Genetics
Mitochondrial Inheritance
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Get accessEach cell has extranuclear chromosomes within mitochondria (about 10 single circular chromosomes)
- 0.5% of total DNA
- These replicate independently of the nuclear genome
- This DNA has no introns
Genes encode for tRNA and ribosomal RNA required for mitochondrial protein synthesis and proteins involved in cellular oxidative phosphorylation
- Mitochondrial DNA has a higher mutation rate than nuclear DNA
- The DNA polymerases here are highly inaccurate
- Mitochondrial DNA is much more susceptible to oxidative damage
- Alkylating agents affect mtDNA much more effectively
- Repair mechanisms are underdeveloped for mtDNA
- With no introns, mutations are likely to impact a coding sequence
Sperm lose their acrosome during fertilisation (they are rich in mitochondrial DNA before this)
- Therefore mitochondrial chromosomes are inherited exclusively from the female ova
- Males cannot transmit
- Both males and females can be affected if their mother has the defective gene
An affected mother passes the defect to all her children but only daughters will transmit
Mitochondrial DNA is distributed between several mitochondria in a cell, therefore normal and abnormal DNA can coexist: so-called heteroplasmy
The proportion of abnormal DNA needed to produce a disease phenotype creates the “threshold effect”
- Disease severity is therefore variable and some children may not be manifestly affected
Hot Topic
Mitochondrial diseases
- Leber’s hereditary optic neuropathy
- Kearns-Sayre syndrome
- MIDD (maternally inherited diabetes mellitus and deafness)
- MELAS
- Myoclonic epilepsy with ragged red fibre
- Zidovudine induced acquired mitochondrial myopathy