why do frameshift mutations result in truncated mRNA? UW q1412

[okokok]

UW q ID 1412 describes the comparison of DNA between a child with CF and his brother. Regarding the pertinent gene, the affected child has mRNA that is 101 bp, the unaffected child has mRNA that is 129 bp long. The question asks: "Which of the following is most likely responsible for the patient's condition?" and lists all the different mutations. The correct answer is frameshift mutation. 29% of people chose frameshift mutation, 44% chose nonsense mutation.

Questions:
1. The stem didn't explicitly say the kid had CF, but made it pretty clear (mentions he has pneumonia, bronchitis, cough, and a genetic test reveals a mutation in an exon of a gene that codes for a transmembrane chloride channel). Was I supposed to know it was a frameshift mutation based on that? (I was one of the 44% nonsensers)

2. The answer explanations for why missense and nonsense mutations are wrong say that these would not alter mRNA length as it only affects protein translation. It's not clicking for me why a frameshift mutation would affect mRNA length?

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[zhopv10]

So a frame shift can be a deletion or an addition of a non multiple of 3 amount of base pairs. In the case of a truncated mRNA it was probably a deletion of some number of bases. As mentioned the others affect the protein not the mRNA length


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[dorster]

just to go along with what zhopv10 is saying.. I also had this question and like you put nonsense mutation (feels weird to be in the majority and still get the question wrong haha). But I realized that a nonsense mutation is a substitution mutation in the DNA which then causes a stop codon to be inserted in the mRNA. SO like for example if the DNA sequence was GCT(TCA)GCT--> and then it got changed to GCT(TCT)GCT due to a mutation the complementary mRNA strand would now be CGA(UGA)CGA see how the codon in the middle now became a stop codon. The size of the mRNA doesn't change but when the protein is created it will now only be 1 amino acid long instead of 3 amino acids long. This is an example of nonsense mutation where the protein size is shortened but the mRNA size doesn't change. nonsense mutations are usually so dysfunctional that the protein doesn't even work. Whereas frameshift mutations are usually from deletions or insertions and so they would change the size the mRNA AND the protein as well. The key is that a nonsense mutation is due to a nucleotide substitution (not deletion or insertion) so the size of the mRNA doesn't change.

 

[okokok]

So a frame shift can be a deletion or an addition of a non multiple of 3 amount of base pairs. In the case of a truncated mRNA it was probably a deletion of some number of bases. As mentioned the others affect the protein not the mRNA length


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Ok so the mutation is a deletion of 28 bp's? I guess I just wasn't thinking the "mutation" (I always think of a point mutation, erroneously) would be such a large deletion. But I get it now, thanks.

 

[zhopv10]

Yups, I know it's weird I do the same thing (I too fell for the nonsense mutation trap originally haha)


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