(PSYCHIATRIC TIMES) - I experienced an interesting confluence of events the other day. My 11-year-old son has been finding out about the great power of online information. Although we limit his access to assistance with homework, he is already a digital whiz kid who knows where to find a great deal of information for writing tomes like Norse history reports. In my day, it would have taken an entire afternoon of digging through texts at a university library to obtain items he found in a few seconds.
The confluence came about because of what I was doing while sitting next to him. While he was Headshotbusy downloading information about Vikings, I was reading an update on a story that I have been following for a few years: the attempt to create a simple, objective blood test that could properly identify mood disorders. That would be a truly handy gadget for mental health professionals to have in their diagnostic tool kits! Going through the literature, which relies heavily on gene expression data, it hit me how profoundly the judicious use of online databases has contributed to the scientific rigor of the research. The Internet was not only seminal to my son’s work but also to this blood test research.
In this column, I will discuss new progress on this Internet-boosted line of inquiry. I will begin with a few basics about differential gene expression and microarrays and will then move on to something that researchers are calling “convergent functional genomics.” As you shall see, the clever use of online databases both confirmed and extended the work done at the bench. As a result, it may very well be possible in the next few years to have a clinic-ready blood test that is capable of diagnosing unipolar and bipolar depression. There may even be a diagnostic test for schizophrenia.
In order to understand this promising research, we first need to review a few facts about differential gene expression, microarrays, and their use in the laboratory. As you may remember, only about 2% of the genome encodes for messenger RNA (mRNA)—sequences usually referred to as class II genes (the rest of the genes encode either ribosomal RNA, called class I genes, or transfer RNA, called class III genes).
You can subdivide class II genes into 2 categories based on the transcriptional activity. Some class II genes are turned on all the time; we often refer to them as “housekeeping” sequences. Some class II genes are expressed quite cell-specifically (a neuron has a very different job description from, say, a gut fibroblast, after all), and they are either completely silent or are called on infrequently, depending on the needs of the cell.
Researchers can capture these “need-specific” class II mRNAs quite easily because of the binding properties of their nucleotides. Consider this example: Suppose you are interested in finding out which neural genes, if any, become activated in the presence of a test medication. You take 2 groups of cells; 1 group will not be exposed to the drug (serving as the unstimulated control), while the other will be exposed to the drug for a set period.
How do you get the medication-specific genes? You simply isolate both sets of mRNA, convert them to helical DNA, and then mix them together. The genes that are commonly expressed in both populations (like those housekeeping genes) will find each other and, with some coaxing, bind together. This makes them double-stranded. The genes that are unique to the medication stimulation have no “partners” and will not bind to anything. This makes them single-stranded.
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