1. Mutations, DNA replication, Cancer
A single mutation caused this

2. Cystic fibrosis (accumulation of mucus in lungs) is due to a ___
A. Faulty lysosome B. Faulty cell membrane C. Faulty cytoskeleton D. All of the above

3. Review of Protein Synthesis
Genetic information flows in cell from
DNA  RNA  protein.
Each gene on DNA codes for production of a specific polypeptide/protein.

4. Mutations

5. Cancer Breast Cancer Two human genes, called BRCA1 and BRCA2
>200 different changes in the DNA sequences

6. Sickle cell Anemia

7. Mutation: A change in the nucleotide sequence of DNA.

8. Mutation: A change in the nucleotide sequence of DNA.
Causes of mutations
Given the potentially hazardous health consequences of mutations, it is advisable to minimize their occurrence. Can this be done? Yes and no. There are three chief causes of mutation, and although one of them is beyond our control, the other two can be significantly reduced.
1. Spontaneous mutations. Some mutations arise by accident as long strands of DNA are duplicating themselves—at the rate of more than a thousand bases a minute in humans—when cells are dividing. Most errors are repaired by DNA repair enzymes, but some still slip by, and there’s not much we can do about them.
2. Radiation-induced mutations. Ionizing radiation is radiation with enough energy that it can disrupt atomic structure—even breaking apart chromosomes—by removing tightly bound electrons. Sources of ionizing radiation include X-rays and the ultraviolet rays of the sun. When you lie in the sun, for example, its ultraviolet rays can induce a mutation in one of your skin cells that can transform the cell into a cancer cell. This is why long-term sun exposure can contribute to the development of skin cancer.
3. Chemical-induced mutations. Many chemicals, such as those found in cigarette smoke and in internal combustion engines, can also react with the atoms in DNA molecules and induce mutations.
1. Radiation
2. Chemical
3. Spontaneous 8

9. How does smoking/UV rays damage DNA?
1. Modify nucleotide bases

10. Phosphate backbone is broken

11. 2. Mistakes during DNA duplication (spontaneous mutation)

12. Nobel Prize in Chemistry 2015
Tomas Lindahl, Paul L. Modrich and Aziz Sancar were awarded the Nobel Prize in Chemistry for having mapped and explained how the cell repairs its DNA and safeguards its genetic information.

13. Chromosomal aberrations Gene deletion Gene relocation Gene duplication
Point mutations
1.Base insertion
2. Base deletion
3. Base substitution
Chromosomal aberrations
Gene deletion
Gene relocation
Gene duplication
Mutations generally fall into two types: point mutations and chromosomal aberrations. In point mutations, one base pair is changed, whereas in chromosomal aberrations, entire sections of a chromosome are altered.
Point mutations are mutations in which one nucleotide base pair in the DNA is replaced with another or in which a base pair is inserted or deleted. Insertions and deletions can be much more harmful than substitutions because they can alter the reading-frame for the rest of the gene. Remember that the amino acid sequence of a protein is determined by reading the bases on an mRNA molecule three at a time and attaching the specific amino acid that is specified by that sequence. If a single base is added or removed, the three-base groupings get thrown off and the sequence of amino acids stipulated will be all wrong. It’s almost like putting your hands on a computer keyboard, but offset by one key to the left or right, and then typing what should be a normal sentence. It comes out as gibberish.
Chromosomal aberrations are changes to the overall organization of the genes on a chromosome. Chromosomal aberrations are like the manipulation of large chunks of text within a paper. They can involve the complete deletion of an entire section of DNA, the moving of a gene from one part of a chromosome to another, or the duplication of a gene with the new copy inserted elsewhere on the chromosome. In any case, a gene’s expression—the production of the protein the gene’s sequence codes for—can be altered when it is moved, as can the expression of the genes around it. 13

14. Types of point mutations
Base substitution
Silent mutation: No change in amino acid sequence and so no new protein is formed
Sickle cell anemia: due to base substitution
Sometimes silent mutations

15. Base insertion
Base deletion

17. Frame shift
Reading frame shifts when there is base insertion or base deletions

18. Are mutations Harmful or Beneficial??
Depends on the particular gene mutation
Because they can change the protein produced, mutations can disrupt normal processes and harm the individual.
It turns out that many—perhaps even most—mutations are neutral, having neither a positive nor a negative effect on an organism’s phenotype. Based on a recent study, researchers estimate that the rate of germ line mutations is approximately 108 per base pair per generation.
A paradoxical fact about mutations is that they are essential to evolution. Those mutations that don’t kill an organism, or reduce its ability to survive and reproduce, can be beneficial. Every genetic feature in every organism was, initially, the result of a mutation. 18

19. Examples of favorable mutations Resistance to Atherosclerosis
Increased bone density
Mutations in a gene protects people from diabetes. They produce more insulin
Sickle cell resistance to malaria
HIV resistance
Orange color mutation leads to more nutritious cauliflower
Red heads more resistant to anesthetics!

20. Genetic mutation Basis of species diversity

21. Hereditary Mutation: either present in egg, sperm or the zygote

23. Natural protection against mutation
DNA proofreading
DNA repair
checking RNAs and proteins
4. Redundant Genetic code

24. Certain mutations are called “silent” because ___
A different protein is formed
No new protein is formed
A different amino acid sequence is formed
No new amino acid sequence is formed
E. Both B and D

25. What is the difference between normal and sickle cell hemoglobin at the primary level?
The linear sequence of amino acids are different
The shape of the protein is different
The coils and pleats of the protein are different
All of the above are different

26. Which mutation is germ-line (hereditary) mutation? Mutation A
Mutation B
Which mutation is germ-line (hereditary) mutation?
Mutation A
Mutation B

27. DNA Replication Relies on specific pairing of matching bases
One strand of DNA carries all the information needed to construct its complementary strand.

28. DNA Replication also known as DNA duplication:
Just before cells divide, the DNA molecule unwinds and each half of the unwound DNA molecule serves as the template for the new strand of DNA to be constructed by the enzyme DNA polymerase. AT the end of DNA replication there are two DNA molecules---each identical to the original DNA molecule.

30. duplicated
Unduplicated

31. DNA replication (DNA duplication)
Very rapid
Very accurate
Semiconservative

32. Semi conservative

33. Think about it….
In the bacteria E.coli the entire genome is replicated in just 40 minutes at a rate of 1000 nucleotides per second. In Eukaryotic cell the rate is 50 nucleotides per second. In which cell do you think there will be more mistakes?

34. What most likely happens if the DNA makes a mistake during replication and puts a C where a T should be?
It results in a mutation
The cell makes a new protein
The mistake is corrected
DNA replication stops

35. Mutations and Cancer

36. Number of New Cases per year
Chance of Surviving (%)
Pancreatic cancer Silent killer

37. Cancer Mutations in cell division/cell grwoth
Caused by multiple genetic mutations
Sometimes they are inherited cancers

38. Cancer related genes Proto-oncogenes when mutated become oncogenes
Tumor suppressor genes
DNA repair genes

39. Cologuard is an noninvasive colon cancer screening test based on stool sample
Colon cells in feces

40. Frequency of gene mutations in different types of cancer
Growth promoting gene called RAS is commonly mutated in cancer cells

41. Naked mole rat genome sequenced This is exciting news…Why?

42. One-gene, one-protein hypothesis
chromosome
gene
protein
Codes for

43. Tumor -Suppressor Genes (“brakes”)
Brakes failed!