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I've always been curious if genetic diseases are not only heritable but also spontaneously generated. If two genes combine to produce a genetic disorder and you

I've always been curious if genetic diseases are not only heritable but also spontaneously generated. If two genes combine to produce a genetic disorder and you remove those two genes from the population does that really remove the possibility for that disease or does it reduce the probability to a very low number? I guess if you screen every embryo it wouldn't matter how they developed the bad gene they'd terminate that life anyways.

gwern 9y ago
> I've always been curious if genetic diseases are not only heritable but also spontaneously generated. They certainly are. Consider Down's syndrome: almost no one with Down's reproduces because it is a physically/socially crippling disorder. If Down's was not spontaneously generated, with considerable probability, it would not be an issue because it would've disappeared within a generation or two at most. This applies to a lot of genetic diseases: they are 'de novo mutations', not inherited, because they are sufficiently harmful that their sufferers do not reproduce for there to be anyone to inherit the disease. This is why you hear of so many recessive genetic disorders: being recessive means it won't usually have any fitness effect, so it has a chance of persisting for a long time, only occasionally hurting or killing someone. (Brand new mutations are quite common in humans on an absolute basis: I think the estimate is ~70 per person. It would be even higher except that many of them are so fatal that the sperm or egg or embryo spontaneously abort or die along the way.) There are many thousands of distinct genetic disorders, some of which can be caused by many different mutations, cumulatively affecting something like 1% of births. How specific the mutations have to be is the 'mutational cross-section' of the disease. For example, intellectual disabilities can be caused by just about anything, and the genetic cause has to be diagnosed by whole-genome sequencing of parents/child to find the new mutations and try to guess which one is responsible. > does it reduce the probability to a very low number? Yes. Unless you made everyone do IVF PGD, there will always be a 1-in-thousands chance of this or that genetic disorder, along with the ones popping up from two carriers mating. The only reason Down's is disappearing is because most of the affected fetuses are being constantly aborted, but this is not affecting the root cause (increasing maternal age) and so it will be a problem indefinitely.
- GordonS 9y ago
  > almost no one with Down's reproduces because it is a physically/socially crippling disorder People with Down's are almost always infertile. Regarding how 'crippling' it is, it actually varies dramatically. Down's is associated with a whole host of additional physical and mental issues, such as heart problems, sleep apnea, low muscle tone, behavioural issues, autism and dementia. But not everyone with Down's has all of these issues, and the severity of them varies. IQ levels so vary greatly. Even the degree of facial features typically associated with Down's varies - for some people with Down's(especially children) it would not be immediately obvious to others, if they could tell at all. How societies deal with people with Down's has also changed greatly over the past few decades. In most Western countries a lot of help is now available (speech and language therapy, occupational therapy etc), and life expectancy, prospects and opportunities for people with Down's have all increased.

gwern 9y ago

> I've always been curious if genetic diseases are not only heritable but also spontaneously generated. They certainly are. Consider Down's syndrome: almost no one with Down's reproduces because it is a physically/socially crippling disorder. If Down's was not spontaneously generated, with considerable probability, it would not be an issue because it would've disappeared within a generation or two at most. This applies to a lot of genetic diseases: they are 'de novo mutations', not inherited, because they are sufficiently harmful that their sufferers do not reproduce for there to be anyone to inherit the disease. This is why you hear of so many recessive genetic disorders: being recessive means it won't usually have any fitness effect, so it has a chance of persisting for a long time, only occasionally hurting or killing someone. (Brand new mutations are quite common in humans on an absolute basis: I think the estimate is ~70 per person. It would be even higher except that many of them are so fatal that the sperm or egg or embryo spontaneously abort or die along the way.) There are many thousands of distinct genetic disorders, some of which can be caused by many different mutations, cumulatively affecting something like 1% of births. How specific the mutations have to be is the 'mutational cross-section' of the disease. For example, intellectual disabilities can be caused by just about anything, and the genetic cause has to be diagnosed by whole-genome sequencing of parents/child to find the new mutations and try to guess which one is responsible. > does it reduce the probability to a very low number? Yes. Unless you made everyone do IVF PGD, there will always be a 1-in-thousands chance of this or that genetic disorder, along with the ones popping up from two carriers mating. The only reason Down's is disappearing is because most of the affected fetuses are being constantly aborted, but this is not affecting the root cause (increasing maternal age) and so it will be a problem indefinitely.

GordonS 9y ago
> almost no one with Down's reproduces because it is a physically/socially crippling disorder People with Down's are almost always infertile. Regarding how 'crippling' it is, it actually varies dramatically. Down's is associated with a whole host of additional physical and mental issues, such as heart problems, sleep apnea, low muscle tone, behavioural issues, autism and dementia. But not everyone with Down's has all of these issues, and the severity of them varies. IQ levels so vary greatly. Even the degree of facial features typically associated with Down's varies - for some people with Down's(especially children) it would not be immediately obvious to others, if they could tell at all. How societies deal with people with Down's has also changed greatly over the past few decades. In most Western countries a lot of help is now available (speech and language therapy, occupational therapy etc), and life expectancy, prospects and opportunities for people with Down's have all increased.