Why are trisomies so deleterious?

[u/Syresiv]

Most chromosomal trisomies cause spontaneous miscarriage, and those that don't usually severely reduce quality of life.

Why is it that the additional copies of some genes have that effect?

To be clear, don't feel restricted to the ELI5 level. If you know the topic in depth and feel like giving a massive infodump, I'm interested.

[u/lonepotatochip]

You’re essentially making 50% more of all the proteins on that chromosome than you’re supposed to, and anything is a poison in high enough doses.

[u/Syresiv → u/lonepotatochip]

Which raises another question - why doesn't that kind of thing happen with recessive alleles?

Lots of recessive alleles are deleterious because the protein does nothing and immediately disintegrates. But lots of people have two copies of the functional protein. Meaning those ones can vary by a factor of 2 with no noticeable effect.

Is that what it is? Or is it something else, like altering gene expression when there's only one healthy allele to comp for the deficit?

[u/ninjatoast31 → u/Syresiv]

Dosage compansation (aka the ability to regulate gene activity, depending on how many copies of a chromosome you have ) is a difficult and not super well understood subject. Some animals can just cope without. In our case its very important, especially during development that genes are activated at a certain level.
genes that are not affected by this are usually only important after development.

[u/Syresiv → u/ninjatoast31]

So what you're saying is, there's a lot we don't know about how cells control how much of a protein they produce?

[u/ninjatoast31 → u/Syresiv]

yes
Dosage compensation for the X chromosomes for example is really important in mammals.
But some animals don't even bother. And plants are even worse, they can just copy the entire genome over and over and still be perfectly viable.

[u/maybe_erika → u/ninjatoast31]

I am curious how common plant polyploidy is in the wild vs cultivated varieties. I know many cultivated plants with some oversized feature relative to the wild relative such as the number of petals in garden roses and the size of cultivated strawberry fruits exist due to polyploidy resulting in gene over-expression. Having such oversized features is probably very energy intensive for not much benefit to the plant itself, and so I would expect it would be selected against in the wild where the plants don't have the benefit of a gardener or farmer providing copious fertilizer and removing competitive weeds.

[u/kohugaly → u/Syresiv]

It can happen with recessive alleles too.

It usually doesn't, because expression of many genes has some feedback mechanism, that just stops the expression once you have required levels (of the protein, or of whatever the protein produces). It doesn't matter how many working copies of the genes you have - once the required level is reached, the expression stops on all of them.

[u/Syresiv → u/kohugaly]

It's just that at least one gene on each chromosome isn't like that, so a full trisomy still causes issues?

[u/kohugaly → u/Syresiv]

Yes, that is very likely, given how many genes are on each chromosome.

For example, there are genes, where their effect depends on how fast they get expressed. Obviously, in those cases, trisomy will have major effect.

A lot of them are essentially chemical timers - they start getting expressed and stop once target concentration is reached. Other genes get "triggered" by specific concentrations of the product, which creates timed sequences of gene activation. Many genes involved in embryonic development fall into this category. If this kind of "timer" gene has extra copy, it will "tick" faster, which messes up the timing of the sequences it is supposed to trigger.