- Dr Stefen Brady, Clinical Research Fellow
- Mr Alan Diot, Visiting Research Assistant
- Miss Lorna MacLeod, D Phil student
- Dr Chunyan Liao, Postdoctoral Research Assistant
Former Group Members
- Dr Neil Ashley, Postdoctoral Research Assistant
- Mr Marcos Chiaratti, Visiting D Phil Student
- Dr Magda Plotka, Postdoctoral Research Assistant
- Dr Elizabeth Rapa, Postdoctoral Research Assistant
- Dr Johanna Uusimma, Visiting Clinical Research Fellow
- Dr Karl Morten, Senior Research Scientist
- Fratter CA, Raman P, Alston CL, Blakely EL, Craig K, Smith C, Evans JC, Seller A, Czermin B, Hanna M, Poulton J, Brierley C, Stauton T, Turnpenny P, Schaefer A, Chinnery P, Horvath R, Turnbull D, Gorman G, and Taylor R (2011) RRM2B mutations are frequent in familial PEO with multiple mtDNA deletions Neurology, Jun 7;76(23):2032-4.
- Uusimaa J, Jungbluth H, Fratter C, Crisponi G, Feng L, Zeviani M, Hughes I, Treacy E P, Birks J, Brown G K, Sewry C A, McDermott M, Muntoni F, and Poulton J (2011) Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease. J Med Genet, 48(10):660-8.
- Fratter C, Gorman G S, Stewart J D, Buddles M, Smith C, Evans J, Seller A, Poulton J, Roberts M, Hanna M G, Rahman S, Omer S E, Klopstock T, Schoser B, Kornblum C, Czermin B, Lecky B, Blakely E L, Craig K, Chinnery P F, Turnbull D M, Horvath R, and Taylor R W (2010) The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO. Neurology, 74(20):1619-26.
- Haack Tobias B, Danhauser Katharina, Haberberger Birgit, Hoser Jonathan, Strecker Valentina, Boehm Detlef, Uziel Graziella, Lamantea Eleonora, Invernizzi Federica, Poulton Joanna, Rolinski Boris, Iuso Arcangela, Biskup Saskia, Schmidt Thorsten, Mewes Hans-Werner, Wittig Ilka, Meitinger Thomas, Zeviani Massimo, and Prokisch Holger (2010) Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Nat Genet, 42(12):1131-4.
- Marchington D, Malik S, Banerjee A, Turner K, Samuels David, Macaulay V, Oakeshott P, Fratter C, Kennedy S, and Poulton J (2010) Information for genetic management of mtDNA disease: sampling pathogenic mtDNA mutants in the human germline and in placenta. J Med Genet, 47(4):257-61.
|Contact address||NDOG, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, Oxfordshire, OX3 9DU, United Kingdom|
|Department||Nuffield Department of Obstetrics and Gynaecology|
|College||Lady Margaret Hall|
Research Interests include:
- Transmission and recurrence risks in mtDNA disease: The unique way in which mitochondrial DNA (mtDNA) is transmitted makes genetic counselling difficult. Dramatic changes in level of mutant mtDNA are attributable to a "genetic bottleneck" whereby a small number of mtDNAs become the founders for the offspring. We are studying the basis of this bottleneck in families and embryos, and are developing novel approaches to genetic counselling of mtDNA diseases, namely oocyte sampling and pre-implantation genetic diagnosis.
- Diseases of mtDNA maintenance: Control of mitochondrial copy number may be central to the pathogenesis of mtDNA disorders such as MtDNA depletion syndrome (MDS), Autosomal dominant Progressive External Ophthalmoplegia (AdPEO), Autosomal recessive Progressive External Ophthalmoplegia (ArPEO) and MyoNeuroGastroIntestinal Encephalomyopathy (MNGIE). These newly characterised mtDNA diseases are caused by mutations in autosomal genes, many of which are associated with a reduced quantity of defective mtDNA in affected tissues. We have therefore developed a method for quantitating the rate of mtDNA synthesis in cell lines derived from patients with these diseases. We are using this to study the 16189 variant, autosomally inherited defects in mtDNA maintenance and the basic science of mtDNA replication. We have also used this method to demonstrate consistent abnormalities in mtDNA synthesis in cell lines derived from such patients. Understanding the molecular mechanisms of these disorders may improve genetic counselling, and suggest novel therapies.
- MtDNA variants in common multi-factorial diseases: We demonstrated that a common polymorphism, the mtDNA "16189 variant" is a risk factor for low birth weight to placental ratio, type2 diabetes and other multifactorial disorders. Because the 16189 variant has arisen many times independently, these associations are likely to be causal and not due to a founder effect. We are studying the molecular basis for these associations, which imply interactions of nuclear and mitochondrial genomes.
Routine clinical referrals
DNA diagnostics are carried out in collaboration with theat the Churchill Hospital and detailed characterisation of defects of specific complexes in infants and young children by
Please follow this link to the form that should accompany any samples for DNA analysis that you send: Download Form
From 1st April 2007 this is funded by Rare Mitochondrial Disease Service for Adults and Children (NCG)
Sources of Funding
- Wellcome Trust
Awards Training and Qualifications
- 1996 Royal Society University Research Fellowship
- 1992 Ronnie MacKeith prize, British Paediatric Neurological Association
- 1991 Wellcome Senior Research Fellowship in Clinical Science
- 1997 FRCPCH
- 1991 DM, Oxford University
- 1982 MRCP, London
- 1979 BM BCh, Oxford University
- 1976 BA Physiological Sciences, Oxford University