MUTATIONS

1. MUTATIONS

2. What is a Mutation? • A change in DNA • Mutations are NOT Teenage Mutant Ninja Turtles or XMen!!! • We are all mutants – products of the mutations in all of our ancestors before us

3. How Do Mutations Occur? • During DNA replication when bases are substituted, deleted, or added • During mitosis and/or meiosis when chromosomes don’t divide properly • During crossing over when chromatids “get lost” instead of being incorporated into its homolog’s DNA

4. Aging causes mutations when segments of DNA are degraded (telomeres) • Exposure to chemicals in the environment called mutagens (such as UV radiation, Xrays, some food dyes)

5. Somatic vs. Germ Cell Mutations • Somatic mutations affect cells of the body, such as skin, muscle, etc. • Somatic mutations can not be passed to offspring • Germ cells are cells that divide to make gametes • Germ cell mutations are passed to offspring

6. Example of Germ Cell Mutation • Queen Victoria had a germ cell mutation in cells that made her oocytes • The mutation was in a gene that makes a protein for blood to clot • She passed this mutation on to some of her children and they had hemophilia

9. Gamete cells mutations can result in genetic disorders. • If the parent survives with the disorder, it can be passed to another generation.

10. Example of Somatic Mutation • UV radiation from the sun can mutate DNA in skin cells and cause cancer • That cancer is not inherited

11. Gene vs. Chromosome Mutations • Gene mutations affect one gene and therefore one protein (or polypeptide) • Chromosome mutations affect a large part of a chromosome and all of the genes on that section of chromosome

12. Gene Mutations • Can occur during DNA replication • They are often point mutations, which affect a small number of bases or sometimes just one base pair

13. Types of Point Mutations • Insertion (Addition)–one (or a few) bases is (are) inserted • Deletion – one (or a few) base is (are) deleted • Substitution – one base is substituted with another one

15. Deletion and Insertion Mutations Can Cause a Frameshift

16. Sickle Cell

17. The mutation is in the gene for hemoglobin • Malformed hemoglobin molecules cause red blood cells to “sickle”

18. Red blood cells cause blood clots, which damage the kidneys and liver • Severity varies from person to person • Shortened life span (45 years is average) • Pain due to blood clots • Fatigue from lack of oxygen

21. Sickle Cell is Found in Certain Ancestral Groups

23. Sickle cell evolved as a protection against malaria • People with one sickle cell gene and one healthy gene don’t have sickle cell or get malaria!

24. Tay-Sachs • Children appear healthy at birth, but do not progress as other children • Child will stop smiling, sitting up, etc. • Blindness and eventually complete paralysis • Usually results in death by age 5

25. There is no cure • Mutation in a gene for an enzyme that processes lipids in the brain (Hex A) • The brain swells, crushing and killing parts of the brain • Mutation occurred in central and eastern Europe • Caused by a substitution mutation or a deletion mutation

28. Cystic Fibrosis • Deletion in a transport protein that allows Cl- to enter and exit cells • Causes thick mucus to build up in lungs, which causes repeated lung infections • Mucus clogs up pancreatic duct so food isn’t digested • Mucus causes intestinal blockage

29. Breathing treatments can loosen mucus in lungs to increase lung function and decrease chance of infection

30. Treated with antibiotics for infections • Use oral enzymes to digest food (increase in food intake to make up for undigested food) The mutation is found here  on chromosome 7

31. CF occurs in all ancestral backgrounds and is the most common fatal genetic disorder (about 1 in every 20 people carries the gene) • Severity of disease varies from person to person and they die from a respiratory infection or lung failure

33. Huntington’s • Named after Dr. George Huntington who first described it • Caused by an insertion mutation (CAG is repeated) Nancy Wexler

34. Causes jerky and uncontrolled movements • Slurred speech • Loss of memory • Symptoms progress and get worse with time; caused by degeneration of nerve cells • Symptoms usually appear between the ages of 35-40, but can be earlier

35. Found in all major ethic groups • Death is usually from pneumonia or choking • Can live 10-20 years after the onset of the symptoms; some die earlier

36. Albinism • Mutation in one of the genes for producing melanin which gives hair, skin, and eyes their color • Albinos often have vision defects

37. Nondisjunction Mutations (Type of Chromosome Mutation) • Occur when chromosomes fail to separate during meiosis • Results in a cell with an extra chromosome or a chromosome missing • The person wouldn’t have 46 chromosomes, but 45 or 47

38. An Example of a Nondisjunction MutationDown’s • Named after Dr. Down that first described it • Caused by 3 copies of the 21st chromosome (trisomy 21) • Causes heart defects, mental retardation, unclear speech, rounded face, almond shaped eyes, poor muscle tone, fold in the eyelid

39. Notice the 3 21st chromosomes

41. Another Example of NondisjunctionKlinefelter’s • An extra X chromosome (XXY) in males • Usually sterile, some have enlarged breasts, delayed learning, may be tall and thin, symptoms vary and may be undetectable

42. Notice the 3 sex chromosomes

43. How Klinefelter’s Occurs

44. And Another Example of NondisjunctionTurner’s • Have 1 X chromosome (XO) - females • About 98% of fetuses with Turner’s are spontaneously aborted (miscarried) • Short, swelling of hands and feet, sterile, and other symptoms vary from person to person