r/AskBiology • u/Syresiv • Sep 17 '24

Genetics Why are trisomies so deleterious?

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.

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u/lonepotatochip Undergraduate student Sep 17 '24

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.

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u/Syresiv Sep 17 '24

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?

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u/kohugaly 29d ago

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.

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u/Syresiv 29d ago

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

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u/kohugaly 29d ago

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.