Short videos can be used as case studies by stopping at appropriate time points and asking questions to cue student attention, encourage critical thinking, and make the students part of the story.
This video case study focuses on a real-world problem: identifying genetic mutation(s) associated with diseases. It is appropriate for a range of biology courses, including AP/IB Biology and college-level introductory biology.
Student Learning Targets
- Formulate a hypothesis to explain how a mutation in a gene would affect the function of a cell and an organism.
- Describe the possible steps involved in identifying a disease-causing gene mutation in a patient.
- Predict how replacing a mutated gene with a functioning copy of that gene will affect the phenotype of a cell and/or organism.
- Explain how the identification of disease-causing mutations can be used to develop medical treatments.
Prior Knowledge
Students should be familiar with the definition of mutations and how genetic mutations can be inherited. Students should also be familiar with the process of gene expression.
Background Information
- Most human traits, including diseases, are influenced by multiple genes. It is difficult to develop genetic therapies for diseases caused by variations or mutations in many genes (multigene diseases). However, a relatively small number of genetic diseases are caused by mutations in single genes (single-gene diseases). It’s more feasible to identify mutations for single-gene diseases and develop effective therapies.
- Retinitis pigmentosa (RP) is a progressive visual disease that causes photoreceptor cells in the retina to die. It is caused by mutations in any one of several different genes. Mutations in any one of these genes are sufficient to cause RP.
- Many mutations that cause RP have been identified. When scientists tested the DNA of the patient featured in this video, Sam, they did not find any of these known mutations.
- Scientists determined that Sam’s DNA contains a previously unknown mutation that affects tRNA structure and function. They then discovered that two other patients with RP have mutations in the same gene.
- Scientists were able to confirm that the mutation affects photoreceptor cells through experiments in zebrafish, a model research organism.
The video case study is presented in eight modules, each followed by embedded questions. Educators can use the extension questions listed below for additional class discussion or written assessments.
Modules 1 and 2 establish the genetic basis of RP and describe other features of the disease. Prior to starting the video, prompt students by asking what they know about gene therapy. Following a brief discussion, start viewing the module. The first module ends by asking students questions about the inheritance pattern of RP. In the second module, students consider how genetic analysis of DNA from blood samples of related individuals could be used to identify the causative mutation.
Extension questions:
- How do our brains convert information from light entering our eyes into an image?
- What is disease? How do organisms get diseases?
- What is a genetic mutation and what are its effects?
- How is searching for a treatment for a genetic disease different from that for a disease caused by something else, such as bacteria or viruses?
Module 3 explains how comparing the DNA of relatives can identify a mutation that causes disease and how this approach has been used to identify many different mutations that cause RP. The module ends by asking students to explain how one disease can be caused by any one of many mutations.
Extension questions:
- Why would a researcher use a pedigree to study a disease?
- Many characteristics of an organism are controlled by more than one gene. Likewise, many of the biochemical processes and pathways involve proteins produced by different genes. Explain how this relates to the existence of many different mutations that cause RP.
- Can you think of any other diseases or conditions that are caused by mutations in different genes?
Modules 4 and 5 explore how a genetic scan of Sam’s genome did not find any of the known common or rare mutations that cause RP. Instead, Sam’s DNA has a mutation that had never been identified as a possible cause of RP. These two modules end with questions asking students to interpret the results of the genetic analysis and predict the impact of the mutation affecting Sam’s tRNA function.
Modules 6 reveals how a mutation that affects tRNA function is not necessarily lethal. The mutation in Sam’s DNA reduces tRNA function but does not completely stop protein synthesis. Knowing this, students are asked what additional data they would need to collect as evidence that the mutation in Sam’s DNA causes RP.
Extension question:
- Some mutations are lethal and others are not. Explain the difference between these two types of mutations in terms of cellular function.
Modules 7 and 8 conclude the case study by demonstrating the experimental procedure used to confirm that the mutation in Sam’s DNA causes RP. By genetically engineering zebrafish, a model organism, to have a mutation in the same gene, scientists demonstrated that the mutation impacts how zebrafish respond to light. With this information, students conclude the case study by predicting how gene therapy could be used to treat RP and the outcomes for patients’ vision. The final module concludes by asking students to explain the benefits of identifying mutations that cause disease.
Extension questions:
- In your own words, explain why researchers use model organisms such as zebrafish. Can you name any other model organisms?
- Genetic medicine is an emerging technology that holds great promise for many diseases. Are there any ethical concerns with genetic medicine as described in this case study? Explain your perspective.
- Are there any other diseases you know of that currently are or could potentially be treated or cured through genetic medicine?
- Search newspapers, magazines, or the scientific literature for diseases being treated through genetic medicine. Have there been successes? Failures?