Nothing in life is perfect. Nothing in biology is either. As DNA replicates inside the nucleus, errors happen--a deletion, an insertion, a duplication, maybe an inversion of a couple bases. DNA polymerase, which copies out a new strand, is pretty good- only one in 107 bases are wrong, and with the built-in proof-reader in the very same protein, that goes down to one in 109. Not bad, not bad at all! On top of this, there are even more DNA repair proteins that routinely scan for bumps or nicks to make sure that everything is as it should be.
But sometimes, much bigger changes can happen. Deletions of entire genes, inversions of regions on the scale of kilobases (kb), translocations that cause one chromosome to attach to another! These larger structural errors are called, unsurprisingly, structural variants. As you might imagine, these are somewhat more likely to be serious enough to impair cell function, though several point mutations can be deadly as well.
But wait! Sometimes, something even worse happens: a really catastrophic nuclear event. These are called complex events (and at the far end, chromothripsis). Just look at these graphs! Each of the outer colored segments is a chromosome. One of the curves inside connects two breakpoints, where the chromosome broke and then reconnected to a different spot. In these cases, you can even see many with multiple breakpoints at multiple chromosomes!
We used to just say, "Oh, these are just one mutation happening after another, collectively creating this scrambling." But with this new data and visualization, it's clear that the breakpoints are often clustered around particular areas, which suggests a shattering of the chromosome around that point and then scrambled rearrangement. We're still not sure how this happens though.
In particular, such a catastrophic event should definitely just kill the cell, right? So why do we ever see these? The answer is that we usually don't. These are from three cancerous tumors, and tumors are where we are increasingly finding these complex variants. Do these crazy rearrangements cause cancer? Or do some cancer pathways enable the dramatic events to occur? These are the kinds of questions that some computational biologists are working to answer.
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| Some examples of DNA mutation |
We used to just say, "Oh, these are just one mutation happening after another, collectively creating this scrambling." But with this new data and visualization, it's clear that the breakpoints are often clustered around particular areas, which suggests a shattering of the chromosome around that point and then scrambled rearrangement. We're still not sure how this happens though.
In particular, such a catastrophic event should definitely just kill the cell, right? So why do we ever see these? The answer is that we usually don't. These are from three cancerous tumors, and tumors are where we are increasingly finding these complex variants. Do these crazy rearrangements cause cancer? Or do some cancer pathways enable the dramatic events to occur? These are the kinds of questions that some computational biologists are working to answer.
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