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Is the impact of a frameshift mutation restricted to the exon in which it occurs?

Is the impact of a frameshift mutation restricted to spoiling the exon in which it occurs but not the intronic sequences or next exones?

frameshift mutation
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updated by WouterDeCoster WouterDeCoster • written by lamteva.vera lamteva.vera

An interesting example of the consequences of frameshift mutation:

"This duplication of one nucleotide in BRCA2 is denoted c.9253dupA at the cDNA level and p.Thr3085AsnfsX26 (T3085NfsX26) at the protein level. The normal sequence, with the bases that are duplicated in braces, is GAAAAAA[A]CAGG. The duplication causes a frameshift, which changes a Threonine to an Asparagine at codon 3085, and creates a premature stop codon at position 26 of the new reading frame" [ClinVar]

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written by lamteva.vera lamteva.vera

2 answers

A frameshift mutation can affect the whole transcript which the exon is part of. Intronic sequences are spliced out so are more likely to be unaffected. However, introns may contain regulatory mechanisms such as enhancers etc.

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written by colindaven colindaven

Indeed, it is very difficult to predict the effects of frameshift mutations, and even non-frameshifts. A frameshift in a single exon could potentially open up an entire new transcript isoform by extending the coding region further into what were originally introns (depending on the sequence).

There are likely a whole bunch of consequences of frameshifts that we don't yet fully understand.

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written by Kevin Blighe Kevin Blighe

An interesting example of the consequences of frameshift mutation:

"This duplication of one nucleotide in BRCA2 is denoted c.9253dupA at the cDNA level and p.Thr3085AsnfsX26 (T3085NfsX26) at the protein level. The normal sequence, with the bases that are duplicated in braces, is GAAAAAA[A]CAGG. The duplication causes a frameshift, which changes a Threonine to an Asparagine at codon 3085, and creates a premature stop codon at position 26 of the new reading frame" [ClinVar]

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written by lamteva.vera lamteva.vera

In general: an out-of-frame frameshift will disturb the reading frame and very likely lead to a premature stop codon (leading to nonsense-mediated mRNA decay).

As always in biology, there are exceptions.

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written by WouterDeCoster WouterDeCoster

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