2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-2

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-3  A change in the nucleotide sequence of a gene  May occur at the molecular or chromosomal level  The effect of mutations vary  Mutant refers to an unusual phenotype  Mutations are important to evolution

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-4  Occur in cells of the body, excluding the germline  Affects subsequent somatic cell descendants  Not transmitted to offspring

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-5 Mutations that occur in the germline cells Possibility of transmission to offspring

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-6  Examples of mutations that cause disease:  Beta globin gene  Collagen  Early onset Alzheimer

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-7  Four globular proteins surrounding heme group with iron atom: two beta chains and two alpha chains  Function is to carry oxygen in red blood cells from lungs to body and carbon dioxide from cells to lungs

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-8 Chapter 12 Opener

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-9 Figure 12.1

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-10  Phenotype associated with homozygotes  Creates sickle shape of RBC  Sickling causes anemia, joint pain, and organ damage when RBC become lodged in small blood vessels

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-11  60% of protein in bone and cartilage  A significant proportion of skin, ligament, tendon, tooth dentin, and connective tissue  Triple helix of two alpha1 and one alpha 2 proteins (2 genes)  Longer precursor, procollagen is trimmed to form collagen

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-12 A mutation prevents procollagen chains from being cut soft, velvety skin that is highly elastic (stretchy) and fragile

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-13  Mutations in presenilin1 cause early onset autosomal dominant Alzheimer disease  Found on Chromosome 14  Presenilin protein is a receptor anchored in the Golgi membrane  Monitors beta amyloid usage  30+ missense mutations in presenilin result in beta amyloid accumulation.

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-14 Figure 12.4

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-15  Change in the DNA  May occur spontaneously or by exposure to a radiation or chemicals  An agent that causes a mutation is a mutagen

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-16  De novo or new mutations  Not caused by exposure to known mutagen  Rare forms of bases exist and are inserted during replication  Purine to purine or pyrimidine to pyrimidine substitution results are transitions  Purine to pyrimidine or vice versa is a transversion

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-17

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-18  Rate differs for different genes  Vary by size  Sequence dependence  Hot spots  On average, 1/100,000 each round of replication  Each individual has multiple new mutations  Most by are not in coding regions of genes

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-19  Alkylating agents  used in creating medicines and industrial specialty  Used in chemotherapy  Acridine dyes  Used to make drugs and dyes  Xrays  UV radiation

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-20  Workplace  Industrial accidents  Chernobyl Chernobyl  Medical treatments  Weapons  Natural sources

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-21  Errors in DNA replication or damage to DNA create mutations  Most errors and damage are repaired  Type of repair depends upon the type of damage or error  Different organisms vary in their ability to repair DNA  In humans, mutations in DNA replication occur in 1 / 100 million bases

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-22  Damaged DNA is removed by excision of the bases  Bases are replaced by a DNA polymerase Nucleotide excision repair  Replaces up to 30 bases  Used in repair of UVB and some carcinogens Base excision repair  Replaces 1-5 bases  Repairs oxidative damage Figure 12.10

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-23  Enzymes detect nucleotides that do not base pair in newly replicated DNA  The incorrect base is excised and replaced  Proofreading is the detection of mismatches Figure 12.11

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-24 Figure 12.12

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-25  Fewer mutations are corrected  Increase in mutations in the genome  The protein p53 monitors repair of DNA  If damage is too severe, the p53 protein promotes programmed cell death or apoptosis  Mutations may occur in genes encoding DNA repair proteins  Lead to overall increase in mutations

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-26  Disorder due to mutations in DNA repair proteins  Results in brittle hair  More severe cases involve delayed development, intellectual disability, infections  Half are photosensitive

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-27  Autosomal recessive, mutation in any of 7 genes  Malfunction of excision repair or deficient “sloppy “ DNA polymerase  Allow thymine dimers to remain and block replication  Must avoid UV light  Rare, only 250 cases worldwide

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-28  3 billion bases  30,000 genes  1.5% of the genome  Genes are located on chromosomes  Humans have 23 pairs (46 total)  22 pairs of autosomes  1 pair of sex

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12-29