Posted by Viridis on April 13, 2003, at 15:20:52
In reply to Re: 'DNA chip matches AD to patient': is report true?, posted by Larry Hoover on April 13, 2003, at 8:57:46
I can't tell from the article exactly what they're testing, but in general, there are two major ways that "gene chip" technology can be used to identify the causes of disease.
One is to screen for particular mutations that are associated with the disease. As Larry points out, even if a particular genotype has been demonstrated to make people prone to depression, there still have to be studies that reveal which drugs work for people with that mutation. At this point, the genetic basis of most mental disorders (including depression) is still poorly understood. So, although the approach of testing for particular mutations and then using drugs known to treat these conditions is certainly promising, we're nowhere near that point yet, as far as I know.
The other way that "gene chips" or "DNA chips" are used (and this is what geneticists are usually talking about when they refer to this technology) is to screen for expression of particular genes. "Expression" describes the extent to which the protein encoded by a particular gene is actually produced by cells. DNA carries the information for making a protein, but then there are several steps required to make the protein. First an RNA complement of the DNA has to be made (transcribed), then this "messenger RNA" goes out of the cell nucleus to places in the cell where the information is translated into the amino acid "language" of proteins.
Gene expression can be altered by genetic and environmental factors. For example (see link below) trauma or chronic stress can lower or raise levels of expression, even if the genes themselves aren't faulty -- or there can be an interaction between genes and environment. "Gene chips" called microarrays have many dots of DNA representing the genes of interest. If samples of total cellular RNA are applied to the chips, the messenger RNAs that are present in the cells bind to the appropriate DNA. The degree of bnding (and therefore the amount of mRNA, and therefore the amounts of different proteins being produced) can be quantified by fluorescence techniques.
Affymetrix (one of the "big guns" in gene chip research) is experimenting with ways to measure gene expression in brain cells, and is finding altered patterns of expression in certain parts of the brain in depressed patients. Here's a link:
http://www.affymetrix.com/community/wayahead/microarrays_shed_light_on_depression.affx
So, this approach could identify deficiencies that lead to depression whether they're genetically- or environmentally-based, and lead to treatments that address the problems with gene expression, either by affecting expression itself or compensating for the altered levels of certain gene products.
But, I don't think we're there yet either. Most such approaches would probably require RNA samples from brain cells (not just blood etc.), and we still have to figure out how to match the drugs to the problem.
So, while genetic technology is advancing fast, and no doubt will prove very useful for treatment of depression in the future, I think progress will be incremental. I predict that bit by bit, different mutations will be identified that predispose people to depression. At the same time, expression problems that lead to depression will gradually be unravelled. People who have particular depression-causing problems will be treated more effectively, but for others it will continue to be hit-or-miss, until the basis of their disorder is identified, a test is developed, and the appropriate meds are found.
All of this is very promising, but I really doubt that a magic chip is going to appear in the near future that will allow unambiguous choice of meds -- it's still too early in the process.
poster:Viridis
thread:218875
URL: http://www.dr-bob.org/babble/20030411/msgs/219034.html