Medical Genetics ■●●●●■● Male with normal mitochondrial genes Female with normal mitochondrial genes Male with mitochondrial disease gene Female with mitochondrial disease gene
Medical Genetics
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 muscle
Medical 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
Medical Genetics Mitotic segregation %o of mutant mtDNAs in daughter cells can shift at cell division Produces rapid changes of genotype that may lead to crossing of threshold
Medical Genetics Mitotic segregation –% of mutant mtDNAs in daughter cells can shift at cell division – Produces rapid changes of genotype that may lead to crossing of threshold
Medical Genetics There are many forms of mitochondrial disease. mitochondrial disease presents very differently from individual to individual
Medical Genetics There are many forms of mitochondrial disease. Mitochondrial disease presents very differently from individual to individual
Medical Genetics Mitochondrial disease is inherited in a number of different ways There may be one individual in a family or many individuals affected over a number of generations
Medical Genetics Mitochondrial disease is inherited in a number of different ways. There may be one individual in a family or many individuals affected over a number of generations