1. Mutations

2. Sickle Cell Anemia

3. Mutations Can be a change in the DNA base sequence or a change in a chromosome Can be a change in the DNA base sequence or a change in a chromosome Mutant- someone who has a mutation Mutant- someone who has a mutation

4. Consequences of Mutations Mutations can be Mutations can be –Helpful Ex: Give immunity to HIV Ex: Give immunity to HIV Ex: Give immunity to infectious diseases Ex: Give immunity to infectious diseases –Harmless –Harmful Ex: Disease causing mutations (some have to be in homozygous form) Ex: Disease causing mutations (some have to be in homozygous form)

5. What do Mutations do? Can stop or slow the production of a protein Can stop or slow the production of a protein –Ex: Cause a protein to overproduce Cause a protein to overproduce –Ex: Impair a protein’s function Impair a protein’s function –Ex:

6. When can Mutations happen? Germline mutation- happens before meiosis; affects all cells in the new organism Germline mutation- happens before meiosis; affects all cells in the new organism Somatic mutation- happens before mitosis; after only immediate daughter cells and their descendents Somatic mutation- happens before mitosis; after only immediate daughter cells and their descendents –More severe the earlier it occurs –Creates a mosaic –Can lead to some forms of cancer

8. Spontaneous Mutations Spontaneous Mutations Change occurs with no outside influence Change occurs with no outside influence Often occurs because of a mismatch in base pairs during replication Often occurs because of a mismatch in base pairs during replication Results in de novo mutations Results in de novo mutations

9. Mutation Rates Different in different genes Different in different genes Depends on Depends on –Gene size –Gene location –Gene sequence

10. Mutation Hot Spots Sequence Regions Sequence Regions –That are repetitive –Symmetrical or repeated sequences on the same strand –Palindromes- sequence that reads the same forward and backward Sections confuse replication enzymes

11. Mutagen Substance causing a mutation Substance causing a mutation –Chemicals –Radiation Exposure can be accidental or purposeful Exposure can be accidental or purposeful It can also come from the natural environment It can also come from the natural environment

12. Huntington’s Disease

13. Types of Mutations Point mutations- change of a single base Point mutations- change of a single base –Transition- exchange of one pyrimidine for another or one purine for another –Transversion- exhange of a pyrimidine for a purine or vice versa –Missense mutation- changes one amino acid in polypeptide chain –Nonsense mutation- creates a stop codon in the middle of the polypeptide chain Nonsense mutationNonsense mutation –Splice site mutations- alters the splicing of the pre-mRNA

14. Types of Mutation (cont) Frameshift mutations- move the reading frame; can be point mutations; all amino acids after mutation can be affected Frameshift mutations- move the reading frame; can be point mutations; all amino acids after mutation can be affected Frameshift mutations Frameshift mutations –Insertion- addition of bases Tandem duplication- repetition of a sequence placed very close to the original Tandem duplication- repetition of a sequence placed very close to the original –Deletion- removal of bases

16. Expanding Repeats Repeated section of DNA is replicated incorrectly causing extra repeats Repeated section of DNA is replicated incorrectly causing extra repeats Repeats are added to during every generation (higher severity; earlier onset) Repeats are added to during every generation (higher severity; earlier onset) Repeats often create symptoms when they reach higher than 40 Repeats often create symptoms when they reach higher than 40

17. Wild type "Normal Gene" THE ONE BIG FLY HAD ONE RED EYE MissenseTHQ ONE BIG FLY HAD ONE RED EYE NonsenseTHE ONE BIG FrameshiftTHE ONE QBI GFL YHA DON ERE DEY DeletionTHE ONE BIG HAD ONE RED EYE DuplicationTHE ONE BIG FLY FLY HAD ONE RED EYE InsertionTHE ONE BIG WET FLY HAD ONE RED EYE Expanding(P) THE ONE BIG FLY HAD ONE RED EYE Expanding (F1) THE ONE BIG FLY FLY FLY HAD ONE RED EYE Expanding (F2) THE ONE BIG FLY FLY FLY FLY FLY FLY HAD ONE RED EYE

18. Other Causes of Mutations Pseudogenes Pseudogenes –Replicate of gene made at earlier time –Currently not used (collected enough mutations) –May still be close enough to cross over with real gene causing mutations in real gene Transposons (jumping genes) Transposons (jumping genes) –Jump into working gene causing mutation

19. Xeroderma Pigmentosum

20. Minimizing the Effects of Mutation Position Position –Change in third position often does nothing –Change in second position often either does nothing or changes one amino acid for a similar one Conditional mutation Conditional mutation –Mutation only affects the phenotype under certain phenotype under certain conditions conditions Stem cell DNA Stem cell DNA –Stem cell may retain old template DNA strands and send new strands into progenitor cell

21. DNA Repair: Photoreactivation DNA is damaged by UVB wavelengths DNA is damaged by UVB wavelengths Forms thymine dimers Forms thymine dimers –extra covalent bond between thymines next to each other on the same strand –forms kinks in DNA; disrupts replication and transcription Enzymes called photolyases absorb energy from light and break these bonds Enzymes called photolyases absorb energy from light and break these bonds Humans do not use this Humans do not use this

22. DNA Repair: Excision Repair Enzymes snip out section with pyrimidine dimers Enzymes snip out section with pyrimidine dimers DNAP fills in gap with correct nucleotides DNAP fills in gap with correct nucleotides Humans have two types Humans have two types –Nucleotide excision repair Used for many types of damage Used for many types of damage Repairosome- group of enzymes that cut out and replace up to 30 nucleotides Repairosome- group of enzymes that cut out and replace up to 30 nucleotides –Base excision repair Used for oxidative damage Used for oxidative damage Replaces up to 5 nucleotides at a time Replaces up to 5 nucleotides at a time

23. Nucleotide Excision Repair

24. Base Excision Repair

25. DNA Repair: Mismatch Repair Repairs errors that occur because of replication Repairs errors that occur because of replication Enzymes look for loops in DNA (sign of mismatching) and cut out and repair bases Enzymes look for loops in DNA (sign of mismatching) and cut out and repair bases