Concepts of Genetics (12th Edition)
12th Edition
ISBN: 9780134604718
Author: William S. Klug, Michael R. Cummings, Charlotte A. Spencer, Michael A. Palladino, Darrell Killian
Publisher: PEARSON
expand_more
expand_more
format_list_bulleted
Videos
Textbook Question
Chapter 24, Problem 28ESP
The table in this problem summarizes some of the data that have been collected on mutations in the BRCA1 tumor-suppressor gene in families with a high incidence of both early-onset breast cancer and ovarian cancer.
Predisposing Mutations in BRCA1
*NA indicates not applicable, as the regulatory mutation is inferred and the position has not been identified.
- (a) Note the coding effect of the mutation found in kindred group 2082. This results from a single base-pair substitution. Draw the normal double-stranded DNA sequence for this codon (with the 5′ and 3′ ends labeled), and show the sequence of events that generated this mutation, assuming that it resulted from an uncorrected mismatch event during
DNA replication. - (b) Examine the types of mutations that are listed in the table, and determine if the BRCA1 gene is likely to be a tumor-suppressor gene or an oncogene.
- (c) Although the mutations listed in the table are clearly deleterious and cause breast cancer in women at very young ages, each of the kindred groups had at least one woman who carried the mutation but lived until age 80 without developing cancer. Name at least two different mechanisms (or variables) that could underlie variation in the expression of a mutant
phenotype , and propose an explanation for the incomplete penetrance of this mutation. How do these mechanisms or variables relate to this explanation?
Expert Solution & Answer
Want to see the full answer?
Check out a sample textbook solution
Students have asked these similar questions
Below are data from Jimenez et al (2022) depicting cellular expression patterns of the tumor suppressor transcription factor p53 (a gene commonly mutated in cancers). They explored oscillating expression patterns found in a mutated human cell line. Panel D shows measurements of changes in p53 mRNA levels measured using two different approaches; figure E shows measurements of protein levels from the same samples. The numbers on either side indicate the observed fold change (FC) in relative abundance of these molecules (note that any difference in values obtained between the two methods are not relevant for this question).
Answer part b as pictured in the question
Briefly describe how mitotic recombination can result in loss of heterozygosity (LOH) at tumor
suppressor gene loci.
mice were treated with a virus that inhibited expression of angiopoietin 2, MMP3 and MMP10 in the lung or with a control virus (Mock). Breast cancer cells that express the gene luciferase were then injected into the mammary glands of the mice. The metstasis of the tumors to the lungs could then be measured by imaging the presence of luciferase in the lungs. In 5-6 sentences, explain the data below and why knockout of Angpt2, MMP3 and MMP10 appears to inhibit metstastasis.
Chapter 24 Solutions
Concepts of Genetics (12th Edition)
Ch. 24 - Prob. 1NSTCh. 24 - People with a genetic condition known as...Ch. 24 - Prob. 3NSTCh. 24 - Cancer can arise spontaneously, but it can also be...Ch. 24 - Prob. 1CSCh. 24 - Prob. 2CSCh. 24 - If you agree to participate and then learn that...Ch. 24 - HOW DO WE KNOW? In this chapter, we focused on...Ch. 24 - Prob. 2PDQCh. 24 - Where are the major regulatory points in the cell...
Ch. 24 - List the functions of kinases and cyclins, and...Ch. 24 - How can mutations in noncoding segments of DNA...Ch. 24 - What is the difference between saying that cancer...Ch. 24 - Prob. 7PDQCh. 24 - Prob. 8PDQCh. 24 - Define tumor-suppressor genes. Why is a mutated...Ch. 24 - Describe the steps by which the TP53 gene responds...Ch. 24 - Part of the Ras protein is associated with the...Ch. 24 - Prob. 12PDQCh. 24 - Distinguish between oncogenes and proto-oncogenes....Ch. 24 - Prob. 14PDQCh. 24 - How do translocations such as the Philadelphia...Ch. 24 - Explain why many oncogenic viruses contain genes...Ch. 24 - Prob. 17PDQCh. 24 - How do normal cells protect themselves from...Ch. 24 - Prob. 19PDQCh. 24 - Epigenetics is a relatively new area of genetics...Ch. 24 - Radiotherapy (treatment with ionizing radiation)...Ch. 24 - Genetic tests that detect mutations in the BRCA1...Ch. 24 - Explain the apparent paradox that both...Ch. 24 - As part of a cancer research project, you have...Ch. 24 - Mutations in tumor-suppressor genes are associated...Ch. 24 - Prob. 26ESPCh. 24 - Those who inherit a mutant allele of the RB1...Ch. 24 - The table in this problem summarizes some of the...Ch. 24 - Researchers have identified some tumors that have...Ch. 24 - Prob. 30ESP
Knowledge Booster
Learn more about
Need a deep-dive on the concept behind this application? Look no further. Learn more about this topic, biology and related others by exploring similar questions and additional content below.Similar questions
- Loss of p53 function occurs in the majority of human tumors. Name two ways in which loss of p53 function contributes to a malignant phenotype. Explain how benzo(a) pyrene can cause loss of p53 function.arrow_forwardTumor-suppressor genes are normal human genes that prevent uncontrollable cell growth. Starting with a normal laboratory humancell line, describe how you could use transposon tagging to identifytumor-suppressor genes. (Note: When a TE hops into a tumorsuppressorgene, it may cause uncontrolled cell growth. This is detected as a large clump of cells among a normal monolayer of cells.)arrow_forwardCD3 is a signaling protein that is typically found only in the plasma membrane of immune system T lymphocytes. CD3 is composed of several different polypeptides, including a gamma chain, CD3γ. Scientists analyzed the promoter of the CD3γ chain gene for regulatory sequences that might have positive or negative effects on expression of the gene. The scientists cloned fragments of the CD3γ gene that included the first transcribed nucleotides plus up to 789 nucleotides of upstream regulatory sequences into plasmids in which the gene for the firefly enzyme luciferase immediately follows the fragments. The plasmids were then introduced into a line of T lymphocytes (Figure 1), and the cells were allowed to grow for a short while. Because the regulatory sequences of the CD3γ gene immediately precede the luciferase gene in the plasmids, the activity, either positive or negative, of the regulatory sequences affected the amount of luciferase gene expression by the T lymphocytes. Luciferase…arrow_forward
- Below is a figure (here called Figure 1) from “Prognostic Significance of CpG Island Methylator Phenotype and Microsatellite Instability in Gastric Carcinoma,” by An et al., published in Clinical Cancer Research in 2005. The authors look at five microsatellite loci (BAT 25, BAT 26, D2S123, D5S346, and D17S250) in normal (N) and tumor (T) tissue from patients with Gastric Carcinoma. They amplify the loci by PCR and then instead of using standard agarose gel electrophoresis, they run the PCR products through capillary gel electrophoresis and detect bands as they pass a laser near the positive charge terminal. The x-axis in these plots is the time at which the band passed the laser (aka size of the PCR product) and the intensity of the peaks represents the amount of DNA in that band A. Which patient- 18, 30, or 1- shows the most microsatellite instability? Which patient shows the least? How do you know? B. In which repair pathway is it most likely that you will find the driver mutations…arrow_forwardMutational signatures of p53 are shown in this image (G.P. Pfeifer et al., Nature, 21(48), 2002) for the three types of cancer with the highest death rates in the United States: lung (~225,000 deaths in 2016), breast (246,000), and colorectal (381,000). These data can be obtained by sequencing the gene that encodes p53. Approximately 85 percent of lung cancers occur in smokers. Based on these data, calculate how many deaths due to lung cancer among nonsmokers were reported in 2016. How much does smoking increase the likelihood of death due to lung cancer?arrow_forwardCellular levels of tumor suppressor protein p53 is maintained by a ubiquitin ligase protein, called Mdm2. Over expression of Mdm2 destabilizes p53. Another protein p19ARF inhibits the activity of Mdm2, thus stabilizing p53. Loss of p19ARF function converts normal cells into cancer cells With the above information, which of the following statements are true? Mdm2 is a tumor suppressor gene but p19ARF is an oncogene Both Mdm2 & P19ARF are oncogenes Both Mdm2 & P19ARF are tumor suppressor genes O Mdm2 is an oncogene but p19ARF is a tumor suppressor genearrow_forward
- Describe the common signal transduction event that is perturbed by cancer-promoting mutations in the genes encoding RAS and NF-1. Why are mutations in RAS more commonly found in cancers than mutations in NF-1?arrow_forwardResearchers have identified some tumors that have no recurrent mutations or deletions in known oncogenes or tumor-suppressor genes and no detectable epigenetic alterations. However, these tumors often have large chromosomal deletions. What are some possible explanations that could account for the genetic causes behind these tumors?arrow_forwardGenetic tests that detect mutations in the BRCA1 and BRCA2 tumor-suppressor genes are widely available. These tests reveal a number of mutations in these genes—mutations that have been linked to familial breast cancer. Assume that a young woman in a suspected breast cancer family takes the BRCA1 and BRCA2 genetic tests and receives negative results. That is, she does not test positive for the mutant alleles of BRCA1 or BRCA2. Can she consider herself free of risk for breast cancer?arrow_forward
- The p53 protein was discovered through its association with SV40 T antigen and assumed initially to be an oncoprotein. a. What is the current consensus as the function of p53 and what evidence caused this change in view? b. How does the effect of mutation in the p53 gene differ from the effect of mutation in the RB gene what is the molecular basis for this difference ?arrow_forwardDescribe error prone polymerases and the process of translesion synthesis (TLS). In regards to tumor biology, what is the mutator phenotype hypothesis? What are some ways in which error-prone polymerases could be targeted for potential anti-cancer treatments?arrow_forwardDescribe the various post-translational modifications of HIF- 1alpha and how it affects the regulation of HIF-1al pha signaling. How might HIF- alpha alter the tumor microenvironment to promote tumor growth? Propose a strategy to prevent HIF-alpha signaling in the TME. What do you think would happen in a transgenic mouse with a total knockout of HIF-alpha?arrow_forward
arrow_back_ios
SEE MORE QUESTIONS
arrow_forward_ios
Recommended textbooks for you
Human Anatomy & Physiology (11th Edition)BiologyISBN:9780134580999Author:Elaine N. Marieb, Katja N. HoehnPublisher:PEARSON
Biology 2eBiologyISBN:9781947172517Author:Matthew Douglas, Jung Choi, Mary Ann ClarkPublisher:OpenStax
Anatomy & PhysiologyBiologyISBN:9781259398629Author:McKinley, Michael P., O'loughlin, Valerie Dean, Bidle, Theresa StouterPublisher:Mcgraw Hill Education,
Molecular Biology of the Cell (Sixth Edition)BiologyISBN:9780815344322Author:Bruce Alberts, Alexander D. Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter WalterPublisher:W. W. Norton & Company
Laboratory Manual For Human Anatomy & PhysiologyBiologyISBN:9781260159363Author:Martin, Terry R., Prentice-craver, CynthiaPublisher:McGraw-Hill Publishing Co.
Inquiry Into Life (16th Edition)BiologyISBN:9781260231700Author:Sylvia S. Mader, Michael WindelspechtPublisher:McGraw Hill Education
Human Anatomy & Physiology (11th Edition)
Biology
ISBN:9780134580999
Author:Elaine N. Marieb, Katja N. Hoehn
Publisher:PEARSON
Biology 2e
Biology
ISBN:9781947172517
Author:Matthew Douglas, Jung Choi, Mary Ann Clark
Publisher:OpenStax
Anatomy & Physiology
Biology
ISBN:9781259398629
Author:McKinley, Michael P., O'loughlin, Valerie Dean, Bidle, Theresa Stouter
Publisher:Mcgraw Hill Education,
Molecular Biology of the Cell (Sixth Edition)
Biology
ISBN:9780815344322
Author:Bruce Alberts, Alexander D. Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter
Publisher:W. W. Norton & Company
Laboratory Manual For Human Anatomy & Physiology
Biology
ISBN:9781260159363
Author:Martin, Terry R., Prentice-craver, Cynthia
Publisher:McGraw-Hill Publishing Co.
Inquiry Into Life (16th Edition)
Biology
ISBN:9781260231700
Author:Sylvia S. Mader, Michael Windelspecht
Publisher:McGraw Hill Education
What are Mutations and what are the different types of Mutations?; Author: Science ABC;https://www.youtube.com/watch?v=I16YlE8qTBU;License: Standard youtube license