To determine which change in an exon is most likely to result in a nonfunctional protein product, let's analyze each option:
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A substitution in the last base of a codon: This is referred to as a "silent mutation" if it doesn't change the amino acid due to the redundancy in the genetic code. However, if it does change the amino acid, it could potentially alter the function of the protein, but not necessarily result in a nonfunctional protein.
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A base-pair deletion: This introduces a frameshift mutation, which alters the reading frame of the codons downstream of the deletion. This is very likely to result in a nonfunctional protein because it can change many amino acids in the protein and potentially lead to a premature stop codon.
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A codon deletion: This removes one codon (three nucleotides), which will affect one amino acid in the protein. It might disrupt protein function, but it is less likely to render the protein completely nonfunctional compared to the frameshift.
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An addition of three nucleotides: This adds a codon, and while it changes the protein by adding an amino acid, it does not cause a frameshift. The protein may still be functional, though it could affect its function depending on where and how the new amino acid is introduced.
Based on this analysis, the change that is most likely to result in a nonfunctional protein product is:
A base-pair deletion.