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I work in an adjacent area and agree this is all good advice. OP, how did you even get the sequence to begin with? I have a friend who has an immunodeficiency which is almost certainly due to a rare genetic disorder and want to do a very similar thing. Despite contacting his physician, fellow researchers, and even my institution's president -- with friend's full cooperation -- no one is willing to pay for it. I'm at my wit's end to the point that I'm starting to think the only viable option is paying for it out of pocket, but it's not cheap. A question you might want to ponder is: suppose you isolate the problem to a single missense/nonsense/truncation mutation in a protein that seems likely to cause the phenotype. How do you plan to use that information? In theory, there is gene therapy, but in reality, given how much effort I have had to go through just to get this fellow sequenced -- and I'm a PhD working in genomics with a lot of contacts -- creating a custom one-off gene therapy solution seems like it would be a very tremendous undertaking. There is a very difficult problem here in that rare or "personalized" disease treatments are: A) not profitable, so drug companies have no interest, B) there are mountains of paperwork, IRBs, consent waivers, etc, involved in developing an experimental therapeutic, C) by definition you cannot do a proper clinical trial on a one-off, and D) it requires several different types of expertise to pull such a thing off. Sadly this means that it almost never happens, even though I suspect there are a lot of severe and lifelong genetic disorders which could be diagnosed and treated with technology available today. Based on my experience so far, I suspect that even if you were to hand his physician very strong evidence that "the problem is caused by this specific single mutation", the response will be "OK, thanks". You should not make strong assumptions about them being able to take it from there. All this is based on the best-case scenario of it being a single variant in a coding region; if the disorder is caused by multiple variants at different loci, anything you find will probably not be actionable. |
My neurologist ordered sequencing for me from Invitae, to determine the subtype of Ehlers-Danlos I have and rule out neuromuscular diseases. She said insurance usually covers it, and it's only a few hundred bucks if they don't. Invitae appears to do WGS for such panels. I've also heard of Nebula genomics offering affordable WGS and exome sequencing.
She said she'd take a look at the results, and if anything popped out as unusual, I'd see a geneticist.
> A question you might want to ponder is: suppose you isolate the problem to a single missense/nonsense/truncation mutation in a protein that seems likely to cause the phenotype. How do you plan to use that information?
Identify the molecular pathway involved and see if there's any drugs available that might modulate it in a therapeutic way. You might also identify similar diseases that might share similar treatments, once you know the etiology.
Once a mutation or gene responsible is identified, other patients can be as well, which can slowly lead to mouse models and clinical trials etc.