lec 4 SAQ - Mitochondrial Genetics and Inherited Disorders Quiz

16,569 bp

37

93%

Dozens

Several different individuals

About 3000

Mitochondria are the 'powerhouses' of the cell, responsible for generating ATP and involved in cell signalling, growth, death, and cell cycle regulation.

Mitochondria are thought to have originated as free-living bacteria that were taken up by eukaryotes to carry out oxidative phosphorylation.

Most nucleated cells contain 500 to 2000 mitochondria.

In the cone cell photoreceptor of the eye, mitochondria make up 80% of the intracellular volume.

The human nuclear genome contains approximately 23,000 protein-coding genes.

The human nuclear genome consists of 23 double-stranded linear chromosomes.

Mitochondrial heteroplasmy refers to the variation in mtDNA sequences, either between cells (intercellular heteroplasmy) or within cells (intracellular heteroplasmy).

Mitochondrial DNA is inherited almost exclusively along the maternal line.

The threshold effect refers to the proportion of pathogenic mtDNA in tissues, which influences the phenotypic expression of mitochondrial diseases.

MtDNA mutation represents the only source of mtDNA genetic diversity, as mitochondria do not undergo recombination during cell division.

The control region of mtDNA is highly polymorphic and is useful for forensic purposes, such as in criminal investigations.

Homoplasmy refers to all mtDNA sequences being the same, while heteroplasmy refers to variation in mtDNA sequences.

Predicting phenotype from genotype and genetic counseling is difficult in mitochondrial heteroplasmy because the proportion of pathogenic mtDNA in tissues can vary and influence the phenotype.

Mitochondrial disease often affects high-energy organ systems such as the CNS, muscles (skeletal and heart), liver, and kidney.

Bilateral, painless, subacute visual failure that develops during young adult life.

Males are approximately four times more likely to be affected than females.

The typical symptoms of LHON include asymptomatic onset in one eye followed by similar symptoms in the other eye, bilateral visual loss, and in some cases, central vision improvement but incomplete recovery.

The three point mutations of mitochondrial DNA commonly associated with LHON are m.3460G>A in MT-ND1, m.11778G>A in MT-ND4, and m.14484T>C in MT-ND6.

Individuals with the m.11778G>A mutation typically have an intermediate phenotype and there is a chance of recovery.

Heteroplasmy refers to the presence of both normal and mutated mitochondrial DNA in an individual. In LHON, heteroplasmy in cone cells may influence the risk of developing visual impairment.

Haplogroup H is associated with higher risk of Parkinson Disease, while haplogroups J and K are associated with lower risk. Haplogroups I, J, and T are also associated with increased longevity.

No, mitochondrial DNA inheritance can also occur through biparental inheritance in some exceptional cases.

Leigh Syndrome is characterized by MRI necrotizing lesions in the midbrain and brainstem, bilateral symmetrical degeneration of the brain stem, cerebellum, and basal ganglia. It typically has an onset in infancy or childhood, often after a viral infection, and can involve peripheral nervous system involvement, non-neurologic abnormalities, and respiratory impairment.

The estimated incidence of Leigh Syndrome is at least 1 in 40,000 births.

Leigh Syndrome exhibits broad genetic heterogeneity, with mutations identified in at least 75 genes.

Some of the genetic mutations associated with Leigh Syndrome include mutations in pyruvate dehydrogenase (PDHC) deficiency, respiratory chain enzyme defects in complexes I, II, IV, and V, and specific mtDNA mutations such as the NARP mutation and the MERRF mutation.

Leigh Syndrome can be inherited in matrilineal (mitochondrial) pattern, de novo mutation, X-linked recessive, or autosomal recessive patterns.

The different inheritance patterns in Leigh Syndrome are primarily due to the fact that most mitochondrial proteins are encoded on the nuclear genome, and mutations in these genes follow classic Mendelian inheritance rules.

Mitochondrial transplantation/donation is a technique that involves the transfer of healthy mitochondria to prevent the passing on of hereditary mitochondrial diseases. It can be performed before or after fertilization and has been the subject of ethical debates, including a UK parliamentary debate in 2015.

Some important factors to remember about mitochondrial genetics are: 1. Predicting phenotype from mtDNA genotype is difficult due to heteroplasmy. 2. Males affected by mtDNA-related diseases cannot transmit the disease. 3. mt Haplogroups can influence disease penetrance and severity. 4. Most Leigh Syndrome cases are caused by mutations in the nuclear genome, leading to Mendelian inheritance patterns.