caa a22 4500 397575769 CHVBK 20180308164855.0 cr unu---uuuuu 161202e199604 xx s 000 0 eng 10.1093/hmg/5.4.473 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.4.473 Do Sequence Variants in the Major Non-Coding Region of the Mitochondrial Genome Influence Mitochondrial Mutations Associated with Disease? [Elektronische Daten] [David R. Marchington, Joanna Poulton, Anneke Sellar, Ian J. Holt] Several different mutations in human mitochondrial DNA (mtDNA) have been associated with disease, but their origins and the basis of the wide phenotypic variability remain to be elucidated. We initially investigated three patients with heteroplasmic disease associated mutations of mtDNA for the presence of cis mutations in the major non-coding region that might influence their origins or pathology. A T→C transition at nt 16 189 previously identified in one patient with the 3243 G:C mutation was associated with heteroplasmic length variation. Identical length variation was found in patient-derived cybrid lines containing 0-97.5% 3243 G:C. Similarly, heteroplasmic length variation was demonstrated in 2/6 other probands with both the 3243 mutation and the 16 189 polymorphism. The distribution of length variants in probands and in asymptomatic family members was identical in all cases. Thus length variation appears to be independent of the level of 3243 mutant mtDNA and hence probably arose within both 3243 G:C and 3243 A:T mtDNAs. We suggest that the 16 189 polymorphism reflects a predisposition to the formation or fixation of several different mutations in mitochondrial tRNA-leuUUR. © 1996 Oxford University Press Marchington David R. Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK aut Poulton Joanna Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK aut Sellar Anneke Oxford Medical Genetics Laboratory, Churchill Hospital, Oxford OX3 7LJ, UK aut Holt Ian J. Department of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK aut Human Molecular Genetics Oxford University Press 5/4(1996-04), 473-479 0964-6906 5:4<473 1996 5 hmg https://doi.org/10.1093/hmg/5.4.473 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.4.473 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Marchington David R. Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK aut NATIONALLICENCE 700 1- Poulton Joanna Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK aut NATIONALLICENCE 700 1- Sellar Anneke Oxford Medical Genetics Laboratory, Churchill Hospital, Oxford OX3 7LJ, UK aut NATIONALLICENCE 700 1- Holt Ian J. Department of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/4(1996-04), 473-479 0964-6906 5:4<473 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford