复旦大学：《医学遗传学 Medical Genetics》课程教学资源（PPT课件讲稿）线粒体疾病 mitochondrial diseases

Medical Genetics 线粒体疾病 mitochondrial diseases

Medical Genetics 线粒体疾病 mitochondrial diseases

Medical Genetics Mutations(changes)in the mitochondrial chromosome are responsible for a number of disorders

Medical Genetics Mutations (changes) in the mitochondrial chromosome are responsible for a number of disorders

Medical Genetics Mitochondrial disease is a chronic genetic disorder that occurs when the mitochondria of the cell fails to produce enough energy for cell or organ function

Medical Genetics Mitochondrial disease is a chronic, genetic disorder that occurs when the mitochondria of the cell fails to produce enough energy for cell or organ function

Medical Genetics The incidence about 1: 3000-4000 individuals in the us

Medical Genetics The incidence about 1:3000-4000 individuals in the US

Medical Genetics Characteristics Unlike nuclear genes, which are inherited from both parents, mitochondrial genes are inherited only from the mother In mammals, 99. 99% of mitochondrial DNA(mtDNA) is inherited from the mother This is because the sperm carries its mitochondria around a portion of its tail and has only about 100 mitochondria compared to 100,000 in the oocyte

Medical Genetics Characteristics Unlike nuclear genes, which are inherited from both parents, mitochondrial genes are inherited only from the mother. In mammals, 99.99% of mitochondrial DNA (mtDNA) is inherited from the mother. This is because the sperm carries its mitochondria around a portion of its tail and has only about 100 mitochondria compared to 100,000 in the oocyte

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