There are so many different kinds of genetic mutations. So far, we’ve only discussed small single nucleotide changes and insertions and deletions. But entire pieces of chromosomes can also be rearranged in what’s called a translocation. The prefix “trans” shows up a lot in science. It comes from Latin and means “across” or “on the opposite side”. “location” is physically talking about the chromosomal location. So “translocation” mean s pieces of chromosomes moving to another location.
You can think of it as two different pieces of DNA that aren’t usually right next to each other, being put next to each other. Kind of like a centaur – the top of a human attached to the bottom of the horse – a human/horse translocation. Of course, in the case of chromosome, genes or regulatory pieces of DNA are moved next to each other, and although it may not seem nearly as dramatic as a centaur, the effects can be just as surprising.
One example of a translocation that has dramatic consequences is the translocation that causes the blood cancer Chronic Myelogenous Leukemia (abbreviated as CML). In this case, part of Chromosome 9 and part of Chromosome 22 break off and swap. So now, Chromosome 9 has part of chromosome 22 attached, and vice versa. The part of chromosome 22 and the broken off part of chromosome 9 are called the Philadelphia chromosome, and this is what causes the leukemia.
But how? We imagine that Chromosome 9 and Chromosome 22 are both train tracks. On those train tracks are trains that can either be going or not going depending on the upstream signals. On Chromosome 22 there is a green signal that is stuck at green so the train is always going. On Chromosome 9, there is a more sensitive signal – some times it’s green, but most of the time it’s red so the train isn’t going.
What happens now is that there is a switch (or a translocation) that attaches the Chromosome 9 and 22 train tracks together. But when it does this, the green signal from Chromosome track 22 is telling the train on the chromosome 9 track to go – even though it usually doesn’t always go. This is nearly exactly what happens in the case of the Philadelphia chromosome, except the trains are genes that are making protein (if the signal is green) or are not made into protein (if the signal is red). The signals are parts of DNA that regulate the “expression” of the gene (in other words, whether or not the gene makes the protein).
In the case of the translocation in CML, what happens is a gene of Chromosome 22, called BCR is attached to part of the Abl gene on chromosome 9. In this configuration, the BCR-Abl fusion gene makes a protein that is always “on”. What does this protein do? Essentially, it tells the blood cells to keep growing and dividing. This makes too many blood cells and causes leukemia.
There are many different chromosomal translocations that cause a number of different diseases, but what they have in common is either creating a protein that is always on or changing the upstream signal that tells a gene to make more protein. Most of the time, this results in signalling the cell to keep growing and dividing, which is why translocations are often associated as a cause of cancer.