1. Gene Mutation

2. Mutation Mutation: change in DNA sequence Causes of mutation: Spontaneous Due to naturally- occurring errors in DNA replication Induced Due to exposures to radiation or chemical mutagens

3. Spontaneous Mutation

4. Spontaneous mutation in gene for a blood clotting factor, leading to hemophilia.

5. Point Mutations Point mutation: change in one or a few DNA nucleotides Substitution One nucleotide is replaced by another Deletion One or more nucleotides are removed Insertion One or more nucleotides are added Duplication Nucleotides are repeated within a gene

6. Substitutions NameSubstitutionExample Transition change to same type of base Purine  purine Pyrimidine  pyrimidine AT  GC Transversion change to different type of base Purine  pyrimidine Pyrimidine  purine AT  CG

7. Examples of Substitutions TransitionTransversion DNA Top strand is template 3’-T-T-C-5’5’-A-A-G-3’3’-T-C-C-5’5’-A-G-G-3’3’-T-T-C-5’5’-A-A-G-3’3’-T-G-C-5’5’-A-C-G-3’ RNAcodon5’-A-A-G-3’5’-A-G-G-3’5’-A-A-G-3’5’-A-C-G-3’ Amino Acid Acidlysineargininelysinethreonine

8. Effects of Substitutions on the Protein Sequence TypeDefinitionExample (codons are shown) Silent Change to a different codon for the SAME AMINO ACID AGG  CGG Arg Arg Synonymous Change to a chemically- SIMILAR AMINO ACID AAA  AGA Lys Arg Missense Change to a chemically- DIFFERENT AMINO ACID AAA  GAA Lys Glu Nonsense Change to a stop codon, SHORTENS THE PROTEIN CAG  UAG Gln Stop

9. Applying Your Knowledge The mutation that leads to Sickle-cell Disease (Hb S ) is a The mutation that leads to Sickle-cell Disease (Hb S ) is a 1.Silent Mutation 2.Synonymous mutation 3.Missense Mutation 4.Nonsense Mutation 5.None of these Hb S Hb A

10. Applying Your Knowledge The mutation that leads to the insertion of valine into Hb S is due to a The mutation that leads to the insertion of valine into Hb S is due to a 1.Transition 2.Transversion 3.Both a transition and a transversion 4.Neither a transition nor a transversion Hb S

11. Frameshift Mutations Frameshift mutation: deletion or insertion of nucleotide bases, not in multiples of three Causes a change in the “reading frame” of codons for the protein sequence Original Codon Sequence Original Codon Sequence Amino acid sequence AAG-ACU-UAC-CAALys---thr---tyr---gln Frameshift due to insertion Amino acid sequence AA(A)-GAC-UUA-CCA-ALys----asp---leu---pro

12. Insertions in multiples of three nucleotides restore the reading frame.

13. Tandem Duplications Tandem duplications: adjacent or nearby repeat of part of a gene’s sequence Charcot-Marie- Tooth Disease Repeat of 1.5 million base pairs within gene Disorder of nervous system that affects nerves directed to muscles in hands and feet. Causes a numbing of hands and feet, difficulty walking

14. Expanding Triplet Repeats Expanding Triplet Repeats: increase in number of a specific trinucleotide within a gene from generation to generation Huntington Disease Repeat of CAG triplet leads to repeat of glutamine in the protein Huntingtin. Neurodegenerative disorder leading to personality changes and uncontrollable movements.

15. Allen (46,13) age 50 Linda (6,22) Kristen (64,22) age 40 Ann (64,22) age 39 Andrew (69,6) age 37 Debbie (13,6) Greg (11,19) Nathaniel (72,19) age 35 Bill (8,12) Paula (13,12) Evan (not tested) Christina (93,7) age 26 Joseph (7,6) Jama (7,18) Expansion of the Trinucleotide Repeat for Huntington’s Disease

16. Applying Your Knowledge A.An insertion of one or two nucleotide bases causes a _____. B.Replacing one nucleotide with another causes a ____. C.A repeat of part of a gene’s sequence in a nearby region is a ______. 1. Substitution 2. Frameshift Mutation 3. Tandem Duplication 4. Expanding Triplet Repeat

17. Repair of DNA Type of Damage Repair Mechanism Ultraviolet Light Causing Thymine-Thymine Dimers Photoreactivation Damage caused by chemicals or ultraviolet light Excision Repair Incorrect base inserted in new strand during replication Mismatch Repair Mismatch Repair

18. Repairing UV-Damaged DNA Use of enzymes to remove and replace region with thymine- thymine dimer Use of light and enzymes to reverse thymine- thymine dimers

19. Photoreactivation

20. Mismatch Repair: Correcting Errors in DNA Replication

21. Xeroderma Pigmentosum: Accumulation of DNA Damage Leads to Skin Cancer

22. Applying Your Knowledge A.Method of replacing a DNA region that was damaged by radiation or chemicals B.Method that uses white light to repair thymine- thymine dimers produced by ultraviolet radiation C.Method of replacing DNA region where a nucleotide was incorrectly placed during replication 1. Mismatch Repair 2. Excision Repair 3. Photoreactivation