Can splice-site mutations be treated as gene knock-outs?
Entering edit mode
5.3 years ago

I'm working with some exome-sequencing data that's been run through a mutation calling pipeline. My goal is determine which samples have deactivating mutations within a subset of genes. Using the MAF column "Variant_Classification", I've already decided to mutations with values like "stop_gained" and "start_lost" are indications that the gene is effectively knocked-out. But I don't know what to do about splice-site values like: "splice_acceptor_variant" "splice_donor_variant" "splice_region_variant"

Should I just treat all splice-site mutations as an indication that the gene product won't function properly and therefore it's effectively been knocked out? Are some types of splice-site mutations more likely than others to prevent the gene product from functioning?

I haven't been able to find any literature addressing this question so I thought I'd ask here.

SNP sequencing • 1.1k views
Entering edit mode
5.2 years ago

Without any supporting literature at hand: no.

Splice sites mutations may:

  • just reduce correct splicing and therefore expression by a bit without creating a full knock out
  • result in alternative splicing in which another transcript is produced (e.g. exon skipping), which can be not, partially or fully functional
  • indeed result in a knock out

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