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Tamarin: Principles of Genetics, Seventh Edition
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III. Molecular Genetics
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16. Gene Expression: Control in Eukaryotes
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The McGraw Hill Companies, 2001
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Gene Expression: Control in Eukaryotes
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PROBLEM 2: What stages in the formation of an immunoglobulin molecule generate diversity
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PROBLEM 3: How can you reconcile the viral and mutational natures of cancer
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Answer: Variability is generated through four general processes: choice of which subunit genes to combine, choice of how to combine these subunit genes, de novo generation of diversity at junctions, and unusually high mutation rates.Thus, in our description of the formation of a chain, diversity is added by (1) the choice of which variable and joining genes to combine; (2) recombinational variability at the point of recombination; (3) the creation of N segments at the junctions; and (4) somatic hypermutation.
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Answer: The two theories are reconciled because both de ne cancer as a disease caused by the inappropriate actions of genes. In the mutational view, inappropriate activity is generated by a gene mutation. In the viral view, a gene brought into the cell by a virus generates the inappropriate activity.
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E X E R C I S E S
CONTROL OF TRANSCRIPTION IN EUKARYOTES
A N D
P R O B L E M S*
1. Diagram the sequence on the yeast third chromosome as the mating type changes from a to and back again. 2. What are the differences between a general transcription factor and a speci c transcription factor 3. Tissue culture cells are exposed for ve minutes to radioactive dUTP in the presence or absence of 5-azacytidine. Radioactivity in RNA is determined to be 1,500 counts per minute without azacytidine and 27,300 in the presence of azacytidine. Propose an explanation to account for these results. 4. A retrovirus, lacking a cellular oncogene, is shown to be integrated 3 kilobases from a proto-oncogene. When the RNA for this oncogene is quanti ed, infected cells are found to have ten times more oncogene-speci c messenger RNA than uninfected cells. How can you account for this increase in RNA synthesis
PATTERNS IN DEVELOPMENT
10. What is meant by the statement that homeotic genes have been conserved evolutionarily 11. What are the four regions of the body plan of the developing Drosophila embryo laid out by maternaleffect genes What are the four major maternal-effect genes 12. What is a morphogen How does the Bicoid protein of Drosophila function as one 13. What is the helix-turn-helix motif of DNA binding What other motifs are known for DNA-binding proteins 14. If drugs that inhibit transcription are injected into fertilized eggs, early cell division and protein synthesis still occur. Why 15. Why do you suppose so much early research on developmental genetics was done with amphibians
CANCER
5. What is genomic equivalence, and why is explaining it a central problem in developmental genetics 6. What is the relationship between parasegments and segments in the developing Drosophila embryo 7. What are the three classes of segmentation genes in Drosophila embryos What are the effects of mutations of genes in each class 8. How does the hunchback gene function in Drosophila development 9. What are the differences between a syncitial and a cellular blastoderm in a Drosophila embryo
16. What gross chromosomal abnormalities are associated with cancers 17. From the pedigree of gure 16.26, what modes of inheritance would be consistent with each type of cancer, assuming that a single gene controlled each 18. What chromosomal abnormality is associated with retinoblastoma with Wilm s tumor 19. What is the proposed mechanism of action of the retinoblastoma gene What evidence supports this mechanism Why is it called an anti-oncogene 20. Retinoblastoma has been called a recessive oncogene. Explain. 21. What are the general forms of animal viruses What types of genetic material do they have 22. What is the minimal genetic complement of a retrovirus What does each of the genes code for
*Answers to selected exercises and problems are on page A-19.
Tamarin: Principles of Genetics, Seventh Edition
III. Molecular Genetics
16. Gene Expression: Control in Eukaryotes
The McGraw Hill Companies, 2001
Critical Thinking Questions
23. What translation mechanisms exist for the expression of the genes of a retrovirus 24. Assume that a particular oncogene produces a growth factor. a. How could a retrovirus affect the oncogene so that the cell becomes cancerous b. How could you test your hypothesis 25. What are the differences among v-src, c-src, and proto-src genes 26. How can the proto-src gene be activated 27. What is the evidence that the c-src gene came before the v-src gene 28. How does translocation activate the c-myc gene in Burkitt s lymphoma 29. A cDNA probe for a proto-oncogene is constructed. Cellular DNA from normal cells and a clone of cells infected with a retrovirus that lacks the oncogene (clone 1) is digested with a particular restriction enzyme. The DNA is separated in a gel and hybridized with the radioactive probe. The results appear in the following gure. Normal Clone 1
31. What components go into making an Ig light chain a heavy chain 32. How many different antibodies does a B lymphocyte produce How many can it potentially produce before it differentiates 33. What are the nucleotide recognition signals in V-J joining 34. What are B and T lymphocytes What roles do they play in the immune response 35. What is a T-cell receptor 36. What is the major histocompatibility complex 37. A disorder of the immune system is characterized by a complete lack of antibody production. Provide two possible molecular defects that would result in such a condition. 38. Many alleles for the genes for the constant region of antibodies have been found. Suppose that two such alleles for the light chain are called c1 and c2. In a heterozygote, c1c2, some cells are found to make only c1 and others only c2. Propose an explanation. 39. Complementary DNA is made from messenger RNA for the light chain of an antibody molecule. DNA from embryonic cells and from mature B lymphocytes is isolated and digested with a restriction enzyme, and the fragments are separated in a gel. Radioactive cDNA is used to probe this gel, and the results appear in the gure that follows. Provide an explanation for these results. Embryonic Lymphocytes
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