Geneticists really need to work on naming their genes. Drosophila geneticists are the worst - we give genes names such as Grunge, grim reaper, and swiss cheese (see a great link here), but sometimes the human geneticists can slip as well. One example - the fragile X syndrome. The name fragile X suggests that this version of the X chromosome is like a Ming vase...delicate and susceptible to fragmenting. But in reality, it causes a much worse condition.
What happens in fragile X is that there has been a duplication in a portion of the DNA on the X chromosome. Duplications happen all of the time, but unfortunately, this one happens to occur within the coding region for a gene. This gene is FMR-1, and it appears to be a very important gene for humans. FMR-1's gene product, the fragile X mental retardation protein (FMRP)is responsible for development of the neurons - the cells that conduct billions of electronic messages in our bodies, and brains, per second. In the mutated form of FMRP, there has been a repeat in one of the instructions, commonly called a codon. The repeat, called a trinucleotide repeat since it adds three new "letters" to the DNA message, causes the resulting protein to fold incorrectly. Proteins are all about folding, it is their three-dimensional shape that gives them their unique function. Imagine if you needed a wrench for a certain repair job, and the manufacturer mistakenly bent the top of the wrench at a 45 degree angle... it would make it very difficult to complete the task at hand. Proteins operate in much the same manner.
Another interesting aspect of repeats is the fact that they have the ability to increase in size from generation to generation. During the production of egg and sperm cells in humans (called meiosis), similar chromosomes line up with one another. The repeats can cause a misalignment, which can increase the size of the repeat. More repeats means a more severe form of the disorder. That is why everyone with fragile X does not have the same symptoms (what us geneticists call a phenotype).
Since Fragile X is on one of the sex-chromosomes, males (who are XY) are definitely more susceptible to its effects, since females (XX) at least have the chance to have a second, good copy of the chromosome. Fragile X syndrome can result in both mental retardation and a form of autism. In fact the recent attention to autism has resulted in some interesting discoveries about fragile X, specifically its relationship with a group of receptors on the cells in the brain called mGluR5. Identification of a receptor is a big deal, since drugs can be developed to interact directly with the receptor. Individuals with fragile-X also sometimes display aggressive behavior, but that is most likely believed to be a secondary result of the disease, probably brought on by speech difficulties, frustration, and anxiety - complications of the effects of mental retardation.
While drug studies are promising, a "repair" of fragile X is unlikely. Since the repeats in fragile X can be very large (200+ copies sometimes) it is unlikely, at least in 2008, that the defect could be repaired using any form of biotechnology, including gene therapy. Furthermore, since the gene product, FMRP, has already caused problems in the cells, it would probably not be possible to reverse the influence on the person. We should be able to treat the symptoms, and it appears that we are getting better at understanding how to do this, but this may be a good example of where our genetic limitation lie.
No comments:
Post a Comment