Question about mutations and disease

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A question about mutation build up in cells.
I'm hoping a mod can move this to the biology forum section, I keep trying to post in it, but every time I click on the biology forums I'm automatically logged out.

I've read about how sometimes the DNA polymerase inserts a wrong amino acid and ends up modifying the DNA rather than the RNA, which leads to a permanent mutation. I also read that DNA polymerase makes a mistake 1 for every 1 billion base pairs. If our DNA has over 3 billion base pairs, and we get millions of new cells a day, what stops these mutations from building up to a point where our body is no longer able to function.

What's to stop someone from spontaneously developing sickle cell anemia or some other genetic disease due to random mutation build up.
 

DaveC426913

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Any individual cell getting mutated will not generally be propagated to the rest of the body , especially since cells die and are replaced (from cells without that spontaneous mutation).

The mutations that are of concern are the ones that are in the sex cells - the sperm or ovum. These ones
are the source for all other cells in the developing organism, so a mutation that's made it into the zygote will be propagated throughout the organism, resulting in, say, anemia.

I'm not a biologist. See tagline*.
 
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Any individual cell getting mutated will not generally be propagated to the rest of the body , especially since cells die and are replaced (from cells without that spontaneous mutation).
What about the mutations that occur in stem cells, won't those eventually build up?
 

pinball1970

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Summary: A question about mutation build up in cells.

I'm hoping a mod can move this to the biology forum section, I keep trying to post in it, but every time I click on the biology forums I'm automatically logged out.

I've read about how sometimes the DNA polymerase inserts a wrong amino acid and ends up modifying the DNA rather than the RNA, which leads to a permanent mutation. I also read that DNA polymerase makes a mistake 1 for every 1 billion base pairs. If our DNA has over 3 billion base pairs, and we get millions of new cells a day, what stops these mutations from building up to a point where our body is no longer able to function.

What's to stop someone from spontaneously developing sickle cell anemia or some other genetic disease due to random mutation build up.
These can build up, that is what disease is. The immune system is constantly mopping up rogue cells not just pathogens.
Remember that most mutations are neutral and do not affect function. some mutations can result in cell death, apoptosis so that's as far as that mutation goes. If a cell avoids apoptosis and or recognition by the immune system after mutation then that can lead to disease.
Anaemia is a good example actually, see aplastic anaemia.
Chloramphenicol is a powerful anti biotic that is usually only administered in hospital due to the risk of aplastic anaemia.
 

pinball1970

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What about the mutations that occur in stem cells, won't those eventually build up?
This on stem cell mutations
This mentions location rather than the number of mutations being relevant.
 

Ygggdrasil

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I've read about how sometimes the DNA polymerase inserts a wrong amino acid and ends up modifying the DNA rather than the RNA, which leads to a permanent mutation.
DNA is composed of nucleotide base pairs, so a mutation would occur when DNA polymerase adds the wrong nucleotide. Proteins are composed of amino acids.

I also read that DNA polymerase makes a mistake 1 for every 1 billion base pairs. If our DNA has over 3 billion base pairs, and we get millions of new cells a day, what stops these mutations from building up to a point where our body is no longer able to function.
A few points to note here:
1) While the human genome is composed of ~3 billion base pairs, not all of these are required for proper function. Only about 2% of the human genome codes for protein, and ~10-20% is evolutionarily conserved. >50% of the human genome is composed of repeat elements derived from things like ancient retroviruses that inserted into the our genomes many millions of years ago. Furthermore, even among functional regions of the genome, not all regions are required in all cell types. Some genes are required only during certain phases of development. For example, the human genome encodes a gene for fetal hemoglobin which is required only for fetuses. Mutation in this gene in an adult would not have any major effects (unless they occur in germ cells, see below). Similarly, mutation of a gene required only in the brain would not have an effect if the mutation were to occur in a cell elsewhere in the body.

2) As others in the thread have mentioned, mutations in individual cells are not a huge problem. Organs are composed of many cells, so if some number are not functional due to mutation, others cell in the organ can still function and pick up the slack.

3) Mutations during DNA replication can sometimes, however, cause problems like cancer when mutations inactivate tumor suppressor genes and activate oncogenes that cause cell to start growing out of control. In fact, some scientists argue that the mutations that occur during DNA replication in stem cells account for a large fraction of cancers (others argue that mutation related to environmental exposures like UV radiation, smoking or diet are more important, see https://www.physicsforums.com/insights/causes-cancer-bad-luck-bad-lifestyles/ for a discussion). However, there are various cellular mechanisms that try to prevent this from happening. The cell has various quality control pathways to help recognize DNA damage and prevent cells containing DNA damage from dividing. For example, the protein p53 (sometimes referred to as the "guardian of the genome") will stop cells containing DNA damage from dividing until either the cell can fix the damage, and if the damage cannot be fixed, p53 will help activate the programmed cell death (apoptosis) to permanently remove the cell (for these reasons, most tumors have mutations in p53 as they need to first inactivate this protein before they can accumulate more mutations to become cancerous). The immune system also has the capability of recognizing cells with extensive mutations, and can help to remove these cells as well (which form the basis for the new cancer immunotherapy approaches in oncology).

4) As others have mentioned, avoiding mutation in cell that will become gametes is especially important, because these cells need to have the capability of forming all tissues in the human body. Mutations in these cells can cause genetic diseases in one's offspring. As such, the body employs special mechanisms to minimize the number of cell divisions of germ cells (indeed, they are separated from the rest of the cells in the body very early on during embryonic development) and have much more rigorous DNA repair and quality control checks at various stages of gametogenesis. Here's a good resource discussing mutation rates per generation and relating that to the number of cell division steps during gamete formation: http://book.bionumbers.org/what-is-the-mutation-rate-during-genome-replication/

Of course this process is not perfect, so some gametes do go on to have very serious mutations. This is part of the reason why 30-50% of all fertilized eggs are eventually miscarried.
 

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