3 ms·

I wonder how this genetic error could propagate wide enough for the disease to get a name. It's clearly maladaptive, isn't it? Of course, same question could

I wonder how this genetic error could propagate wide enough for the disease to get a name. It's clearly maladaptive, isn't it? Of course, same question could be asked for BRCA.

dEnigma 9y ago
See my other comment for a possible explanation. There seems to be a link between complex brain development and Chorea Huntington, where a higher number of triplets in the gene leads to higher intelligence or more complex brains, but when the number gets too high the disease develops.
philjohn 9y ago
Because it usually only kicks in after childbearing years, until relatively recently there's not been a test for it, so no way to know if you'd pass it onto your children, and in the last 200 years life expectancy has gone past the age at which is kicks in, highlighting it more.
- thriftwy 9y ago
  > Because it usually only kicks in after childbearing years Orphans are not a very good evolutionary tactics. But you definitely have a point otherwise. Had it earlier onset age, it would have no way to propagate.
  - Retric 9y ago
    Historically 30-50 would be often be grandparents or great grandparents which has much less evolutionary pressure. Though they would likely still have underage kids.
    - carlmr 9y ago
      Historically those kids would have been working already.
      - Retric 9y ago
        A 50 year old can have great grand kids, and a 3 year old at the same time. Though with a large extended family someone can also probably take over in the case something happens.
  - taneq 9y ago
    Do you still call them "orphans" if they're in their mid to late 20s?
Real_S 9y ago
There is something important about the type of mutations that drive Huntington's. Huntington's is caused by an expanded repeat composed of (CAG)n with n>40 repeats. Due to the instability of repeat regions, new mutations arise in this gene at a relatively high rate. So, even if there were strong selection against expanded repeats the disease would continue to exist. However, as mentioned by others here, strong selection is unlikely due to the late age of onset of the disease. So mutation continues to introduce the disease and selection has been too weak to remove it. In contrast, BRCA mutations differ from the Huntington mutations. BRCA mutations are single "point" changes in the sequence, known as SNPs, that disrupt the protein function. Novel point mutations are exceptionally rare. So, unlike with BRCA, when investigating why Huntinton's disease exists, one must consider BOTH mutation and selection.
- fossuser 9y ago
  Huntington's also has an interesting place in the history of genetics, genetic diseases, and heredity. I wish I could find the excerpt, but the book The Gene talks about the original research and it's an interesting story. The book is worth reading in general (Siddhartha Mukherjee is a great writer and it's really good). http://www.simonandschuster.com/books/The-Gene/Siddhartha-Mukherjee/9781476733500 http://www.simonandschuster.com/books/The-Gene/Siddhartha-Mu...
ouid 9y ago
I don't think it's clearly maladaptive. We age and die because it's adaptive to do so. It's possible we've retained a predilection for developing huntington's because it's energy efficient to have some grandparents die. I'm not arguing that this is necessarily the case, but it is not clearly maladaptive.

I wonder how this genetic error could propagate wide enough for the disease to get a name. It's clearly maladaptive, isn't it? Of course, same question could be asked for BRCA.

dEnigma 9y ago

See my other comment for a possible explanation. There seems to be a link between complex brain development and Chorea Huntington, where a higher number of triplets in the gene leads to higher intelligence or more complex brains, but when the number gets too high the disease develops.

philjohn 9y ago

Because it usually only kicks in after childbearing years, until relatively recently there's not been a test for it, so no way to know if you'd pass it onto your children, and in the last 200 years life expectancy has gone past the age at which is kicks in, highlighting it more.

thriftwy 9y ago
> Because it usually only kicks in after childbearing years Orphans are not a very good evolutionary tactics. But you definitely have a point otherwise. Had it earlier onset age, it would have no way to propagate.
- Retric 9y ago
  Historically 30-50 would be often be grandparents or great grandparents which has much less evolutionary pressure. Though they would likely still have underage kids.
  - carlmr 9y ago
    Historically those kids would have been working already.
    - Retric 9y ago
      A 50 year old can have great grand kids, and a 3 year old at the same time. Though with a large extended family someone can also probably take over in the case something happens.
- taneq 9y ago
  Do you still call them "orphans" if they're in their mid to late 20s?

Real_S 9y ago

There is something important about the type of mutations that drive Huntington's. Huntington's is caused by an expanded repeat composed of (CAG)n with n>40 repeats. Due to the instability of repeat regions, new mutations arise in this gene at a relatively high rate. So, even if there were strong selection against expanded repeats the disease would continue to exist. However, as mentioned by others here, strong selection is unlikely due to the late age of onset of the disease. So mutation continues to introduce the disease and selection has been too weak to remove it. In contrast, BRCA mutations differ from the Huntington mutations. BRCA mutations are single "point" changes in the sequence, known as SNPs, that disrupt the protein function. Novel point mutations are exceptionally rare. So, unlike with BRCA, when investigating why Huntinton's disease exists, one must consider BOTH mutation and selection.

fossuser 9y ago
Huntington's also has an interesting place in the history of genetics, genetic diseases, and heredity. I wish I could find the excerpt, but the book The Gene talks about the original research and it's an interesting story. The book is worth reading in general (Siddhartha Mukherjee is a great writer and it's really good). http://www.simonandschuster.com/books/The-Gene/Siddhartha-Mukherjee/9781476733500 http://www.simonandschuster.com/books/The-Gene/Siddhartha-Mu...

ouid 9y ago

I don't think it's clearly maladaptive. We age and die because it's adaptive to do so. It's possible we've retained a predilection for developing huntington's because it's energy efficient to have some grandparents die. I'm not arguing that this is necessarily the case, but it is not clearly maladaptive.