Exam 9: Genetic Approaches to Treating Disease

With regard to drug metabolism, which, if any, of the following statements, is true? a) The therapeutic window is simply the range of plasma drug concentrations in which the drug has therapeutic benefit. b) Each individual drug molecule is metabolized by a specific drug-metabolizing enzyme that is dedicated to the metabolism of that drug. c) An ultrafast metabolizer is a person who metabolizes a drug too quickly and so is at risk of an overdose d) A poor metabolizer is a person who cannot metabolize a drug properly and is at risk of an underdose.

Concerning stem cells, which of the following statements is incorrect?

Using the example of genes encoding cytochrome P450 enzymes, illustrate how genetic variation in drug-metabolizing enzymes can often stem from gene copy number variation.

Which, if any, of the following statements is false?

The CFTR gene that underlies cystic fibrosis was isolated by positional cloning in 1989. Twenty years later, Jack Riordan, one of the major contributors to this historic achievement, was quoted as saying "the disease has contributed much more to science than science has contributed to the disease". What did he mean by this, and what important developments have occurred in treating cystic fibrosis since 2009?

Which, if any, of the following statements is false?

Genome editing is being used in an attempt to cure HIV-AIDS. What is the experimental strategy towards achieving that goal?

Concerning the efficacy of small molecule drugs, which, if any, of the following statements is true?

What distinguishes phase I and phase II reactions in the metabolism of small molecule drugs?

Fill in the blanks with single words. In some diseases the problem is the loss of some function and a type of ____1_____ therapy is used to supplement the resulting deficiency. It may be a deficiency in some normal aspect of the ____2_____, such as deafness, a deficiency of organs or ____3____ , or a deficiency of molecules (which might be at the level of ____4_____ , ____5_____ , or downstream factors). Sometimes, however, disease is not due to a deficiency; instead, the problem is that there is some positively _____6_____ effect produced at some level (at the level of the phenotype, ____3_____ or ____4______ ), that cannot be supplemented. Here treatment is possible by seeking to eliminate, correct or ____ 7_____ the agent causing the positively _____6_____ effect. The treatment might seek to kill dangerous _____3____ , for example, or to ____7_____ a _____6_____ _____4_____ or a _____7_____ _____6_____. In the latter case, the treatment might often be to use some kind of _____8_____ , such as a conventional ____9_____ molecule ____8_____ that usually works by binding to a cleft in the _____6_____ _____5_____ and thereby ____7____ its ____6____ effect. A third class of disease treatment seeks to use a ____8____ in order to alter a person's ______10_______ to the disease, or to alter exposure to some _____11_____ factor.

Concerning gene transfer into human cells, which, if any, of the following statements is false?

Concerning animal models of human disease, which, if any, of the following statements is false?

Concerning transport of genes into human (or animal) cells, which, if any, of the following statements is false? a) Transduction means using viruses to transfer DNA into human (or other animal) cells. b) Tropism refers to the ability of certain viruses to transduce only certain types of cell, such as hepatocytes, but not neurons. c) Tropism depends on a virus being able to recognize a specific receptor molecule on the surface of the cell. d) Transfection means transferring DNA into the cells by any means other than using viruses.

There are three broad classes to disease treatment. Give a brief outline of the three classes.

Which of the following statements, if any, is false?

Which of the following descriptions, if any, is false? A person's ability to absorb or metabolize a drug that is intended to treat a genetic disorder

Which, if any, of the following statements is true? a) Autologous cell transplantation is involved in in vivo gene therapies: cells from an individual are genetically modified and then returned to that individual. b) Adenovirus vectors have the advantage that they offer very high level expression and are well suited to gene therapy for blood disorders. c) Adenovirus vectors have a better safety profile than adeno-associated virus vectors and have a larger insert size capacity. d) Adeno-associated virus vectors are well suited to gene therapy for blood disorders but have a low insert size capacity

The diagram below shows the urinary metabolic ratio as a measure of CYP2D6 enzyme activity in a total of about 700 individuals. After individuals were given a standard dose of a drug known to be metabolized by CYP2D6 the metabolic ratio was obtained by measuring the urinary concentration of the substrate drug and dividing it by the concentration of the metabolic product resulting from CYP2D6 acting on the drug. Classify individuals with metabolic ratios in the four ranges shown as (a) to (d) in terms of their drug-metabolizing abilities and describe the expected genotypes associated with each group.

What possible clinical applications might be derived from induced pluripotent stem cell technologies?

Hematopoietic stem cells can be important target cells in gene therapy for blood disorders and some other disorders, including certain brain disorders. Explain the significance of hematopoietic stem cells and how they are exploited in gene therapy.