
The Family Gene - fern12
https://tuftsmagazine.com/issues/magazine/2017/spring/family-gene
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DoreenMichele
I wish the article had a clearer explanation of the mechanism of the
condition. Most genetic disorders involve a missequenced protein. From what I
gather, the defective protein is typically a thing the body intends to use as
a tool at the cellular level, but now you have either a defective tool doing a
lame job or a missing tool.

Anecdotally, cystic fibrosis also predisposes people to bloat, usually
concentrated in the belly. CF involves a defect in a cell channel that handles
trafficking of certain molecules into and out of the cell. There are a variety
of different defects in this channel, depending on the alleles involved.

I have a diagnosis of _atypical cystic fibrosis._ I have chronic belly bloat.
It used to be far worse and is also accompanied by fluid retention in the legs
and lower body.

Consuming hot peppers in combination with walking a great deal has helped to
reduce my fluid retention. I read up on capsaicin, the active ingredient, and
also spoke with a man with a PhD in chemistry about it. Capsaicin opens a
different cell channel and flushes fluid from the cell.

Lymph is circulated in part by the blood. It is basically the clear part of
blood, minus blood cells. It is called _interstitial fluid_ when it is out in
the tissues. Muscle action causes it to be moved back to the blood system at
much higher rates than the normal resting rate.

So it seems to me that if you are "leaking" lymph that has high levels of
protein in it, something has gone wrong with the mechanism involved in
returning lymph to the blood vessels. The protein probably does not come from
nutrients consumed. It probably comes from the muscle tissue.

A diseased liver can cause damage to the portal vein. The liver filters the
blood, removing toxic wastes. I imagine a disease that causes lymph to contain
high levels of protein would put enormous stress on the liver. It would not be
able to keep up with the filtering process.

The lungs filled with fluid because the body treats lungs and gut as
interchangeable systems to some degree. When you are at altitude, you cannot
breathe out wastes fast enough, so your body dumps them via urination. The
lungs and gut both interact with the body via the blood.

I would really be interested in knowing if they have identified a particular
cell channel or similar. To me, the explanation that this condition causes
high pressure in the portal vein and this causes lymph backup makes no sense.
It seems to me the high pressure in the portal vein would be a secondary or
tertiary consequence of whatever mechanism is causing lymph to accumulate.

/thinking out loud in public after midnight, no doubt a terrible mistake

~~~
patall
> Most genetic disorders involve a missequenced protein.

Most _known_ do, but thats just due to identification bias. We do not even
know how many genetic disorders there are. Nor how many people are affected.
Nor can we identify most of those that are of complex origin or due to larger
genomic alterations / structual variations.

~~~
yorwba
Can you give some examples of genetic disorders that do not involve a
missequenced protein? I can think of missing/duplicated chromosomes, but those
should be easier to detect than smaller differences.

~~~
hirenj
Lots more places things can go wrong not only before protein is synthesised,
but also after too.

An example is anything that hits a regulatory region for a protein (i.e.
outside protein coding region).

Chances are phenotype may not be as strong because you may end up with only
partial transcriptional loss. I'm guessing it's super critical where you have
developmental diseases, and you hit a TF binding site specific for
development.

