1. MITOCHONDRIAL GENETICS

2. 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

3. Nuclear (Cellular) Chromosomes 3.2 billion total nucleotide pairs MitochondrialChromosomes 2-10 @ per mito 1000-10000 per cell 0.32-1.6 billion total nucleotide pairs total nucleotide pairs

5. 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

7. Ataxia v. Ataxia

9. 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

10. 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

11. 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

12. 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

15. Maternal Transmittance of Mitochondrial Disease

16. heteroplasmy

17. 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

18. At the course download site: mitogenetics.ppt