recap

15.5 recap

Treatment of a human genetic disease may involve an attempt to modify the abnormal phenotype by restricting the substrate of a deficient enzyme, inhibiting a harmful metabolic reaction, or supplying a missing protein. By contrast, gene therapy aims to address a genetic defect by inserting a normal allele into a patient’s cells.

learning outcomes

You should be able to:

  • Explain how a genetic disease can be treated by modifying the disease phenotype.

  • Compare ex vivo and in vivo approaches to gene therapy.

Question 1

How do metabolic inhibitors function in treating genetic diseases such as cancer?

Metabolic inhibitors block important chemical transformations in cancer cells. An inhibitor may either block the accumulation of a harmful substance or block cancer-specific transformations to harmful substances.

Question 2

How does in vivo gene therapy work? Can you give an example?

In vivo gene therapy inserts the wild-type form of a gene that is mutated or abnormally expressed in tissues of a person with a genetic disease or other disease. Typically a virus is used to deliver the gene, and the DNA either inserts into the host chromosome or stays outside the cell nucleus in a virus that does not replicate. An example is adding a gene for glutamate decarboxylase to the brains of patients with a neurotransmitter deficiency in Parkinson’s disease (see Figure 15.18).

Question 3

In the past, it was common for people with phenylketonuria (PKU) who were placed on a low-phenylalanine diet after birth to be allowed to return to a normal diet during their teenage years. Although the levels of phenylalanine in their blood were high, their brains were thought to be beyond the stage when they could be harmed. If a woman with PKU becomes pregnant, however, a problem arises. Typically, the fetus is heterozygous but is unable, at early stages of development, to metabolize the high levels of phenylalanine that arrive from the mother’s blood.

  1. Why is the fetus likely to be heterozygous?

  2. What do you think would happen to the fetus during this “maternal PKU” situation?

  3. What would be your advice to a woman with PKU who wants to have a child?

  1. The mutation that leads to PKU is rare in the human population; most people do not have the harmful allele, and the highest probability is that the father is homozygous normal. Because the mother has PKU (she is homozygous mutant), the developing fetus is heterozygous.

  2. High levels of phenylalanine cause brain damage. If the mother’s phenylalanine levels were too high, the baby would be born with brain problems.

  3. The woman should be on a phenylalanine-restricted diet.

In this chapter you have learned about mutations, focusing on DNA changes that affect phenotypes through specific protein products. But there is much more to molecular genetics than the sequences of genes and proteins. Determining which genes will be expressed when and where is a major function of the genome. In Chapter 16 we will turn to gene regulation.