Mixed up Chromosomes

(c) Hybrid Medical Animation

We can mix up our strings of DNA (chromosomes) in a few ways. This week, we’ll talk about translocations.

We’ve talked about the correct number of chromosomes in a karyotype and banding. To refresh, humans have 46 chromosomes or 23 pairs of chromosomes in our regular (somatic cells). Eggs have 23 chromosomes and sperm have 23 so when they pair up, we get the full chromosome complement.

A chromosome translocation is when a piece of a chromosome is found on a different chromosomes (e.g. a piece of chromosome 7 is found on the tip of chromosome 11).  You may have heard it described in fancier terms = abnormality due to rearrangement of pieces between nonhomologous chromosomes. Nonhomologous just means different chromosomes. We’ll go through the basic concepts – it’s easier than you think!

To start talking about translocations, we are going to worry about reciprocal translocations. In this case, two pieces are exchanged:

You can see that part of the black chromosome has exchanged places with part of the blue chromosomes. When the translocations are balanced (as above) meaning that all chromosome information is present but just in a new spot, it doesn’t usually cause any problems.  Because there is no outward manifestations, it is difficult to determine the frequency of people carrying balanced translocations. You may be a translocation carrier and not know it! (Note: I’ve done my chromosomes so I know any of my imperfections aren’t due to obvious translocations.)

The most common problem with carrying a translocation is difficulty having children. Because the chromosomes are a bit mixed, you can see imbalances after meiosis. We’ll go over the most common conceptions in a later post. As a preview, you can see that a gamete (egg or sperm) that received the first black chromosome and the second blue chromosome would have too much black (extra bit on the tip of the blue chromosome) and not enough blue chromosome (the tip was replaced by the extra black). Having too much or too little of our chromosomes can be a problem as discussed in Chromosome Disorders. The result of an imbalance depends on the size and the genes included in the imbalance. Clinicians have to rely on previous cases to offer any predictions and that is often hard to do.

It is theoretically possible that a translocation could split a gene and make it inactive. This could lead to very specific diseases – but it is not our main concern when we are discussing translocations. Because translocations are at the chromosome level, they impact many genes and you see a more global effect.

Of course, there is always an exception and I want to share the Philadelphia chromosome with you. This is a very specific chromosome translocation between the long arms of chromosome 9 and 22 that creates a fusion gene: the Abl1 gene on chromosome 9 comes under control of the BCR (breakpoint cluster region) of chromosome 22. The new arrangement means the gene is on all the time promoting growth even when the signals for growth aren’t there and it leads to Chronic Myelogenous Leukemia. The successful chemotherapy drug Imatinib (Gleevec/Glivec) targets the ABL portion of the BCR-ABL fusion. [One area of confusion that arises in class: the Philadelphia chromosome happens spontaneously and people are not born with every cell having this translocation. We’ll go over this more in cancer genetics but our proper development requires strict control of growth and movement so mutations promoting tumour growth would dramatically interfere with development.]

Other common questions: where do the inherited chromosome translocations come from? Do they happen in meiosis or mitosis? How do these breaks happen? For now, please don’t worry about how the breaks happen – we want to focus on the concepts of having the correct amount of information in our chromosomes. It can be in the wrong spot but we should still have 23 pairs of information.

A fancier image of a translocation between chromosome 4 and chromosome 20 (source NIH):