Bits and Genes

Recently, there have been some "breakthrough" articles regarding genetics and schizophrenia. But before I get to the details of that, a bit of background is in order.

My normal occupation is that of computer network technician. Part of my experience is with data storage which is not unlike some aspects of genetic coding. Computer information is made up of one's and zero's, lots of them to be a bit more precise. When they are stored on magnetic types of media. which is what hard disk drives are, or on things like CD-ROM's where they are little bits of reflective material, they are read by some type of reader device and reconstituted back into "reliable" strings of one's and zero's where the computer processes them according to a set of instructions contained in the computer. We see the the results on our screens and we are either happy with the results or infuriated with the lack of them.

If you have used a computer for any length of time, you have become frustrated when the bits of information get fouled up and things go wrong. I am often asked "What caused the problem?"

Far too often, there may not be a specific cause. The timing circuitry in a computer is extremely precise and the one's and zero's in the memory of the computer are represented by voltages which must be nearly constantly refreshed. If that process is subject to fallout of the proper voltages, errors can occur. There are error detection and correction systems that are used to correct for potential errors in the storage media and they have phenomenal measures of reliability. These sometimes are on the order of years of undetected and uncorrected errors. However, we must be careful to remember that if there were 300 million computers all running for one full day and we were looking at an error rate of one undetected and uncorrected error for every ten years of computing time, there would still be 82,192 undetected and uncorrected errors per day on our computers.

If you keep that number of errors in mind, consider the human genome and the billions of people on Earth and its process of replicating the genetic code. Also keep in mind that there are between 20 and 25 thousand genes in the human genome and roughly 3 billion chemical pairs that make up those genes, you can begin to see the potential for error. As a matter of fact, there are some type of errors that are of interest to researchers that have some very interesting characteristics.

As one might suspect, the potential for flaws in the genetic makeup of an individuals DNA is really quite substantial. It seems as though the genetic material is subject to errors, just like any other thing that is subject to a recreation or manufacturing process. In this process some of the genetic material can be missing and some of the material can be reproduced more than once. If some of these errors take place, they might determine either good or bad characteristics in the resulting person.

One of the first genes to be recognized as having multiple copies is the gene CCL3L1. It is of interest because " (CCL3L1), competes with HIV by binding to the protein the virus uses to enter the cell. They found HIV-positive subjects had fewer copies of CCL3L1 than HIV-negative subjects from the same geographical group: each additional copy of the CCL3L1 gene reduced the risk of HIV infection by 5-10%. Duplications of CCL3L1 not only reduced infection rates and also slowed disease progress once infected."

This explains why some people are lacking in their ability to get AIDS which is caused by HIV.

The current research as it applies to schizophrenia suggests that the number of copies of a particular gene (also known as Copy Number Variations or CNV's) had a significant impact on the presence of schizophrenia. In particular, several large scale deletions were associated with schizophrenia. Not only was this found in one study, but simultaneously in two separate independent studies. People who had these particular deletions were nearly 15 times more likely to develop schizophrenia than subjects who did not have the deletions.

This is important not in a particularly practical manner, but more so in finding a small portion of the reason why a small number of the people who suffer from the disease of schizophrenia develop the disease.

One of the problems with the application of basic research is the inability to draw generalization to wide ranges of patients who suffer from the diseases. I was present at a NAMI meeting where Dr. Aaron Janowsky of Oregon Health and Science University was describing research he was involved in that was looking at a sub-group of subjects diagnosed with schizophrenia that were split into groups that either had or did not have a reaction to Niacin. Most people diagnosed with schizophrenia do not have a Niacin reaction, which is characterized by a reddish flushing of the skin when exposed to Niacin. There is no particular conclusion to be made from this fact, other than observing that there is a strong association of a lack of Niacin reaction in those diagnosed with schizophrenia.

One of the devilish problems with research on schizophrenia is that the disease is diagnosed by behaviors and symptoms, not a specific chemical cause. In this case, there may be a disease or form of the disease which could be characterized by the lack of a Niacin reaction and a genetic deletion. But since people who do have Niacin reactions and do not have specific genetic deletions are also classified and diagnosed with schizophrenia, what are we to conclude?

The problem stems from the fact that we diagnose mental diseases in the manner in which we do, by a set of guidelines set up in the DSM-IV manual. While it is inadequate to fully describe the precise nature of mental disease, there is no other alternative to use to attempt to assess and research the aliments of mental disorders. Until then we will look toward each clue that will refine our understanding of what causes the behaviors that we outwardly observe.

Unfortunately, the disorder we call schizophrenia is most likely a series of problems with multiple causes, resulting in behaviors that have a similar outward characteristics. This would really explain why there is a wide range of effectiveness of drug treatments and such variability in the course of the disease(s). In the meantime, research continues and more and more clues are found that help explain the causes. Eventually science will gather more and more clues to this extremely complex set of disorders. Until then we will celebrate the accumulation of clues to the causes that will eventually lead to better treatment .