1. Gene Mutation *Mutation Chromosome mutations/aberrations Classification of Mutations 1. Spontaneous vs. Induced Spontaneous mutation Induced mutation 2. Gametic vs. Somatic Somatic mutation Gametic mutation 3. Other categories

2. Gene Mutation How are mutations detected in humans? *Pedigree analysis *Cells cultured in vitro Analysis of enzyme activity, sequencing of proteins and DNA The molecular basis of mutation (Point mutations) 1. Base substitution transition transversion 2. Frame shift 3. Tautomeric shift 4. Base analogs 5. Chemical mutagens

3. Gene Mutation The molecular basis of mutation (Structural damage) 1. Missing bases N-glycosidic bond – very weak and easily broken 2. UV light – thymine/thymine dimers 3.Ionizing radiation

4. Gene Mutation Mutations in humans ABO Blood Types A A A A A A A B B A B B B B A B A B A B A A Genotype: I A I A, I A I O I B I B, I B I O IAIBIAIB IOIOIOIO “H substance” glycosyltransferase A “H substance” glycosyltransferase B 4 nucleotide differences “H substance” X Frame-shift=non-functional protein

5. Gene Mutation DNA Repair 1. Photoreactivation *PRE – photoreactivation enzyme

6. Gene Mutation DNA Repair 2. 3’ to 5’ exonuclease activity of DNA polymerases 3. Excision repair (BER)

7. Gene Mutation 3. Excision repair

8. Gene Mutation 4. Post-replication repair (recombination repair) recombined

9. Gene Mutation 5. Inducible repair or SOS (prokaryotes) *”It’s better to be a mutant than be dead!”