1. Mutations + Recombination = Genetic Variation!!
Chapter 15: Mutations
Mutations generate genetic variants
These variants are then subject to recombination
Mutations + Recombination = Genetic Variation!!

2. Consequences of Mutations

3. What are the effects of point mutations on gene products?
What would you see in a Northern? In a Western?

4. Are mutations random or induced?
Luria and Delbruck used the “fluctuation test”
They were interested in determining which hypothesis was correct
Conclusion: Mutation can occur in any cell at any time; occurrence is random. (Nobel Prize, 1969)

5. Replica Plating
Repeated identical patterns suggest that the mutation occurred before exposure to phage, and not as a consequence of exposure!

6. What can cause spontaneous mutations?
Errors in DNA replication
Transitions: base pairs mismatch (tautomeric shifts results in mispairing)
Transversions: base pair mismatch with the normal keto base forms

7. What can cause spontaneous mutations?
Errors in DNA replication: Frameshift mutations
(Also known as indel mutations)

8. What can cause spontaneous mutations?
Spontaneous lesions from DNA damage! (depurination, deamination, and oxidative damage)

9. Trinucleotide repeats may lead to disease…why?

10. How can we induce mutations?
Use base analogs
Cause incorrect base pairing

11. How can we induce mutations?
Use intercalating agents which mimic base pairs and slip in between the base pairs…promote indel mutations

12. How can we induce mutations?
Promote base damage
UV light
Ionizing radiation
Promotes large strand breaks
Aflatoxin B1
Binds to guanine and generates an apurinic site

13. Ames Test to Determine Mutagenicity

14. Biological Repair Mechanisms
Direct reversal of damaged DNA
Base-excision repair
Nucleotide-excision repair
Mismatch repair

15. Direct reversal of damaged DNA

16. Base-Excision Repair
Carried out by DNA glycolylases, generate apurininc or apyrimidinic sites
AP endonuclease nicks strand
Deoxyribophosphodi-esterase removes more DNA
DNA polymerase fills in the gap with new DNA

17. Nucleotide-Excision Repair
Used to repair base damage or transcription blocks
Autosomal recessive diseases, Xeroderma pigmentosum and Cockayne Syndrome result from defects in this system

18. Mismatch Repair Recognize mismatch base pairs
Determine which base is the incorrect one
Excise the incorrect base and repair DNA

19. Error Prone Repair
Known as translesion synthesis, requires a bypass polymerase

20. Repair of Double-Strand Breaks
What conditions can cause double strand breaks?
There are two possible situations:
Nonhomologous end joining
Homologous recombination

21. Non-homologous End Joining

22. Homologous Recombination
Damage corrected by synthesis-dependent strand annealing (SDSA)
Uses sister chromatids as templates

23. Why can mutations lead to cancer?
Two types of mutations associated with cancer
Oncogenes are activated
Tumor suppressor genes are inactivated
Genes that control the cell cycle or inhibit apoptosis are considered proto-oncogenes
Tumor Suppressor genes often participate in regulation of cell cycle, activate cell apoptosis, or repair of damaged DNA

24. Chapter 16: Changes in chromosomes

25. Chromosome Numbers
Changes in chromosome sets are known as aberrant euploidy
Changes in parts of chromosome sets is known as aneuploidy

26. Polyploids More common in plants
Correlation between the number of chromosome sets and size of organism
Autopolyploids: multiple chromosomes from one species
Allopolyploids: sets of chromosomes from two or more different species

27. Agricultural Applications
Monoploid plants provide a way to select for desired traits

28. Agricultural Applications
Bananas are sterile triploids
Autotetroploid grapes are larger than diploid grapes

29. Aneuploidy
Mostly due to nondisjunction during meiosis or mitosis

30. Abnormal numbers of sex chromosome
Turner Syndrome
Result of only one sex chromosome (XO)

31. Abnormal numbers of sex chromosome
Klinefleter Syndrome
The result of an extra X chromosome (XXY)

32. Abnormal Number of Autosomes
Down syndrome
Results from an extra copy of chromosome 21

33. Can Down syndrome be inherited?!?

34. Cancer From Translocation

35. Readings for Chapter 15/16 Chapter 15: all sections except 15.5
Chapter 16: section 16.1, 16.2 Robertsonian translocation ( ) and rearrangements and cancer (587)