|
We are often asked what is the most amazing thing we discovered. Wow. That makes it sound as it there was some sort of eureka moment when suddenly we discovered something no one else knew before. This is just not how science works. Even if you have a flash of insight, it then takes months or years to prove it to be accurate. In reality, science moves incrementally, building upon one small step after another, slowly evolving to new understanding. And when the goal is to make the chromsome18 conditions treatable, that goal is so massive a goal that it is sometimes hard to recognize progress. In reflecting on the big observations that we have learned over these last 30-plus years three things come to mind.
1. Everyone has chromosome abnormalities.
Every one of us has multiple deletions and duplications of sections of our chromosomes. Most are very small and in between genes. But many are larger and most people have one large enough to include a gene. These types of chromosome changes are so common that most conceptions are chromosomally abnormal and are miscarried before the pregnancy is even detected. Most of the recognized pregnancies that are miscarried early are also chromosomally abnormal. People with chromosome 18 conditions are not unusual because they have a chromosome deletion or duplication. They are unusual because their chromosome change is one that is survivable to birth.
2. Gene function is no clue
One of our goals is to determine which chromosome 18 genes have products that are involved in bodily functions affected by too few or too many gene copies. These are called dosage sensitive genes. We observed that the apparent importance of the bodily process is no clue as to whether a genes is dosage sensitive or not. For example, an important gene for early brain development may perform its function normally if there is only one copy of the gene or if there are extra copies of the gene. By the same token, a gene that at first glance looks like it is involved in a mundane housekeeping function may turn out to be the rate limiting step is a very important process. If you should hear about a gene that is important to some aspect of health that seems related to a problem people with a chromosome 18 condition have, that information does not imply the gene is dosage sensitive and relevant to the chromosome 18 condition.
3. Only 10% are dosage sensitive
Although we have hypothesized this for many years, that only 10% of the genes will be dosage sensitive, we are finally able to conclude that this hypothesis is accurate. The data supporting this hypothesis comes from decades of medical research as well as our own studies. This means that of the 263 genes on chromosome 18 only about 26 are dosage sensitive. For any one person this means that only about 4 or 5 might be the genes underlying their disability. These conditions will not be impossible to treat, just complex.
| 
