Sanders 3rd Edition
Ch. 14 - Analysis of Gene Function via Forward Genetics and Reverse GeneticsProblem 1
What are the advantages and disadvantages of using GFP versus lacZ as a reporter gene in mice, C. elegans, and Drosophila?
Problem C.1d
Identify the normal functions of the following genes whose mutations are associated with the development of cancer.
APC (familial adenomatous polyposis)
Problem C.1a
Identify the normal functions of the following genes whose mutations are associated with the development of cancer.
RB1 (retinoblastoma)
Problem C.1c
Identify the normal functions of the following genes whose mutations are associated with the development of cancer.
p53 (Li–Fraumeni syndrome)
Problem C.1e
Identify the normal functions of the following genes whose mutations are associated with the development of cancer.
Which of these genes would you classify as a proto-oncogene and which as a tumor suppressor gene? Explain your categorization for each gene.
Problem C.1b
Identify the normal functions of the following genes whose mutations are associated with the development of cancer.
c-MYC (Burkitt lymphoma)
Problem 2
You conduct a study in which the transcriptional fusion of regulatory sequences of a particular gene with a reporter gene results in relatively uniform expression of the reporter gene in all cells of an organism. A translational fusion with the same gene shows reporter gene expression only in the nucleus of a specific cell type. Discuss some biological causes for the difference in expression patterns of the two transgenes.
Problem C.2b
A tumor is a growing mass of abnormal cells. Give an example from this chapter of a benign tumor that becomes a malignant tumor.
Problem C.2a
A tumor is a growing mass of abnormal cells. Describe the difference between a benign tumor and a malignant tumor.
Problem C.2c
A tumor is a growing mass of abnormal cells. What must happen for a benign tumor to become malignant?
Problem 3
Discuss the similarities and differences between forward and reverse genetic approaches, and when you would choose to utilize each of the approaches.
Problem B.3
Go to the National Institute for Child Health and Human Development (http://www.nichd.nih.gov), locate the search box at the top right corner of the homepage, and enter 'RUSP' to search for information on the Recommended Uniform Screening Panel. From the options that appear, select 'Brief History of Newborn Screening' and locate the discussion listing the criteria for adding a disease to the RUSP list. What are the criteria for listing a disease on the RUSP list?
Problem C.3b
For the retinal cancer retinoblastoma, the inheritance of one mutated copy of RB1 from one of the parents is often referred to as a mutation that produces a 'dominant predisposition to cancer.' This means that the first mutation does not produce cancer but makes it very likely that cancer will develop.
Explain why cancer is almost certain to develop with the inheritance of one mutated copy of RB1.
Problem 4
Using the data in Table B, calculate the average number of kilobase (kb) pairs per centimorgan in the six multicellular eukaryotic organisms. How would this information influence strategies to clone genes known only by a mutant phenotype in these organisms?
Problem B.4
What are community-based genetic screening programs? What is the intent of such screening programs? Why are members of specific communities or populations offered the chance to participate in such programs?
Problem C.4b
Explain the following processes involving chromosome mutations and cancer development.
How the chromosome mutation producing Burkitt lymphoma generates the disease.
Problem C.4a
Explain the following processes involving chromosome mutations and cancer development.
How the chromosome mutation producing the Philadelphia chromosome leads to CML.
Problem 5
What are the advantages and disadvantages of using insertion alleles versus alleles generated by chemicals (as in TILLING) in reverse genetic studies?
Problem 6
You have cloned the mouse ortholog of the gene associated with human Huntington disease (HD) and wish to examine its expression in mice. Outline the approaches you might take to examine the temporal and spatial expression pattern at the cellular level.
Problem C.6a
Radiation is frequently used as part of the treatment of cancer. The radiation works by damaging DNA and components of the cell. How can radiation treatment control or cure cancer?
Problem C.6c
Radiation is frequently used as part of the treatment of cancer. The radiation works by damaging DNA and components of the cell. Under what circumstances do you think radiation treatment is a good choice to treat cancer?
Problem C.6b
Radiation is frequently used as part of the treatment of cancer. The radiation works by damaging DNA and components of the cell. Is there a risk of damage to noncancer cells?
Problem 7
Diagram the mechanism by which CRISPR–Cas functions in the immune system of bacteria and archaea.
Problem C.7b
Why do most cancers require the mutation of multiple genes?
Problem C.7c
Based on what you read in this chapter, Can a tumor arise from a single mutated cell? Are all the cells in a tumor identical?
Problem 8
Describe how CRISPR–Cas has been modified to create a genome-editing tool.
Problem B.8
Do you think it is important that participation in community-based genetic screening be entirely voluntary? Why or why not?
Problem C.8a
The inheritance of certain mutations of BRCA1 can make it much more likely that a woman will develop breast or ovarian cancer in her lifetime. Can you say with certainty that a woman inheriting a mutation of BRCA1 will definitely develop breast or ovarian cancer in her lifetime? Why or why not?
Problem C.8b
The inheritance of certain mutations of BRCA1 can make it much more likely that a woman will develop breast or ovarian cancer in her lifetime. In addition to inheriting a BRCA1 mutation, what else must happen for a woman to develop breast or ovarian cancer?
Problem 9
Discuss the advantages (and possible disadvantages) of the different approaches to reverse genetics.