Genetics: From Genes to Genomes
6th Edition
ISBN: 9781259700903
Author: Leland Hartwell Dr., Michael L. Goldberg Professor Dr., Janice Fischer, Leroy Hood Dr.
Publisher: McGraw-Hill Education
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Chapter 18, Problem 34P
One potential strategy for gene therapy to correct the effects of dominant gain-of-function mutations is to express small interfering RNAs (siRNAs) that will cause degradation of mRNA produced by the dominant mutant allele. The siRNAs can be delivered to patient cells by a synthetic gene encoding a hairpin RNA that will be processed by Dicer and used to target the RISC complex to the mutant allele mRNA (review Figs. 17.32 and 17.33).
a. | A major problem with this gene therapy strategy is designing an siRNA that will prevent the expression of the mutant allele specifically and not the normal allele. Explain why this is a problem. |
b. | Specificity for the mutant allele is a particular problem in designing an siRNA therapy gene for Huntington disease. Explain this issue and suggest a possible solution that would allow you to use RNAi. |
c. | Another potential strategy to correct the mutant Huntington disease allele is to cut the DNA in the middle of the repeat tract. Exonucleases present in the nucleus would then degrade many of the repeats prior to repair by NHEJ. Could you use CRISPR/Cas9 technology to correct Huntington disease mutations with this approach? (Hint: See Problems 28 and 29.) |
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A gene encodes a protein with the following amino acid sequence: Met-Lys-Ser-Pro-Ala-Thr-Pro A nonsense mutation caused by a single-base-pair substitution occurs in this gene, resulting in a protein with the amino acid sequence Met-Lys. An intergenic suppressor mutation allows the gene to produce the fulllength protein. With the original mutation and the intergenic suppressor present, the gene now produces a protein with the following amino acid sequence: Met-Lys-Cys-Pro-Ala-Thr-Pro Give the location and nature of the original mutation and of the intergenic suppressor.
Mice usually have wild-type agouti fur that appears grey, but a mouse geneticist has a pure-breeding white-furred strain that is homozygous for a recessive mutation. Molecular analysis shows that the mutation is a missense mutation in an exon common to three alternatively spliced forms of a gene expressed in hair follicles. Which of the following transgenic animals would be most useful to determine which spliced form (or forms) is sufficient to specify agouti fur?A. Construct a GFP reporter using the promoter for the identified gene.
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C. Use CRISPR/Cas9 to make a large deletion of the entire coding region of the identified gene.
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Chapter 18 Solutions
Genetics: From Genes to Genomes
Ch. 18 - Match each of the terms in the left column to the...Ch. 18 - Mice are usually gray, but a mouse geneticist has...Ch. 18 - Sometimes, genes transferred into the mouse genome...Ch. 18 - In mice, a group of so-called Hox genes encode...Ch. 18 - The fly eyes shown in Fig. 18.7 are malformed...Ch. 18 - This problem concerns a technique called enhancer...Ch. 18 - Fish and other organisms that live in the Arctic...Ch. 18 - a. Describe two ways you could potentially make a...Ch. 18 - Figure 18.6 shows a picture of Glofish ,...Ch. 18 - Some people are concerned about the possible...
Ch. 18 - The goal of the Knockout Mouse Project is to...Ch. 18 - Prob. 12PCh. 18 - Prob. 13PCh. 18 - a. Which genome manipulation technique would you...Ch. 18 - a. Diagram a knockin construct that could have...Ch. 18 - Prob. 16PCh. 18 - Prob. 17PCh. 18 - The transcription factor Pax6 is required...Ch. 18 - Mouse models for human genetic diseases are...Ch. 18 - One way to determine where inside a cell a protein...Ch. 18 - In Problem 5 in Chapter 17, you saw that a SNP...Ch. 18 - Scientists now routinely use CRISPR/Cas9 to make...Ch. 18 - Geneticists are currently considering using...Ch. 18 - a. Figures 18.9 and 18.12 demonstrated methods to...Ch. 18 - Nonhomologous end-joining NHEJ of a double-strand...Ch. 18 - One problem that researchers sometimes encounter...Ch. 18 - Researchers at the University of California at San...Ch. 18 - Prob. 28PCh. 18 - F. Port and S. Bullock at the University of...Ch. 18 - On Fig 18.14, locate the PAM site and identify the...Ch. 18 - Prob. 31PCh. 18 - Prob. 32PCh. 18 - Recall that Leber congenital amaurosis LCA, a form...Ch. 18 - One potential strategy for gene therapy to correct...Ch. 18 - Recently, scientists have used a mouse model for...
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