1. DNA Mutations and Repair Chapter 17

2. Mutation: is defined as an inherited change in genetic information by cell division or individual organisms. Chernobyl, April 26th, 1986

3. Mutations can be classified into categories. Categories of mutations

4. Somatic and germ line

5. Achondroplasia Autosomal Dominant

6. Gene Mutations can also be classified by type of mutation  1. Base Substitutions □ 2. Insertions and deletions  3. Frameshift mutations  4. Expanding trinuleotide repeats Lead to

7. Gene Mutations can also be classified by type of mutation  Base Substitutions Transitions and Transversions can be

8. PURINE TO PURINE PURINE TO PYRIMIDINE PYRIMIDINE TO PURINE

9. Expanding trinucleotide repeats

10. Fragile X Syndrome Pre-mutation

11. Fragile X syndrome:FMR-1 gene

13. Strand slippage may cause repeats

14. Phenotypic changes and mutations

15. Reverse mutation Forward mutation

16. Forward versus Reverse Mutations

17. Terms associated with PHENOTYPIC effects of mutations on protein structure

18. Phenotypic effects can also change function 1 Sullivan, J.P. et al., Department of Pathology, College of Veterinary Medicine, 1998 The University of Georgia, Athens, GA Gain of Gene Function 1 Loss of Gene Function 2 Qualtek Molecularlabs Web Site or

19. Loss of Function can also occur! Typically recessive mutations!

20. Suppressor Mutations is a genetic change that hides the effect of another mutation

21. Intragenic Suppressor Mutations

22. Intergenic Mutation

23. Lethal Mutations

24. Do you remember something about each type of mutation?

25. This is easy!

26. Mutation Rates and Frequency 1 to 10 mutations per million gametesIncidence within a group

27. Causes of Mutations Spontaneous Induced

28. Environmentally Induced DNA changes

29. Intercalating agents  Insert and distort DNA

30. Radiation Hiroshima (Aug. 6 th, 1945) (Techa River)

32. Thymine Dimers SOS

33. Chemicals and Reactions Leading to Mutations

34. alklyating Deamination Adds OH

35. Oxidative radicals  Reactive forms of oxygen can lead to these radicals

36. Detecting mutations with the AMES test

38. THE AMES TEST Salmonella typimurium

39. AMES TEST  Saccharin  Aflatoxin 2-aminofluorene

40. Aflatoxin B1

41. DNA Repair: general characteristics  Double stranded DNA  Redundancy of pathways

42. Types of DNA repair  Mismatch repair  Direct Repair  Base-Excision Repair  Nucleotide Excision Repair

43. Mismatch repair  Mut H Recognize GATC hemi-methylation  Mut S  Mut L

44. A closer look at mismatch repair

45. Direct Repair DIRECT REVERSAL REPAIR

46. BASE EXCISION REPAIR

48. Nucleotide Excision Repair

49. Diseases of DNA repair!

50. Xeroderma pigmentosum Autosomal recessive

51. Hereditary Non-Polyposis Colon Cancer  HNPCC  15% of all colon cancers

52. Li-Fraumeni  P-53 mutation

54. The End