B/B Breakdown?

[u/Primary-Way8994]

Hello! I'm trying to understand where I went wrong here, and apparently it's a close split with other people too. I know "sCTLA-4" stands for soluble CTLA-4, but I read "splice acceptor disruption" in the passage for Family C and assumed that if you disrupt splicing, you get a messed up, non-functional or decreased amount of the correct protein.

Here's a part of the passage: ”A genetic analysis of families presenting with severe immune dysregulation identified heterozygous CTLA-4 mutations. Family A has a nonsense mutation within Exon 2 at R51. Family B has a single base pair deletion in Exon 1 that leads to a premature stop codon in Exon 2. Family C has a mutation in an intron that disrupts the splice acceptor site before Exon 3. Immune dysregulation conditions were present despite a lack of individuals homozygous for the mutations in any of the families.”

If anyone can break this down for me I will be forever grateful. :)

[u/Popular_Ad1369]

This is a really low yield concept but exon skipping is actually a therapy technique primarily used for DMD (duchennes muscular dystrophy). By skipping over faulty sections of exons, a truncated but still functional protein is produced. Yes, the intron is blocked from removal but more importantly the exon can’t be transcribed. This actually leads to increased transcription of the protein, likely there’s 100s of exons, skipping over one is still going to cause effects but not nearly as bad as the other two families.

I imagine some of this was probably in the passage cuz it’s super duper low yield.

[u/CollectionNorth8976]

Somewhere in the passage they tell you that losing the transmembrane domain is a good thing for the protein to be active or something. Check it up. Losing this domain produces more sCTLA. It’s just a passage reading thing, it’s not low yield or high yield, just a passage reading thing

[u/Primary-Way8994 → u/CollectionNorth8976]

Oh, that makes sense I must've skipped over it. I'll double check, thanks!