Genetics: From Genes to Genomes
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 19P

Mouse models for human genetic diseases are potentially powerful tools to help geneticists understand the cause of the aberrant phenotypes and develop new therapeutic measures. However, such mice are not always as useful to investigators as it might seem at first glance. Suppose that you have a mouse knockout model for a human disease caused by homozygosity for a null allele of a gene. Discuss how the following situations might complicate investigations of the human disease based on this mouse model.

a. Mice have a shorter life span than humans.
b. Mice homozygous for certain knockout mutations die in utero.
c. Mouse genomes may have additional copies of the gene whose mutation causes the disease in humans.
d. Mice from different inbred lines homozygous for the same gene knockout vary in the penetrance and expressivity of the phenotype.
e. Manipulations to create the knockout mouse, such as the presence of a drug resistance gene that allows the selection of cells containing the knockout (see Fig. 18.9), can disrupt not only the targeted gene, but also the expression of other, nearby genes.
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Mouse models for human genetic diseases are potentially powerful tools to help geneticists understand thecause of the aberrant phenotypes and develop newtherapeutic measures. However, such mice are not always as useful to investigators as it might seem at firstglance. Suppose that you have a mouse knockoutmodel for a human disease caused by homozygosityfor a null allele of a gene. Discuss how the followingsituations might complicate investigations of the human disease based on this mouse model.a. Mice have a shorter life span than humans.b. Mice homozygous for certain knockout mutationsdie in utero.c. Mouse genomes may have additional copies of thegene whose mutation causes the disease in humans.d. Mice from different inbred lines homozygous forthe same gene knockout vary in the penetrance andexpressivity of the phenotype.e. Manipulations to create the knockout mouse, suchas the presence of a drug resistance gene that allowsthe selection of cells containing the knockout (seeFig. 18.9),…
The ability to selectively modify the genome in the mouse has revolutionized mouse genetics. Outline the procedure for generating a knockout mouse at a specific genetic locus. How can the loxP-Cre system be used to conditionally knock out a gene? What is an important medical application of knockout mice?
Two approaches for correcting single-gene defects are gene therapy such as is discussed in Section 3-5D and the CRISPR–Cas9 system. Explain why the CRISPR–Cas9 approach can potentially provide more complete restoration of normal tissue function than gene therapy.

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Genetics: From Genes to Genomes

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Mitochondrial mutations; Author: Useful Genetics;https://www.youtube.com/watch?v=GvgXe-3RJeU;License: CC-BY