Is their limited penetrance because of evolutionary adaptation to that genetic variance? When referring to the genetic variant, how many of these variants are de novo? If it is high, then there might be evolutionary adaptation to the variant arising from de novo effects. It's not novel in evolution. Even if penetrance is low in any one generation, how about in subsequent generations? Is this all genetic load? If it is, you might really want to detect it in a generation when it is benign and look for it in their children, when it might not be. It would be an early warning across generations of a building genetic load. Again, it looks like evolutionary adaptation to the inevitable mutations occurring each generation, that inhibit normal functionality. A fault tolerance mechanism. If you were to compare the parent's and child's genome for de novo mutations, you would not be predicting disease so much as reduced functionality of the ... genome. The "polygenic score" even if there was no pathology... yet. Prediction about the future may be difficult, but it seems awfully likely that the removal of natural selection, what we call human progress, would lead to an increase in genetic load of de novo mutations, particularly ones that would be removed by the general stress of diseases. This might explain limited penetrance. It's just a normal evolutionary solution to a normal problem of heredity using DNA. @27:00 - Could the "polygenic score" represent the accumulation of de novo mutations, the genetic load? Apparently. @29:00 - They are birth defects, so to speak, but "late onset"... such as infertility or premature death. I wrote a book about all that, but if interested, try the old video about it at ruclips.net/video/wjVieFKevMk/видео.html
Is there a paper I can cite on this study, for something I am writing?
Is their limited penetrance because of evolutionary adaptation to that genetic variance? When referring to the genetic variant, how many of these variants are de novo? If it is high, then there might be evolutionary adaptation to the variant arising from de novo effects. It's not novel in evolution.
Even if penetrance is low in any one generation, how about in subsequent generations? Is this all genetic load? If it is, you might really want to detect it in a generation when it is benign and look for it in their children, when it might not be. It would be an early warning across generations of a building genetic load.
Again, it looks like evolutionary adaptation to the inevitable mutations occurring each generation, that inhibit normal functionality. A fault tolerance mechanism.
If you were to compare the parent's and child's genome for de novo mutations, you would not be predicting disease so much as reduced functionality of the ... genome. The "polygenic score" even if there was no pathology... yet.
Prediction about the future may be difficult, but it seems awfully likely that the removal of natural selection, what we call human progress, would lead to an increase in genetic load of de novo mutations, particularly ones that would be removed by the general stress of diseases. This might explain limited penetrance. It's just a normal evolutionary solution to a normal problem of heredity using DNA.
@27:00 - Could the "polygenic score" represent the accumulation of de novo mutations, the genetic load? Apparently.
@29:00 - They are birth defects, so to speak, but "late onset"... such as infertility or premature death.
I wrote a book about all that, but if interested, try the old video about it at ruclips.net/video/wjVieFKevMk/видео.html