leucine tRNA mutation in mitochondrial encephalomyopathy. Lancet 337, 234–235.
Yoneda, M., Tanno, S., Horai, S., Ozawa, T., Miyatake, T., and Tsuji, S. (1990) A common mitochondrial DNA mutation in the t-RNALys of patients with myoclonus epilepsy associated with ragged-red fibers. Biochem. Int. 27, 789–796.
Shoffner, J. M., Lott, M. T., Lezza, A. M. S., Seibel, P., Ballinger, S. W., and Wallace, D. C. (1990) Myclonic epilepsy and ragged-red fibers disease (MERRF) is associated with a mitochondrial DNA t-RNALys mutation. Cell 61, 931–937.
Wallace, D. C., Singh, G., Lott, M. T., Hodge, J. A., Schurr, T. G., Lezza, A. M.S., Eisas, L.J., and Nikoskelainen, E. K. (1983) Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science 242, 1427–1430.
Holt, I.J., Harding, A. E., Petty, R. K., and Morgan-Hughes, J. A. (1990). A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am. J. Hum. Genet. 46, 428–433.
Tanaka, M., Ino, H., Ohno, K., Hattori, K., Sato, W., and Ozawa, T. (1990) Mitochondrial tRNAIle mutation in fatal infantile cardiomyopathy. Lancet 336, 14
Ozawa, T., Yoneda, M., Tanaka, M., Ohno, K., Sate, W., Suzuki, H., Nishikimi, M., Yamamoto, M., Nonaka, I., and Horai, S. (1988) Maternal inheritance of deleted mitochondrial DNA in a family with mitochondrial myopathy. Biochem. Biophys. Res. Commun. 154, 1240–1247.
Linnane, A. W., Marzuki, S., Ozawa, T., and Tanaka, M. (1989) Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet i, 642–645.
Ikebe, S., Tanaka, M., Ohno, K., Sate, W., Hattori, K., Kondo, T., Mizuno, Y., and Ozawa, T. (1990) Increase of deleted mitochondrial DNA in the striatum in Parkinson’s disease and senescence. Biochem. Biophys. Res. Commun. 170, 1044–1048.
Ozawa, T., Tanaka, M., Ikebe, S., Ohno, K., Kondo, T., and Mizuno, Y. (1990) Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis. Biochem. Biophys. Res. Commun. 172, 483–489.
Ozawa, T., Tanaka, M., Sugiyama, S., Hattori, K, Ito, T., Ohno, K., Takahashi, A., Sato, W., Takada, G., Mayumi, B., Yamamoto, K., Adachi, K., Koga, Y., and Toshima, H. (1990). Multiple mitochondrial DNA deletions exist in cardiomyocytes of patients with hypertrophic or dilated cardiomyopathy. Biochem. Biophys. Res. Commun. 154, 830–836.
Hattori, K., Ogawa, T., Taizo, K., Mochizuki, M., Tanaka, M., Sugiyama, S., Ito, T., Satake, T., and Ozawa, T. (1991) Cardiomyopathy with mitochondrial DNA mutations. Am. Heart J. 122, 866–869.
Hattori, K., Tanaka, M., Sugiyama, S., Obayashi, T., Ito, T., Satake, T., Hanaki, Y., Asai, J., Nagano, M., and Ozawa, T. (1991) Age-dependent increase in deleted mitochondrial DNA in the human heart: Possible contributing factor to “presbycardia.”0. Am. Heart J. 121, 1735–1745.
Higuchi, R., Beroldingen, C. H. V., Sensabaugh, G. F., and Erlich, H. A. (1988) DNA typing from single hairs. Nature 332, 543–546.
Innis, M. A., Myambo, K. B., Gelfand, D. H., and Brow, M. A. (1988) DNA sequencing with Thermus aquatics DNA polymerase and direct sequencing of polymerase chain reaction-amplified DNA. Proc. Natl. Acad. Sai. USA 85, 9436–9440.
Tanaka, M., Sato, W., Ohno, K, Yamamoto, T., and Ozawa, T. (1989) Direct sequencing of deleted mitochondrial DNA in myopathic patients. Biochem. Biophys. Res. Commun. 164, 156–163.
Gyllensten, U. B. and Erlich, H. A. (1988) Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc. Natl. Acad. Sci. USA 85, 7652–7656.
Ohno, K., Tanaka, M., Sahashi, K., Ibi, T., Sato, W., Takahashi, A., and Ozawa, T. (1991) Mitochondrial DNA deletions in inherited recurrent myoglobinuria. Ann. Neurol. 29, 364–369.
Sate, W., Tanaka, M., Ohno, K., Yamamoto, T., Takada, G., and Ozawa, T. (1989) Multiple populations of deleted mitochondrial DNA detected by a novel gene amplification method. Biochem. Biophys. Res. Commun. 162, 664–672. 23.
Tanaka-Yamamoto, T., Tanaka, M., Ohno, K., Sate, W., Horai, S., and Ozawa, T. (1989) Specific amplification of deleted mitochondrial DNA from a myopathic patient and analysis of deleted region with S1 nuclease. Biochim. Biophys Acta 1009, 151–155.
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© 1992 The Humana Press, Totowa, NJ
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Tanaka, M., Ozawa, T. (1992). Analysis of Mitochondrial DNA Mutations. In: Longstaff, A., Revest, P. (eds) Protocols in Molecular Neurobiology. Methods in Molecular Biology™, vol 13. Springer, Totowa, NJ. https://doi.org/10.1385/0-89603-199-3:25
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DOI: https://doi.org/10.1385/0-89603-199-3:25
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