Showing papers by "Douglas C. Wallace published in 1990"
TL;DR: An A to G transition mutation at nucleotide pair 8344 in human mitochondrial DNA has been identified as the cause of MERRF, providing molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production.
1,409 citations
TL;DR: The mitochondrial cytopathies are a heterogeneous group of diseases associated with defects in mitochondrial ATP production that affect the brain, skeletal muscle, heart, kidney, and liver.
Abstract: The mitochondrial cytopathies are a heterogeneous group of diseases associated with defects in mitochondrial ATP production that affect the brain, skeletal muscle, heart, kidney, and liver. Mitochondria produce ATP by oxidative phosphorylation (OXPHOS). OXPHOS involves approximately 100 polypeptides, most of which are encoded in the Mendelian-inherited nuclear genes, but 13 of which are encoded in the maternally-inherited mitochondrial DNA (mtDNA).
377 citations
Journal Article•
TL;DR: The analysis of mitochondrial DNA sequence variation of the South American Ticuna, the Central American Maya, and the North American Pima revealed that Amerindian populations have high frequencies of mtDNAs containing the rare Asian RFLP HincII morph 6, a rare HaeIII site gain, and a unique AluI site gain.
Abstract: The mitochondrial DNA (mtDNA) sequence variation of the South American Ticuna, the Central American Maya, and the North American Pima was analyzed by restriction-endonuclease digestion and oligonucleotide hybridization. The analysis revealed that Amerindian populations have high frequencies of mtDNAs containing the rare Asian RFLP HincII morph 6, a rare HaeIII site gain, and a unique AluI site gain. In addition, the Asian-specific deletion between the cytochrome c oxidase subunit II (COII) and tRNA(Lys) genes was also prevalent in both the Pima and the Maya. These data suggest that Amerindian mtDNAs derived from at least four primary maternal lineages, that new tribal-specific variants accumulated as these mtDNAs became distributed throughout the Americas, and that some genetic variation may have been lost when the progenitors of the Ticuna separated from the North and Central American populations.
362 citations
TL;DR: Variation in muscle OXPHOS analysis techniques may account for some of the discrepancies between clinical manifestations and OxPHOS defects and suggest that no single protocol is sufficient to adequately define the OX PHOS defect in MM patients.
140 citations
TL;DR: Examining three pairs of human diploid fibroblasts and their SV 40-transformed counterparts revealed that mRNAs for the nuclear-encoded ATP synthase beta and the adenine nucleotide translocator (ANT) isoform 1 and 2 genes were markedly induced, whereas the mRNA for the ANT isoform 3 gene remained unchanged.
123 citations
TL;DR: The developmental regulation of muscle bioenergetic metabolism appears to be regulated at the pretranslational level and is modulated by oxygen tension.
Abstract: Changes in the mRNA levels during mammalian myogenesis were compared for seven polypeptides of mitochondrial respiration (the mitochondrial DNA-encoded cytochrome oxidase subunit III, ATP synthase subunit 6, NADH dehydrogenase subunits 1 and 2, and 16S ribosomal RNA; the nuclear encoded ATP synthase beta subunit and the adenine nucleotide translocase) and three polypeptides of glycolysis (glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, and triose-phosphate isomerase). Progressive changes during the conversion from myoblasts to myotubes were monitored under both atmospheric oxygen (normoxic) and hypoxic environments. Northern analyses revealed coordinate, biphasic, and reciprocal expression of the respiratory and glycolytic mRNAs during myogenesis. In normoxic cells the mitochondrial respiratory enzymes were highest in myoblasts, declined 3- to 5-fold during commitment and exist from the cell cycle, and increased progressively as the myotubes matured. By contrast, the glycolytic enzyme mRNAs rose 3- to 6-fold on commitment and then progressively declined. When partially differentiated myotubes were switched to hypoxic conditions, the glycolytic enzyme mRNAs increased and the respiratory mRNAs declined. Hence, the developmental regulation of muscle bioenergetic metabolism appears to be regulated at the pretranslational level and is modulated by oxygen tension.
109 citations
TL;DR: It is demonstrated that in certain isolated instances, the proband and close maternal lineage relatives can have mixtures of mutant and normal mitochondrial DNA molecules (heteroplasmy), which means that the successful determination of the mitochondrial DNA genotype of a family or patient with Leber's hereditary optic neuropathy requires testing of more than one family member and more thanOne tissue from each individual.
107 citations
TL;DR: Three positive transcriptional control regions have been identified in the promoter of the human heart-skeletal muscle adenine nucleotide translocator gene (ANT1) and the OXBOX is the first tissue-specific element identified which could coordinately regulate mitochondrial oxidative phosphorylation genes.
73 citations
55 citations
TL;DR: Molecular analysis will likely become a primary tool for the diagnosis of neuromuscular diseases such as myoclonic epilepsy and ragged red fiber disease by identifying small deletions through amplification and electrophoretic analysis of the entire mtDNA genome.
Abstract: Mitochondrial DNA Mutations Associated with Neuromuscular Diseases: Analysis and Diagnosis Using the Polymerase Chain Reaction
22 citations
Patent•
14 Jun 1990TL;DR: In this paper, a method and manufacture for detecting neuromuscular disease, particularly myoclonic epilepsy and Ragged red fiber disease, by ascertaining whether a transition mutation has occurred at the 8344 nucleotide position in the mitochondrial DNA of a patient.
Abstract: The present invention relates to a method and manufacture for detecting neuromuscular disease, particularly Myoclonic Epilepsy and Ragged Red Fiber disease, by ascertaining whether a transition mutation has occurred at the 8344 nucleotide position in the mitochondrial DNA of a patient. The invention provides methods to detect this mutation including digestion of the patient's mtDNA with restriction endonucleases followed by analysis of the resulting fragments, differential hybridization of oligonucleotides, direct PCR sequencing and denaturing gradient gel electrophoresis.