MITOCHONDRIAL GENETICS
Origin of Mitochondria
Endosymbiont Theory
• Similar size to certain free-living bacteria
• Similar chromosome & cytoplasm to
bacteria
• Similar ribosomes to bacteria
• Similar cell division to bacteria
• Independent replication & gene expression
Mitochondrial
Chromosomes
2-10 @ per mito
1000-10000 per cell
Nuclear (Cellular) Chromosomes
3.2 billion total nucleotide pairs
0.32-1.6 billion
total nucleotide pairs
Genetically
Controlled
Processes
in Mitochondria
• 13 genes for respiratory chain proteins
• Subunits of the ATPase complex
• Subunits for the NADH-dehydrogenase complex
• 22 genes for tRNAs
• 2 genes for rRNAs
• Maintenance of cellular energy levels
Ataxia v. Ataxia
Human Mitochondria
• 2-10 chromos per mito
• 13 protein-encoding regions
• 3 subunits of cytochrome c oxidase
complex
• Cytochrome b complex
• 2 subunits of the ATPase complex
• 60% occupied by six subunits of
NADH dehydrogenase complex
• 22 tRNAs
• 2 rRNAs
• other
Stability of Mitochondrial DNA
• Mutatation rate 10X higher than
nuclear DNA
• Mutations generated by oxidation
by-products
• No protective histones
• Ineffective DNA repair
• Typically point mutations or
deletions
• Tolerance for deletions variable
• Some deletions recurring in
unrelated patients
Mitochondrial Diseases
General Characteristics
•
•
•
•
•
Penetrance usually complete (100%)
Expressivity highly variable
Age of onset variable
Frequently limited to specific tissues
Usually appear as reduced muscle strength
together with degeneration of other tissues
• Affects organs with high energy requirements:
brain, heart, skeletal muscle, eye, ear, liver, pancreas, and kidney
Some Mitochondrial Diseases
• Kearns-Sayre syndrome
opthalmoplegia, retinal degeneration, cardiomyopathy
• Lactic-Acidosis-Encephalomyopathy-Stroke
syndrome
• Neurogenic muscle weakness with ataxia and
retinitis pigmentosa syndrome
• Pearson syndrome
bone marrow and pancreas failure
• Diabetes-deafness syndrome
Maternal Transmittance of Mitochondrial Disease
heteroplasmy
Mitochondrial Diseases
General Characteristics
•
•
•
•
•
Penetrance usually complete (100%)
Expressivity highly variable
Age of onset variable
Frequently limited to specific tissues
Usually appear as reduced muscle strength
together with degeneration of other tissues
• Affects organs with high energy requirements:
brain, heart, skeletal muscle, eye, ear, liver, pancreas, and kidney
At the course download site:
mitogenetics.ppt