3 ms·

Infertility rates are extremely high for individuals with Down’s syndrome, so it’s very uncommon to pass on Downs Syndrome from an adult with Down’s to a child

im3w1l 3y ago
Given that Down Syndrome is caused by an extra chromosome, I'm kinda curious how that would be inherited. Like if you have two people with Down's would there be a possibility of offspring with an extra chromosome pair? Could that in the long term lead to speciation? Would it be possible that only one of the three chromosomes is passed on from each parent, leading to a normal and healthy child?
- thereticent 3y ago
  It's an interesting topic. The primary cause of Down syndrome is trisomy of chromosome 21, which is what you described. That form is not inherited. A much less common cause, mosaicism, is a random occurrence during cell division and isn't inherited either. The only form that can be inherited (that we know of) is caused by translocation. Basically a piece of one chromosome can become switched with a piece of another chromosome. If no information is lost, that's a balanced translocation. Those usually still produce a normal phenotype. When the balanced translocation is passed down a generation, it can lose information or pick up extra information and become unbalanced. If the extra information is from chromosome 21, that can become Down syndrome. That's a simplistic explanation, but should do the job.
  - im3w1l 3y ago
    Right that makes sense. I guess what happens in all of these scenarios is having an extra copy of one particular gene, causes it to become overexpressed, which in turn leads to all these issues?
    - thereticent 3y ago
      It's actually many, many genes that are overexpressed and result in the Down syndrome phenotype. My work is with adults with DS and Alzheimer disease--in this case, triplication of the amyloid precursor protein (APP) gene on chromosome 21 nearly guarantees accelerated development of cerebral amyloid deposition compared to typically developing people. But that's just a miniscule part of the Down syndrome phenotype.
  - thereticent 3y ago
    It's actually many, many genes that are overexpressed and result in the Down syndrome phenotype. My work is with adults with DS and Alzheimer disease--in this case, triplication of the amyloid precursor protein (APP) gene on chromosome 21 nearly guarantees accelerated development of cerebral amyloid deposition compared to typically developing people. But that's just a miniscule part of the Down syndrome phenotype.
- RoyalHenOil 3y ago
  >Like if you have two people with Down's would there be a possibility of offspring with an extra chromosome pair? Could that in the long term lead to speciation? A similar phenomenon is common in plants. While humans have two copies of DNA, one from each parent, many plants contribute more than one copy of DNA to their offspring, resulting in plants with many more than just two copies of DNA. The number of copies a plant has can vary within the same species. Notably, domesticated plants often have more copies of their DNA than their wild counterparts have, yet they are still reproductively compatible. In animals like us, multiple copies of DNA, or even just of individual chromosomes, are much more risky, which is why it's so rare (those embryos are typically nonviable). However, different animal species do often have different numbers of chromosomes, which does provide a pathway to evolutionary divergence and speciation. Typically, species with different numbers cannot reproduce (e.g., humans and chimps), and when they can, the result is often sterile (e.g., horses and donkeys). There are several ways that species can gain or lose new chromosomes as they evolve, and you are right: duplication of an existing chromosome is one of them, although pretty rare because it often leads to serious health problems or sterility. (More common is the splitting of a chromosome or the fusing of two chromosomes, since these preserve all the genes without duplication. Another possibility is the total deletion of a chromosome, but this is extremely rare because it typically kills the embryo.) So yes, theoretically, fertile men with trisomy 21 Down's syndrome (they are usually sterile, but there have been exceptions) and women with trisomy 21 Down's syndrome could get together and start a new hominid branch. Over time, the twin chromosomes would undergo selection and diverge from one another, likely in a way that would improve on the general health and fertility issues that people with this syndrome commonly struggle with. The chances of this happening are very low, but it is certainly not unprecedented in the history of evolution.
  - Tabular-Iceberg 3y ago
    They certainly have a good ecological niche to get started in. When I see people with Down syndrome out and about I only get more inclined to support policies that allocate resources to them. Of course this niche doesn’t exist everywhere, for example in Iceland they have a very aggressive abortion campaign against the syndrome.
- Tabular-Iceberg 3y ago
  Turns out that this already happens: https://rarediseases.info.nih.gov/diseases/12480/tetrasomy-21 https://rarediseases.info.nih.gov/diseases/12480/tetrasomy-2... The bad news is that the prognosis is even worse than for the trisomy.

im3w1l 3y ago

Given that Down Syndrome is caused by an extra chromosome, I'm kinda curious how that would be inherited. Like if you have two people with Down's would there be a possibility of offspring with an extra chromosome pair? Could that in the long term lead to speciation? Would it be possible that only one of the three chromosomes is passed on from each parent, leading to a normal and healthy child?

thereticent 3y ago
It's an interesting topic. The primary cause of Down syndrome is trisomy of chromosome 21, which is what you described. That form is not inherited. A much less common cause, mosaicism, is a random occurrence during cell division and isn't inherited either. The only form that can be inherited (that we know of) is caused by translocation. Basically a piece of one chromosome can become switched with a piece of another chromosome. If no information is lost, that's a balanced translocation. Those usually still produce a normal phenotype. When the balanced translocation is passed down a generation, it can lose information or pick up extra information and become unbalanced. If the extra information is from chromosome 21, that can become Down syndrome. That's a simplistic explanation, but should do the job.
- im3w1l 3y ago
  Right that makes sense. I guess what happens in all of these scenarios is having an extra copy of one particular gene, causes it to become overexpressed, which in turn leads to all these issues?
  - thereticent 3y ago
    It's actually many, many genes that are overexpressed and result in the Down syndrome phenotype. My work is with adults with DS and Alzheimer disease--in this case, triplication of the amyloid precursor protein (APP) gene on chromosome 21 nearly guarantees accelerated development of cerebral amyloid deposition compared to typically developing people. But that's just a miniscule part of the Down syndrome phenotype.
- thereticent 3y ago
  It's actually many, many genes that are overexpressed and result in the Down syndrome phenotype. My work is with adults with DS and Alzheimer disease--in this case, triplication of the amyloid precursor protein (APP) gene on chromosome 21 nearly guarantees accelerated development of cerebral amyloid deposition compared to typically developing people. But that's just a miniscule part of the Down syndrome phenotype.
RoyalHenOil 3y ago
>Like if you have two people with Down's would there be a possibility of offspring with an extra chromosome pair? Could that in the long term lead to speciation? A similar phenomenon is common in plants. While humans have two copies of DNA, one from each parent, many plants contribute more than one copy of DNA to their offspring, resulting in plants with many more than just two copies of DNA. The number of copies a plant has can vary within the same species. Notably, domesticated plants often have more copies of their DNA than their wild counterparts have, yet they are still reproductively compatible. In animals like us, multiple copies of DNA, or even just of individual chromosomes, are much more risky, which is why it's so rare (those embryos are typically nonviable). However, different animal species do often have different numbers of chromosomes, which does provide a pathway to evolutionary divergence and speciation. Typically, species with different numbers cannot reproduce (e.g., humans and chimps), and when they can, the result is often sterile (e.g., horses and donkeys). There are several ways that species can gain or lose new chromosomes as they evolve, and you are right: duplication of an existing chromosome is one of them, although pretty rare because it often leads to serious health problems or sterility. (More common is the splitting of a chromosome or the fusing of two chromosomes, since these preserve all the genes without duplication. Another possibility is the total deletion of a chromosome, but this is extremely rare because it typically kills the embryo.) So yes, theoretically, fertile men with trisomy 21 Down's syndrome (they are usually sterile, but there have been exceptions) and women with trisomy 21 Down's syndrome could get together and start a new hominid branch. Over time, the twin chromosomes would undergo selection and diverge from one another, likely in a way that would improve on the general health and fertility issues that people with this syndrome commonly struggle with. The chances of this happening are very low, but it is certainly not unprecedented in the history of evolution.
- Tabular-Iceberg 3y ago
  They certainly have a good ecological niche to get started in. When I see people with Down syndrome out and about I only get more inclined to support policies that allocate resources to them. Of course this niche doesn’t exist everywhere, for example in Iceland they have a very aggressive abortion campaign against the syndrome.
Tabular-Iceberg 3y ago
Turns out that this already happens: https://rarediseases.info.nih.gov/diseases/12480/tetrasomy-21 https://rarediseases.info.nih.gov/diseases/12480/tetrasomy-2... The bad news is that the prognosis is even worse than for the trisomy.