I am a Wellcome Career Re-entry fellow, investigating the complex interactions between mitochondrial and nuclear genetic variations and their impact on mitochondrial disease.
I joined the mitochondrial research group in November 2015, after a ten year break from research, and have a background in complex disease genetics, having completed my PhD and Wellcome Prize Fellowship at the Wellcome Trust Centre for Human Genetics in Oxford. My project applies the concepts of complex disease genetics to the question of phenotypic variability in mitochondrial disease. I use clinical and genetic data from individuals who carry the mitochondrial DNA mutation m.3243A>G in order to identify nuclear genetic variation that modifies clinical phenotype. Understanding what causes the vast clinical variability in m.3243A>G-related disease will give patients and clinicians a much better idea of disease prognosis, enabling improved genetic counselling and advice.
Identification of nuclear factors modulating the clinical phenotype of m.3243A>G-related mitochondrial disease
Principal Investigators: Dr Sarah Pickett
Other staff members involved: Professor Robert Taylor, Professor Sir Doug Turnbull, Professor Heather Cordell (Institute of Genetic Medicine), Dr. Ian Wilson (Institute of Genetic Medicine), Roisin Boggan.
The m.3243A>G mtDNA mutation causes a devastating syndrome which can result in uncontrolled seizures, strokes and early death, however, large numbers of m.3243A>G-carriers have different symptoms, including diabetes and deafness. m.3243A>G can affect any organ, at any age and with any degree of severity. Family studies suggest that nuclear variation influences clinical outcome. My project aims to identify these using a unique group of more than 400 m.3243A>G carriers by:
- Searching nuclear chromosomes for regions shared more frequently in patients with similar symptoms (whole genome family-based linkage analysis and whole cohort-based association analysis).
- Sequencing nuclear DNA to identify variations that cause differences in clinical outcome.
- Characterising variants, showing how they cause these differences.
- Developing statistical models to estimate disease outcome based on genetic risk factors
The discovery of genetic risk factors for m.3243A>G-related disease will improve our understanding of this common mitochondrial disease and allow clinicians to tailor patient treatment and advice.
Sponsor/Funder: The Wellcome Trust