The sequence of nitrogen bases along a DNA strand can be thought of as the recipe or list of ingredients to make proteins, which our bodies need to function properly. Any change or variation to this ingredient list can influence the “final product,” and in genetic terms this is known as a mutation.
In this lab activity, we will apply what we have learned about DNA and protein synthesis to predict the outcome of various mutations, focusing on the human gene for dystrophin. Dystrophin is a protein that helps build healthy muscle, and mutations in the associated gene can lead to the disease Muscular Dystrophy (MD). MD is a group of diseases that cause progressive weakness and loss of muscle mass. There are many different kinds of MD, and symptoms of the most common variety begin in childhood. Some people who have MD will eventually lose the ability to walk, or have trouble breathing or swallowing. There is no cure for MD, but medications and therapy can help manage symptoms and slow the course of the disease.
Here we are focusing on the relationship between mutations and disease, but it is important to remember that the vast majority of mutations are actually “neutral”, meaning they have little to no direct impact on an organism’s ability to survive and reproduce. Furthermore, mutations increase genetic diversity, which is key to the success and continuation of all populations (a point we will return to in a future lab).
You will be conducting genetic research, working with DNA samples from twin brothers. Liam has MD, but his twin brother Elijah does not. After comparing Liam and Elijah’s DNA sequences for the dystrophin gene, you have identified five differences and specified their locations within the DNA sequences (Table 1). The sequence for Elijah’s “normal” dystrophin gene is also provided below. Use this information in combination with the material from the DNA & Protein Synthesis Module to answer the following questions and predict which of the five mutations in Liam’s DNA is the most likely cause of his MD. HINT: Assume that both Elijah’s and Liam’s sequences produced a protein.
Elijah’s “Normal” Dystrophin Sequence
In the DNA sequence listed below, Exon segments are denoted by capital letters, and intron segments are denoted by lowercase letters
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