The Molecular Biology of Mutations and Muscular Dystrophy1

1. A mutation is a permanent change in a gene. What is a gene?

Different versions of a gene provide the instructions for making different versions of a protein which can result in different characteristics. This table shows how a mutated DMD gene can result in Duchenne muscular dystrophy.

Gene in DNA Protein CharacteristicsNormal DMD gene provides

the instructions to make normal dystrophin protein.

Normal dystrophinin muscle cells

Normal muscles and normal health

Mutated DMD gene does not provide the instructions to

make functional dystrophin.

No functional dystrophin

in muscle cells

Muscle cells break down, so child loses the ability to walk, develops heart problems, and typically dies as a young adult.

2. By about age 12, a boy who has Duchenne muscular dystrophy cannot walk and has to use a wheelchair. Explain how a mutated DMD gene can result in the inability to walk. Be specific.

3a. This figure shows how a gene provides the instructions to make a protein. Label each type of molecule in the figure and label the process represented by each arrow.

3b. Circle one of the codons in the mRNA.

3c. Explain what a codon is. Include the words “nucleotides” and “amino acid” in your answer.

1 By Dr. Ingrid Waldron, Department of Biology, University of Pennsylvania, ©2017. Teachers are encouraged to copy this student handout for classroom use. A Word file (which can be used to prepare a modified version if desired), teacher notes, and links to additional activities are

available at http://serendip.brynmawr.edu/exchange/bioactivities/mutation.

In this codon wheel the amino acids used to make proteins are shown in the outer circle. To identify the codons that specify an amino acid, start from the center where the first nucleotide in a codon is shown and move outward to the second and third nucleotides in the codon.

4a. Circle the amino acid Ser (serine; near the top right-hand corner).

4b. The codons that code for the amino acid Ser (= serine) are UCU, UCC, ______ and _______.

Translation of an mRNA molecule begins at a start codon (AUG). The stop codons indicate where translation ends.

5. In this table, circle each codon in the sequence of nucleotides in the mRNA molecule. Indicate the amino acids that would appear in the protein produced by translation of this mRNA sequence.

Sequence of nucleotides in mRNA AUGCGUUCAUGGACUSequence of amino acids in protein

6a. This figure shows translation, which is the process that adds the correct amino acid for each codon in the _______ molecule.

6b. The amino acid that the ribosome has just added to the growing protein molecule is specified by the UUU codon. Write in the abbreviation for this amino acid.

6c. Circle a tRNA molecule. Why are tRNA molecules needed so the ribosome can add the correct amino acid for each codon in the mRNA molecule?

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7a. The first column of the table below shows the beginning of a gene and five different mutations of this part of the gene. Use the base-pairing rules to complete the second column. For each mutation, write in any mRNA codons that will be changed as a result of the mutation and use check marks to indicate codons that will not be changed.

7b. Use the codon wheel on the previous page to identify any stop codons in the mRNA molecules. Circle the stop codons.

7c. use the codon wheel to complete the last column. For each mutation, write in any amino acids that will be changed and use check marks to indicate any amino acids that will not be changed. Use dashes to indicate any amino acids that will be missing as a result of a stop codon.

Beginning of gene in DNA First five mRNA codons Beginning of ProteinOriginal DNA =

TACGCAAGTACCTGA… AUG CGU UCA UGG ACU Met – Arg – Ser – Trp – ThrMutation 1 =

TACGCCAGTACCTGA… (nucleotide change underlined)

___ ___ ___ ___ ___ ___ ___ ___ ___ ___

Mutation 2 =

TACGCACGTACCTGA… (nucleotide change underlined)

___ ___ ___ ___ ___ ___ ___ ___ ___ ___

Mutation 3 =

TACGCAAGTACTTGA… (nucleotide change underlined)

___ ___ ___ ___ ___ ___ ___ ___ ___ ___

Mutation 4 =

TACGAAGTACCTGA… (second C deleted)

___ ___ ___ ___ ___ ___ ___ ___ ___ ___

Mutation 5 =

TACGCAAGTACTGA… (third C deleted)

___ ___ ___ ___ ___ ___ ___ ___ ___ ___

8. Explain why one of the above mutations did not result in any change in the amino acid sequence of the protein.

9a. A point mutation is a change in a single nucleotide in a gene. Which three of the above mutations are point mutations? 1 ___ 2 ___ 3 ___ 4 ___ 5 ___

9b. Which of these point mutations would have the biggest effect on the protein produced? Why?

10. Deletion of a single nucleotide in a gene often results in a very defective protein. Explain why.

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There are many different mutated versions of the DMD gene. Some of these mutations cause Duchenne muscular dystrophy, but others cause a milder disease called Becker muscular dystrophy.

Duchenne muscular dystrophy is more severe. A boy with Duchenne muscular dystrophy typically begins to show muscle weakness by age 5 and needs to use a wheelchair by age 12. He usually dies in his twenties, due to heart failure. His muscle cells died because they had no functional dystrophin, due to a mutation in his DMD gene.

Becker muscular dystrophy is milder. Symptoms do not begin until age 12 or later, and a person with Becker muscular dystrophy often survives into his forties. His muscle cells have an abnormal version of dystrophin that is somewhat effective for keeping muscle cells alive.

11a. The majority of muscular dystrophy cases are caused by deletion mutations. These deletion mutations can be grouped into two categories:

a. The number of nucleotides omitted from the mRNA is a multiple of 3.b. The number of nucleotides omitted from the mRNA is not a multiple of 3.

Which type of mutation causes the more severe Duchenne muscular dystrophy? ____Which type of mutation causes the milder Becker muscular dystrophy? _____

11b. Explain your reasoning.

12a. As shown in this figure, the DMD gene is located on the X chromosome. A carrier mother has one normal DMD gene and one mutated DMD gene. She does not have muscular dystrophy. Which version of the gene is recessive?

___ normal DMD gene___ mutated DMD gene

12b. Explain why Duchenne muscular dystrophy is very rare in girls, and most Duchenne muscular dystrophy patients are boys.

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