Whole Exome Sequencing May Skip Large Segments of DNA

academic.oup.com

24 points·bookofjoe··7 comments

“Clinical Exome Studies Have Inconsistent Coverage” seems like a significantly better title. The current HN one doesn’t make sense.

Precisely, if it's not skipping large segments of the genome it's not exome sequencing, that's the entire reason that we do exomes instead of WGS.

Weird this is here... this is a well known result, such studies have been coming out for at least 5 years.

The value proposition for whole exomes is diminishing as sequencing itself gets cheaper ie might as well do a whole genome. Exomes are still useful in some situations, eg cancer or formalin fixed tissue.

Whole genomes bring their own complications. You will have tons of variants of unknown significance in each patient. Then you would want functional data to see if there is an impact on transcription/translation of the protein, and the tissue of interest might not be accessible for such an analysis. There is some interesting stuff on the horizon—like humanizing homologous genes in C. elegans and CRISPRing in the mutation of interest, then doing functional studies in the worm. Not perfect, but it could give you functional information in a clinically relevant time frame.

Worth noting that the sequencing for this analysis was performed from 2012-2016. 4 years is a long time in the NGS world, and it is highly likely there have been chemistry improvements since then. Though it wouldn’t surprise me if inconsistency in coverage in clinical whole exomes remains.

Probably at start of first exon and end of last exon. Or regulatory regions before them.

edit title to say "segments of genes"

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