|
An analogy is a comparison between two things. Analogies can be helpful in medicine because they allow us to visualize things that may not be visible and appreciate connections that may be difficult to conceptualize. Here are a few analogies that might help you think about some of the chromosome 18 related issues.
The brain can be thought of like a car. Likewise, your brain is a complex system composed of many parts working together to make it work properly. You might ask, which part of the car makes it go fast? Unfortunately, you can’t point to just one thing that is responsible for making a car go fast because it is a system of parts working together to ensure that the car runs at its best.
We might address that question differently by asking which parts of the car can affect how fast it can go? A “tune-up” to ensure that a car will be in good working order requires checking and potentially fixing several different things. (I won’t cite examples because the gearheads in the group will be laughing too hard to continue reading.) But the point is that it may take fixing or optimizing several things relating to how the brain functions, not just one, to help people with chromosome 18 conditions live a more independent and healthy life. Because we are not looking to identify and fix just one thing, our challenge is bigger, but it is not impossible.
When it comes to thinking about the function of all genes on chromosome 18 and their effects on people when there is a deletion or duplication, the well-tuned car analogy is also helpful. Consider the potential importance of different genes on chromosome 18 when someone has too many, or too few copies of that gene. To bring it back to our car example, imagine these genes as screws that attach the inside of the car door panel. If there is one screw that is lost, or one too many, that does not affect the function of the car.
Many genes are part of a larger system that can compensate when one component has too few or too many of a certain part. On the other hand, a screw that is part of the motor mount might not cause a problem immediately but might be a risk factor for a major problem if other parts wear out or fail. In these cases, different screws (like different genes), may look a lot alike, but their effects on function are very different.
Other car parts like the tires, for example, make the car inoperable if you have too many or too few of these parts. This list of examples could go on and on, but the idea is that in a complex system like a car--or your brain, there are redundancies and there are critical features. Our quest is to identify which are which in people and learn how to correct or prevent those that are critical to function.
_____
How big is chromosome 18?
One concept that is very hard to wrap your brain around is the size of the human genome. There are about 3 billion letters of the DNA molecule that make up the human genome.
Chromosome 18, for example, has 80,373,285 base pairs of DNA that you can think of as letters in the “Human Instruction Book” chapter that is Chromosome 18.
Chromosome 18 is one of the smallest chromosomes and includes only 3% of the total DNA that composes the entire human genome. If we were to stretch chromosome 18 out across a football field there would be 803,733 letters per yard or 22,325 letters per inch.
The largest gene on chromosome 18 (and the second largest in the whole genome) is called DCC and is 1,195,701 letters long, 53 inches, or about 1 ½ yards. One of the smallest is CHMP1B and is 3,060 letters long or about an 1/8 of an inch.
Just imagine having to read every one of those letters just for chromosome 18. A typical novel might have 500,000 letters that make up all the words of the novel. So “reading” chromosome 18 is the equivalent of reading about 160 novels, or over 5,000 novels if you include the entire human genome! This analogy is a helpful illustration to think of how amazing it is that the cells of the human body can copy this as fast as once a day.
These numbers are becoming even more relevant as we are doing DNA sequencing of the entire genome for 150 participants with chromosome 18 deletions (18p-, 18q- and Ring 18) as a part of an NIH funded study. This is A LOT of data (letters) to read, analyze and interpret.
__________
Challenges
Hopefully everyone recalls the movie, The Wizard of Oz, starring Judy Garland.
Early in the movie, while at her aunt and uncle’s farm in Kansas, Dorothy is carefully walking along the top rail of the pig-pen fence. But she loses her balance, and falls into the pig pen, and then is rescued by one of the farm hands.
Later in the movie, Dorothy and her new friends skip joyfully down the yellow brick road. These two instances of taking steps forward can be an analogy for the life led by people with chromosome 18 conditions, and how their path in life is different from typically developing children.
Typically developing children have a yellow brick road path. Obstacles appear in their path throughout life. They may veer side to side, be temporarily distracted from moving forward or even momentarily step off the path; but they jump back on the path and continue their journey undeterred, unphased and more or less on schedule.
For people with chromosome 18 conditions, so many of them go through life trying (with considerable effort) to walk along balancing on the top of the fence rail. But a gust of wind, a surprising sound, or an interesting sight can make them loose their balance and fall. It doesn’t take much to cause a loss of balance and knock them off their intended path. It is not that kids with chromosome 18 conditions cannot move forward, because they do. However, their path is narrower, and more easily disrupted by what other people may see as trivial, but for them, is monumental. Thus, it is pretty hard for the rest of us to recognize the challenges, and to seriously appreciate the strength and fortitude it takes for them to keep moving forward.
| 
