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NBME 17 Answers

nbme17/Block 0/Question#0 (reveal difficulty score)
The sequence surrounding the first two exons ...
Disruption of normal splicing by creation of a new 3' splice site ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
tags: biochem repeat

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submitted by โˆ—cassdawg(1780)
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This can be identified as a splice site mutation because:

  • It is not within the exon (coding region) so it cannot be a missense or nonsense mutation
  • Missense is the coding of the wrong amino acid
  • Nonsense is the premature insertion of a stop codon
  • It is occurring in the intron, and since the majority of splice sites are GT-AG, this causes an alternative splice site (see here)
  • Mutations are by definition an error that has been permanently incorporated into the DNA and thus the progeny of the cell so they are unlikely to interfere with replication (though mutations in the promotor region might interfere with transcription)
  • Polyadenylation occurs after translation and mutations (unless they are in the proteins responsible for polyadenylation) are unlikely to interfere with polyadenylation. PolyA polymerase does not require a transcript

Eukaryotic mRNA processing = FA2020 p41

Even without knowing the splice site mutation code, the answer can be inferred from elimination.

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sarahhjp  p418 FA 2020 B-thalassemia is caused by point mutations in splice sites and promoter sequences +6
imgdoc  Polyadenation occurs as a post transcriptional modification hnMRNA. Not after translation* +1



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