
How One Sickle Cell Mutation Helped Protect the World from Malaria - tysonzni
https://www.nytimes.com/2018/03/08/health/sickle-cell-mutation.html
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jfarlow
It turns out that if you want to correct sickle cell disease, you (just) have
to revert the single the bit of genetic instruction that permits hemoglobin
proteins to atomically interlock like legos. The aggregation only occurs when
the protein structures are well-suited to aggregation. A single atomic
'feature' on the protein is the difference between a protein that aggregates
easily and one that does not.

 _Further_ , there is actually a separate mutation to the hemoglobin protein
that actively disrupts the interlocking of even those hemoglobins that would
otherwise do so. So the presence of an additional atomic feature or bump on
the protein actually inhibits aggregation when intermixed with proteins that
would otherwise aggregate.

Companies [1] are right now developing gene therapies [2] that introduce that
'upgraded' version of hemoglobin in patients. The upgraded hemoglobin has a
mutation from a threonine to a glutamine at position 87 of wild-type human
hemoglobin:
[https://serotiny.bio/notes/proteins/hbb/](https://serotiny.bio/notes/proteins/hbb/)

[1] [https://www.bluebirdbio.com/our-focus/severe-
diseases/](https://www.bluebirdbio.com/our-focus/severe-diseases/)

[2]
[http://www.nejm.org/doi/full/10.1056/NEJMoa1609677?query=fea...](http://www.nejm.org/doi/full/10.1056/NEJMoa1609677?query=featured_home&)

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tathougies
Hemoglobin is an interesting molecule. There are a lot of variations, and even
the 'bad' variations aren't always 'bad' for everyone. I believe there is a
significant portion of those with homozygous sickle cell trait (meaning they
ought to have full on sickle cell anemia) who don't show any symptoms. I have
thalassemia (a similar hemoglobinopathy), but I also carry the hereditary
persistence of fetal hemoglobin (I basically have baby blood), which means --
if i were to have sickle cell anemia -- it wouldn't affect me as much, and my
anemia symptoms from the thalassemia are greatly lessened.

There's a ton of other variations that can ameliorate all these things too.
That's just my knowledge on one. In fact, for those with full-on thalassemia
(or sickle cell too), they frequently give hydroxyurea, which causes the bone
marrow to produce fetal hemoglobin, to aleve the anemia symptoms.

It's all very interesting

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danieltillett
_Some West Africans captured in the slave trade brought the sickle cell
mutation to the Americas. But in places like the United States, where malaria
was uncommon or nonexistent, the mutation offered less of an evolutionary
advantage. As a result, African-Americans have a lower rate of sickle cell
anemia than Africans today._

I can't beleive how wrong the journalist got this paragraph. The whole reason
for the African slave trade was Malaria as the European "slaves" (poor
indentured workers) could not survive in the US south because of Malaria which
was very common until the 20th C. Also the reason the rate of Sickle Cell is
lower is USA is there has been a significant amount of European geneflow
(~30%) into the African American population.

I should add that while the selection pressure has been lower in the USA, this
has not been the major reason for the lower rate.

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Lordarminius
I agree with you, clearly the writer has got his science mixed up.

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nkozyra
But aren't you describing a statistical side effect? It's not as though this
mutation imparts a 100% chance of having sickle cell anemia. If 87.5%
(carriers and non carriers) survive significantly longer due to malaria
resistance and 12.5% lack that extended lifespan due to anemia, isn't it still
an advantage overall?

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Lordarminius
deleted

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nkozyra
What I'm saying is even if it was 100% infant mortality, the statistical odds
of getting it still leaves the malarial resistance as a genetic advantage.

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Lordarminius
Sorry. I don't get your point.

Assuming 100% mortality, how could there possibly be an advantage if the genes
of the afflicted cannot be propagated ?

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tysonzni
People who have sickle cell anemia still have a life expectancy of years (>40
in US). On the other hand, getting malaria usually means you mortality is
measured in days not years. Everyone has a "100% mortality" but the window of
survival differs between diseases.

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maury91
This is another blood mutation that spread across Europe because it can
protect from malaria:
[https://en.wikipedia.org/wiki/Beta_thalassemia](https://en.wikipedia.org/wiki/Beta_thalassemia)

It's another example of odd evolution, people with Thalassemia minor were able
to survive malaria, and because they were able to remain alive, they spread
their genes, increasing the pool of people with Thalassemia

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maury91
This blood mutation is so common in Sardinia, that 20% of the population is a
carrier
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1013759/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1013759/)

