1. Instability: Mutation and DNA repair
Mutations
DNA repair

2. Instability: Mutation and DNA repair
Substitution rates vary throughout the genome.

4. Instability: Mutation and DNA repair
Different mutation rates in primates and rodents
Species Pair Sites Percent Divergence Substitution rate (x 109)
Human/Chimp (7 myr)
Human/Old world monkey (25 myr)
Mouse/rat (15 myr)

5. Instability: Mutation and DNA repair
Higher mutation rates in males
Greater number of cell divisions

7. Instability: Mutation and DNA repair
Sex-specific differences in mutation rates
Gene Mutation Ratio of male/female mutations
NF1 Point 4.5
VHL Point 1.3
RB Point 8.5
ZFX/ZFY Mutations in last intron 6

8. Instability: Mutation and DNA repair
Mechanism of mutation
Simple sequence repeats and strand slippage

11. Instability: Mutation and DNA repair
Mechanism of mutation
Homologous equal crossover yields fusion genes.

13. Instability: Mutation and DNA repair
Mechanism of mutation
Unequal crossover causes insertions and deletions.

15. Instability: Mutation and DNA repair
Mechanism of mutation
Unequal crossover in a tandem repeat array can result in sequence homogenization.

17. Instability: Mutation and DNA repair
Mechanism of mutation
Tandem gene duplication by unequal crossover or sister chromatid exchange facilitated by short interspersed elements.

19. Instability: Mutation and DNA repair
Mechanism of mutation
Gene conversion
Non reciprocal sequence exchange between allelic or nonallelic genes.

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23. Instability: Mutation and DNA repair
Mechanism of mutation
Splicing mutations
Intron retention
Exon skipping
Activation of cryptic splice sites

26. Instability: Mutation and DNA repair
Mechanism of mutation
Short tandem repeats are deletion insertion hotspots.

28. Instability: Mutation and DNA repair
Mechanism of mutation
Spinocerebellar ataxia (SCA1) triplet repeat expansion.

30. Instability: Mutation and DNA repair
Mobile elements and mutations
Alu element
Insertion events
Recombination events

31. Reverse transcription and insertion
Pol III transcription
1. Usually a single ‘master’ copy
2. Pol III transcription to an RNA intermediate
3. Target primed reverse transcription (TPRT) – enzymatic machinery provided by LINEs

33. What are SINEs? 1. Interspersed Elements 2. 70 - 300 Bases in Length
3. Very High Copy Numbers
(>100,000 Copies/Genome)

41. Instability: Mutation and DNA repair
Photodimer
DNA glycosylase /AP endonucleases
E-coli mismatch repair
Human mismatch repair

42. Instability: Mutation and DNA repair
Photodimer

44. Instability: Mutation and DNA repair
DNA glycosylase /AP endonucleases

46. Instability: Mutation and DNA repair
E-coli mismatch repair
Human mismatch repair

49. Instability: Mutation and DNA repair
Human mismatch repair