Medical Genetics Threshold effect oo of mutant mtdNas must be above a threshold to produce clinical manifestations %o of mutant mtDNAs needed to cause cell dysfunction varies according to tissue oxidative requirements o Disease signs especially manifest in Tissues with a high energy expenditure Dependent on oxidative metabolism Specific tissues: Brain Heart muscleMedical Genetics Threshold effect • % of mutant mtDNAs must be above a threshold to produce clinical manifestations • % of mutant mtDNAs needed to cause cell dysfunction varies according to tissue oxidative requirements • Disease signs especially manifest in – Tissues with a high energy expenditure: Dependent on oxidative metabolism – Specific tissues: Brain, Heart & Muscle