The role of mitochondria in common disease


  1. Fine mapping chromosome 3q in relation to metabolic traits and common myopiaThe quantitative trait locus (QTL) on chromosome 3q influences a number of related metabolic traits (including insulin resistance) and is one of the most replicated human quantitative trait linkages to be studied. 3q also shows replicated evidence of linkage and association for common myopia in this region. This study aims to identify the genes responsible for these linkage signals and further fine map the association signals already identified. On the back of this large mapping project, follow-up studies include:
    • Association between common myopia and regulatory long ncRNA in the SOX2 region
    • A fine-mapping study of the biotin-dependent carboxylase gene family


  2. Heteroplasmy study: mitochondrial DNA sequencing projectIt is hypothesized that the mitochondrial mutational load is both associated with and a potential cause of morbidity. Heteroplasmy (the presence of both wild type and mutant mtDNA in single cell or tissue) will be used to assess mutational load across the mitochondrial DNA molecule. Approximately 500 individual twins are currently being 454 sequenced (x300 coverage) at the Sanger for mtDNA extracted from blood to facilitate a number of exciting studies including:
    • A case-control association study of heteroplasmy and type 2 diabetes (100 unrelated cases and 200 controls individually matched for sex, age and BMI using a 1:2 design). In addition, 40 MZ pairs discordant for T2D are being sequenced to estimate the prevalence of somatic heteroplasmy
    • A classical twin study of heteroplasmy bottlenecks and mutation rates (100 co-twins of the controls will also be sequenced; a total of 50 DZ and 50 MZ pairs)
    • The impact of different haplo-groups on metabolic and myopia traits


  3. Mitochondrial morphology pilot studyA case-control comparison of mitochondrial morphology using EM images from chick retina from eyes with lens induced myopia (4 cases, -10D lenses for 4 days) and normal vision (4 controls)


Medical Research Council


2010 – 2013