Biology 234 J. G. Doheny Chapter 16 Mutations Practice Questions: Answer the following questions with one or two sentences. 1. List the name of one test that can be used to identify mutagens. 2. What is the general term for a mutation that only changes one base pair in a coding sequence? 3. What do you call a mutation to a gene that changes a single base pair, but which has no effect on the amino acid sequence? 4. What do you call a mutation that changes a single purine for another purine? 5. What do you call a mutation that changes a single purine for a pyrimidine? 6. What do you call a mutation that changes a single base pair in a gene, and which has the effect of changing one amino acid in the protein for another amino acid with SIMILAR biochemical properties? 7. What do you call a mutation that changes a single base pair in a gene, and which has the effect of changing one amino acid for another amino acid with DIFFERENT biochemical properties? 8. What do you call a mutation to a gene that changes a coding codon into a STOP codon? 9. What do you call a mutation where a chromosome is broken in two places, inverted 180 and then ligated back together? What is the general term for this type of mutation? What would you call it if the inverted segment included the centromere? What would you call it if it DID NOT include the centromere? 10. List one specific example of a paracentric inversion. (Hint: you learned about it when you studied PEV!) 11. In chromosome shorthand, how would you denote a reciprocal translocation between chromosomes 9 and 22? 12. What do you call a mutation where there is absolutely no gene product? 13. What type of mutation would be generated if the PROMOTER of a gene were mutated in such a way that absolutely no mrna would be produced? 14. What would you call a mutation where a gene that encodes an enzyme is mutated such that the enzyme still does what it s supposed to do, but only half as fast? 15. What would you call a mutation where a gene that encodes an enzyme is mutated such that the enzyme would still do what it s supposed to do, but twice as fast as it normally would? 16. List the names of two TRE genetic disorders. 17. List the names of one genetic disorder that involves a mutation to the DNA proofreading and repair enzymes. 1
18. List one example of a genetic disease that involves a mutation to a tumor suppressor mutation. 19. List one form of cancer that involves a chromosome translocation. 20. What does CML stand for? (Hint: It s a form of cancer caused by a reciprocal translocation.) 21. Are oncogenes generally gain of function mutations or loss of function 22. Are tumor suppressor genes generally gain of function mutations or loss of function 23. MUTAGENS: Which mutagen would you use to deliberately induce POINT 24. MUTAGENS: Which mutagen would you use to deliberately induce FRAMESHIFT 25. MUTAGENS: Which mutagen would you use to deliberately induce chromosome rearrangements? 26. MUTAGENS: Which mutagen would you use to (hopefully) induce a reversion mutation of a point mutation? 27. MUTAGENS: Which mutagen would you use to (hopefully) induce a reversion mutation of a frameshift mutation? 28. MUTAGENS: Which mutagen would you use to (hopefully) induce a reversion mutation of a paracentric inversion? 29. MUTAGENS: Which mutagen would you use to (hopefully) induce a reversion mutation of a translocation? 30. Yes or no: can you generate a somewhat normal reversion mutation to a frameshift by inducing a second frameshift? 31. Yes or no: can you generate a reversion mutation to a deletion by causing another deletion? 32. What does the genetic shorthand t(9;22) stand for? 33. What does the genetic shorthand t(8;14) stand for? Be able to answer the following questions in one or two paragraphs: 1. List at least two changes to a chromosome that will generate a NULL mutation? 2. What is a point mutation? 3. What is a translocation mutation? 4. What is a hypomorphic mutation? 5. What is a hypermorphic mutation? 6. What is a null mutation? 7. What is an INDEL mutation? 8. What is a dominant negative mutation? 9. What is an antimorphic mutation? 10. What is a hemizygote? 11. What is an inversion mutation? 12. What is a paracentric inversion? 13. What is a pericentric inversion? 14. What is the difference between a paracentric and a pericentric inversion? 15. What is a deletion mutation? 2
16. What is a duplication mutation? 17. What is a dynamic mutation? 18. What is a TRE mutation? 19. What is a reversion mutation? 20. What is a suppressor mutation? 21. What is a transition mutation? 22. What is a transversion mutation? 23. What is a synonymous mutation? 24. What is a conservative missense mutation? 25. What is a nonconservative missense mutation? 26. What is a nonsense mutation? 27. What is a frameshift mutation? 28. What is a thymine dimer? 29. What is a loss of function mutation? 30. What is a gain of function mutation? 31. What is an intercalating agent, and what does it do? Give an example of an intercalating agent. (Hint: what is intercalation?) 32. What is intercalation? 33. Explain how a point mutation to an intron splice site can have a dramatic effect on the protein encoded, and change many amino acids. 34. Explain how you could cause a reversion mutation to a frameshift mutation by causing further frameshift mutations. (ie-how would causing a second frameshift mutation fix the original mutation?) 35. Explain how you could fix a small frameshift mutation by inducing a small deletion mutation. 36. The genetic chromosome shorthand t(9;22) refers to something that happened to create the Philadelphia Chromosome, which is the cause of Chronic Myeloid Leukemia. Please explain what this shorthand means. 37. What is the nature of the Philadelphia Chromosome mutation? 38. Referring to cancer: what is METASTASIS? Be able to explain the following in one hand-written page or less: 1. Phenotypically, reversion mutations and suppressor mutations look the same, but they are not actually the same. What is the difference between a reversion mutation and a suppressor mutation? 2. What is the Ames Test for mutagens? Explain what it is used for, and how it works. 3. Does the Ames Test for mutagens have any BIAS in favor of specific types of mutagens? If so, which mutagens does the Ames Test preferentially screen for, and why? 4. When discussing a specific gene, what is the difference between a homozygote, a heterozygote, and a hemizygote? 5. When discussing mutations to a specific gene, what is the difference between a null, a hypomorph, a hypermorph, and an antimorph? 6. When discussing point mutations, what is the difference between a conservative missense mutation, and a nonconservative missense mutation? 7. What is an Oncogene? 3
8. What is a Tumor Suppressor gene? 9. What is the difference between a regular translocation and a reciprocal translocation? 10. What is the difference between an Oncogene and a Tumor Suppressor gene? (Include some of the characteristics of each.) 11. What is the difference between a gain of function mutation and a loss of function mutation? 12. When discussing point mutations, what is the difference between a synonymous mutation, a conservative missense mutation, a nonconservative missense mutation, and a nonsense mutation? 13. Most cancers spontaneously appear in people who have no history of cancer in their family. However, some unfortunate individuals are born with a predisposition to cancer. Explain how this happens, and list one example of how it happens. HUMAN GENETIC DISORDERS: Be able to explain a few things about how the following genetic diseases work: 1. Achondroplasia: Dwarfism. Autosomal dominant, single gene disorder. The mutated gene is the FGFR3 gene (Fibroblast Growth Factor 3 Gene) on Chromosome 4. It is a dominant negative mutation. It is homozygous lethal. Dwarfs have one mutant copy, and one Wild-Type copy of the gene. This is an example of an autosomal dominant genetic disorder. (Almost all dominant genetic diseases are homozygous lethal.) 2. Huntington s Disease: Autosomal dominant, single-gene disorder caused by a dynamic mutation. It is a dominant negative mutation to the HTT gene on Chromosome 4, which encodes the Huntingtin protein. It is homozygous lethal. It causes dementia in middle age. It is a PolyQ (TRE) genetic disease caused by dynamic mutation. It displays anticipation. This is an example of an autosomal dominant genetic disorder that is caused by a dynamic mutation. 3. Fragile X Syndrome: X-linked recessive, single-gene disorder caused by a dynamic mutation. It is caused by a RECESSIVE mutation to the FMR1 gene on the X chromosome. It causes mental retardation. Because it is recessive, and is carried on the X chromosome, it is much more common in boys than girls. (It is an X-linked, rather than an autosomal genetic disorder.) It is caused by a dynamic mutation (TRE) between the gene FMR1 gene and its promoter. This is an example of a recessive, X-Linked genetic disorder that is caused by a dynamic mutation. 4. Chronic Myeloid Leukemia: Autosomal dominant, single gene (oncogene), gain of function mutation caused by a translocation. A dominant, gain of function mutation that causes leukemia by placing a cell division gene (ABL1) that is normally turned off, under the control of an antibody promoter that is normally turned on in leukocytes (the BCR gene). This is caused by a t(9;22) reciprocal translocation that is called the Philadelphia Chromosome. The ABL1 gene is a proto-oncogene, and the translocation causes a dominant, gain of function mutation, converting it to an oncogene. 4
5. Burkitt s Lymphoma: t(8;14) Autosomal dominant, single gene, gain of function mutation caused by a translocation. A dominant, gain of function mutation that causes lymphoma by placing a cell division gene (Myc), which is normally turned off, under the control of an antibody gene promoter that is often turned on in lymphocytes. The Myc gene is a proto-oncogene, and the translocation causes a dominant, gain of function mutation, converting it to an oncogene. 6. Xeroderma Pigmentosum (XP): Autosomal recessive, multi-gene disorder. A recessive genetic disorder caused by mutations to any of several genes that encode proteins involved in the Nucleotide-Excision Repair complex (NER). The complex finds and removes fused pyrimidines ( thymine dimers ) and replaces them. If the NER complex is not functioning properly, skin cancers are common due to UV radiation fusing pyrimidines, and causing genetic mutations in skin cells that are not repaired by the NER complex. Such people must stay out of sunlight. 7. Phenylketonuria (PKU): Autosomal recessive, single gene disorder. Caused by a mutation to the Phenylalanine Hydrolase gene (PAH gene) located on Chromosome 12. When people with PKU eat protein, they do not have to ability to get rid of a toxic waste product that results from the breakdown of the amino acid phenylalanine. Therefore, they must eat a special diet. 8. Retinoblastoma (RB): Autosomal recessive, loss of function mutation to the RB1 gene on Chromosome 13. The RB1 protein is a DNA repair enzyme that is expressed in the retina of the eye. Some unfortunate people are born with one copy that is already mutated, and if the other copy becomes mutated in ANY ONE of the cells that make up the retinas of their eyes during their lifetime, they will almost certainly develop retinoblastoma (cancer of the retina) and have to have the effected eye removed. 9. Hemophilia: An X-linked, recessive disorder caused by mutations to one of two proteins involved in blood clotting (either Factor VIII or Factor IX). More common in men than women because women have two X chromosomes. People with hemophilia have trouble with blood clotting. (Blood takes longer to clot, wounds take longer to heal etc.) 5