1.05 - Mitochondrial Genome & Mutations

Question 1

What do the genes in the mitochondrial genome encode?

Answer 1

Proteins involved in oxidative phosphorylation (energy production)
Transfer RNA
Ribosomal RNA

Question 2

Describe mitochondrial inheritance

Answer 2

Mitochondria present in gametes, so contents of the mitochondrial genome is passed down to offspring.
Approximately 100,000mitochondria/egg & 100 per sperm.
Highly debated if any mtDNA is transferred to offspring from the father, if any it is negligible.
Therefore only maternal mitochondrial inheritance can occur

Question 3

Describe why mutations are more likely in mitochondrial DNA

Answer 3

No repair mechanisms in mitochondrial DNA
Increased exposure to free radicals as these are produced during oxidative phosphorylation.
This leads to increased accumulation of mutations in mtDNA compared to nuclear DNA.

Question 4

What cells are most likely to be effected by mitochondrial DNA mutations?

Answer 4

The number of mitochondria in a cell is proportional to the energy demands of that cell. More energy –> more mitochondria. Therefore cells with the highest energy demand (neural cells) will be most effected by mutations in mtDNA. Most diseases due to mitochondrial DNA mutations will effect the brain and nervous system

Question 5

Define: Penetrance

Answer 5

Penetrance is the proportion of individuals carrying a particular variant of a gene that also expresses an associated trait.
Huntington’s: 100% penetrance
BRCA1 - variable penetrance - ~60%

Question 6

Define: Expressivity

Answer 6

Expressivity is a term used to refer to variations in a phenotype among individuals carrying a particular genotype. “Severity of a disease trait?”
Huntington’s –> Anticipation
Cystic Fibrosis - Severity of lung disease

Question 7

Describe the genetics of Haemochromatosis

Answer 7

Mutation in Human Haemochromatosis Protein (HFE). Autosomal recessive inheritance. 2 predominant mutations (C282Y & H63D).
Different mutations have different penetrance
Different mutations can also have different expressivity

Question 8

What is variable expressivity?

Answer 8

Expressivity refers to variations in a phenotype among individuals carrying a particular genotype. An example is Marfan syndrome (autosomal dominant). Patients, can have a variety of particular symptoms.