WHAT HAPPENED TO THE DNA?

(How mutations lead to variation within a gene)

The idea for this activity originated with Ricki Lewis, Human Genetics, Concepts and Applications, second edition, 1997, p.198, and was modified by Lori Buwalda and Barb Neureither.

In this activity, we will use the three letter words in a sentence to model the effect of different mutations on a sequence of DNA and its resulting protein. In each sentence:

Original:
THE BIG FAT BUG BIT THE BIG FAT CAT

Mutation A:
THE BIG FAT BUG MIT THE BIG FAT CAT
Describe the change (mutation):

Mutation B:
THE BIG FAT BUG BIT GTH EBI GFA TCA
Describe the change (mutation):

Mutation C:
THE BIG FTB UGB ITT HEB IGF ATC ATT
Describe the change (mutation):

Mutation D:
THE BIG FAT
Describe the change (mutation):

Mutation E:
THE BIG FAT BUG BIT THE BIG
Describe the change (mutation):

Mutation F:
THE BIG FAT BUG BIT THI BIG FAT CAT
Describe the change (mutation):

QUESTIONS

1. Mutation A and Mutation F are both missense mutations, where a single codon is changed and results in a single amino acid change. Compare these two mutations and hypothesize which would cause the greatest change in the protein and why?

2. Mutation B and Mutation C both result in a frameshift. Mutation B inserts an extra nucleotide and Mutation C removes a nucleotide, both result in a shift of the reading frame for the codons and that is why it is called a frameshift. Compare these two mutations and hypothesize which would cause the greatest change in the protein and why?

3. Mutation D and Mutation E are both nonsense mutations. Their proteins end abruptly because a mutation has caused one of their codons to be changed to a stop codon resulting in a sudden ending to the protein sequence or a STOP in the protein synthesis. Compare these two mutations and hypothesize which would cause the greatest change in the protein and why?

4. Now compare the three types of mutations represented here, missense, frameshift, and nonsense. Which type(s) could cause the greatest change in the resulting protein? Explain.

What does all of this have to do with CANCER and other chronic disorders? The best way to explain this is with an example.
BRCA1 is a gene that if inherited it will increase your chance of developing breast cancer. At the site for this particular gene (chromosome 17q21) scientists have discovered several genetic variations for the gene that were probably caused by mutations. In fact they have discovered all three of the mutations described above. Each mutation will most likely have a different effect on the protein it produces and consequently on the phenotype for the cancer. It would be helpful if scientists knew which form was found in a tumor so they could prescribe the best treatment. How do they tell which mutation is present? They are starting to use microarrays or DNA chips to tell them which genes are functioning and what genetic variants are present. To find out more, check out the tutorials and activities for microarrys under Genetic Variation.

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