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Mitochondrial DNA Mutations and Human Disease

Department of Clinical Neurosciences

About the Project

This project aims to determine the burden of inherited neurogenetic conditions in consanguineous marriages in Turkey and thereby develop and improve genetic diagnosis and understanding of severe and chronic disorders in childhood affecting primarily the brain, the nervous system and skeletal muscle.
Expert paediatric neurologists in Turkey carried out detailed clinical investigations of around 250 children from consanguineous families with severe childhood disorders of the brain, nervous system or muscle and obtained blood and skin biopsy samples from these children as well as their unaffected parents and affected or unaffected siblings. DNA has undergone whole exome sequencing followed by in-depth computer analysis. Potential genetic causes in relevant genes have been identified and will be further explored to establish their function and prove whether these variants are indeed the cause of the child’s condition.
The scientific work will be carried out in this project and involves bioinformatics analysis of exome datasets as well as the use of stem cell technology to transform skin cells into nerve cells. We also perform genetic manipulations in zebrafish embryos to model the genetic defect and to better understand the function of the gene in the nervous system. Exploring these aspects in human cells and fish allows research towards the development of targeted and effective treatments for these diseases in humans. In addition to the expected discovery of new disease-causing genes, we will also generate and share valuable data on consanguineous families in Turkey, which will help to understand the impact of consanguinity on severe childhood disorders in populations with high consanguinity rates.

Funding Notes

Funding deadline is 3rd December 2020 for start in October 2021. When applying indicate on the application the funding options (GATES USA *deadline 14/10/20*, Gates Cambridge or other Cambridge Funders). Home/EU and International applications are all considered for funding.


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Bansagi B, Griffin H, Whittaker RG, Antoniadi T, Evangelista T, Miller J, Greenslade M, Forester N, Duff J, Bradshaw A, Kleinle S, Boczonadi V, Steele H, Ramesh V, Franko E, Pyle A, Lochmüller H, Chinnery PF, Horvath R. Genetic heterogeneity of motor neuropathies. Neurology 2017;28;88(13):1226-1234.
Boczonadi V, Müller V, Pyle A, Munkley J, Dor T, Quartararo J, Ferrero I, Karcagi V, Giunta M, Polvikoski T, Birchall D, Princzinger A, Cinnamon Y, Lützkendorf S, Piko H, Reza M, Florez L, Santibanez-Koref M, Griffin H, Schuelke M, Elpeleg O, Kalaydjieva L, Lochmüller H, Elliott DJ, Chinnery PF, Edvardson S and Horvath R. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat Commun 2014;5:4287.
Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski-Feder E, Abicht A, Czermin B, Kleinle S, Morris AAM, Vassallo G, Gorman GS, Turnbull DM, Ramesh V, Santibanez-Koref M, McFarland R, Horvath R, Chinnery PF. Whole exome sequencing defines the genetic basis of multiple mitochondrial respiratory chain complex deficiency. JAMA 2014;312:68-77.

Applicants can only be considered if they apply via the applicant portal which can be found at this link; please do not send in an enquiry and CV as this will not be considered an application.

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