mitochondrial disorders biochemical and molecular analysis

[...]... rate, and these mutations can exhibit a complex and broad spectrum of disease manifestations The properties of maternal inheritance, heteroplasmy, tissue- and 1 Mitochondrial DNA Mutations: An Overview of Clinical and Molecular Aspects 13 cell-specific threshold effects, and mitotic segregation all interact to make for a unique set of clinical challenges in the diagnosis and management of mitochondrial disorders. .. Lee-Jun C Wong (ed.), Mitochondrial Disorders: Biochemical and Molecular Analysis, Methods in Molecular Biology, vol 837, DOI 10.1007/978-1-61779-504-6_2, © Springer Science+Business Media, LLC 2012 17 18 F Scaglia syndromes that are characterized by secondary abnormalities of mtDNA Thus, mitochondrial disorders of oxidative phosphorylation can be classified into two categories: disorders caused by mutations... Krishnan, K J., and Turnbull, D (2008) Mitochondrial DNA mutations in disease, aging, and neurodegeneration, Ann N Y Acad Sci 1147, 21–29 9 Smits, P., Smeitink, J., and van den Heuvel, L (2010) Mitochondrial translation and beyond: processes implicated in combined oxidative phosphorylation deficiencies, J Biomed Biotechnol 2010, 737385 10 Zeviani, M., and Di Donato, S (2004) Mitochondrial disorders, Brain... poorly understood interactions between the mutation and the genetic “background” (22) and may predispose individuals to more common disorders (23) 1 Mitochondrial DNA Mutations: An Overview of Clinical and Molecular Aspects 7 4 mtDNA Mutations Given the wide clinical variability and a lack of simple, definitive testing, the prevalence of mitochondrial disorders is difficult to accurately measure (24) However,... nucleotide modification and alternative folding of RNA, Nucleic Acids Res 34, 721–733 1 Mitochondrial DNA Mutations: An Overview of Clinical and Molecular Aspects 48 Florentz, C., Sohm, B., Tryoen-Toth, P., et al (2003) Human mitochondrial tRNAs in health and disease, Cell Mol Life Sci 60, 1356–1375 49 Finsterer, J (2007) Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G... aminoacylation of the tRNA and a lack of wobble-base hypermodification This posttranscriptional taurine modification at the anticodon wobble position is needed to restrict decoding to leucineUUR codons, and loss of this 1 Mitochondrial DNA Mutations: An Overview of Clinical and Molecular Aspects 11 modification leads to a combination of a decoding defect of UUG and UUA codons and amino acid misincorporation... of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA ZHE ZHANG • Center for Biomedical Informatics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA xi Part I Mitochondrial Disorder: A Complex Disease of the Two Genomes sdfsdf Chapter 1 Mitochondrial DNA Mutations: An Overview of Clinical and Molecular Aspects William J Craigen Abstract Mutations that arise in mitochondrial. .. (OXPHOS) pathway, modulating apoptosis or programmed cell death, providing a means to buffer and regulate calcium homeostasis, and participating Lee-Jun C Wong (ed.), Mitochondrial Disorders: Biochemical and Molecular Analysis, Methods in Molecular Biology, vol 837, DOI 10.1007/978-1-61779-504-6_1, © Springer Science+Business Media, LLC 2012 3 4 W.J Craigen in cell cycle regulation through “retrograde... Isolation of Possible Mitochondrial Precursor Structures from Aerobically Grown Baker’s Yeast, Biochem Biophys Res Commun 12, 448–451 12 Nass,M.M.,andNass,S.(1963)Intramitochondrial Fibers with DNA Characteristics I Fixation and Electron Staining Reactions, J Cell Biol 19, 593–611 13 Holt, I J., Harding, A E., and MorganHughes, J A (1988) Deletions of muscle mitochondrial DNA in patients with mitochondrial. .. Lorimer, H E., and Jacobs, H T (2000) Coupled leading- and lagging-strand synthesis of mammalian mitochondrial DNA, Cell 100, 515–524 Krishnan, K J., Reeve, A K., Samuels, D C., et al (2008) What causes mitochondrial DNA deletions in human cells?, Nat Genet 40, 275–279 Sadikovic, B., Wang, J., El-Hattab, A., et al (2010) Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA . http://www.springer.com/series/7651 Mitochondrial Disorders Biochemical and Molecular Analysis Edited by Lee-Jun C. Wong Mitochondrial Diagnostic Laboratory, Department of Molecular and Human Genetics, Baylor. Part I Mitochondrial Disorder: A Complex Disease of the Two Genomes sdfsdf 3 Lee-Jun C. Wong (ed.), Mitochondrial Disorders: Biochemical and Molecular Analysis, Methods in Molecular Biology,. Chapman, and Marni J. Falk 17 Molecular Profiling of Mitochondrial Dysfunction in Caenorhabditis elegans . . . . . . 241 Erzsebet Polyak, Zhe Zhang, and Marni J. Falk PART III MOLECULAR ANALYSIS OF MITOCHONDRIAL