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One aspect of what we do at the Chromosome 18 Clinical Research Center is to investigate and determine which genes cause consequences when all or part of the chromosome is deleted or duplicated.
Remember, a deletion changes the number of copies of the genes in the deleted region from 2 to 1. While a duplication changes the number of copies of each gene in the duplicated region from 2 to 3 for Trisomy 18, and from 2 to 4 for Tetrasomy. We call these changes in gene copy number “gene dosage” changes.
To learn about the effects of abnormal gene dosage, we gather information from our research participants and monitor the medical literature for information relevant to gene dosage effects in the general population. Every day, our team receives automatic updates from the National Library of Medicine on the 263 genes on chromosome 18. By combining data from these activities, we have determined that most genes do not negatively impact a person due to an abnormal gene dosage. This is great news because in order to correct or manage the effects of a deletion or duplication, we only have to learn to re-regulate very few genes.
Today we know that of those 263 genes on chromosome 18, 219 do not cause a problem when present in 1 copy instead of 2. There are currently only 18 genes that we don’t know enough about to determine a classification. This leaves 27 genes that may have an effect when there is only a single copy. However, from what we have seen in our participant population, only about half of those genes (13 genes) have a negative effect in less than half of the people with a deletion of that genes. This is not such a daunting number of genes to investigate!
Unfortunately, when it comes to the consequences of a chromosome 18 duplication there is much less known. There are 160 genes we think have no effect when the gene copy number is duplicated, and about 99 which there are no data with which to determine a classification. This leaves only 5 genes that are currently known to play a role where there are too many copies of that genes.
Despite major genetic research advancements in the last 15 years, there are many features of people with chromosome 18 conditions that have yet to be attributed to a specific gene but have been linked to a region of the chromosome. The responsible gene (or genes) in that region are yet to be identified. We call these “phenotype regions.”
If you want to learn about the genes on chromosome 18 that are dosage sensitive and the phenotype regions, we created a new tool to help you do that! We call it the Clinical Gene Dosage Map. The map includes only the genes that have an effect when present in an abnormal number of copies without being complicated by the large number of genes with no effect.
The dosage sensitive genes and the phenotype regions do not explain everything about someone with a chromosome 18 condition, but is another step is defining and refining the genetic basic of these conditions.
In order to use this map, you have to know the molecular coordinates of someone’s deletion or duplication which is typically called a microarray analysis. If you are unsure about how to read your report, please see this video https://youtu.be/qiMBrqj-814
To view the new Clinical Dosage Maps, begin on this page https://wp.uthscsa.edu/chromosome-18/research/. First, be sure to read the “Clinical Dosage Map Instructions” which will explain all the aspects of the map. Then, click on the “Clinical Dosage Maps” link (the final link on the page).
Many thanks to the Chromosome 18 Clinical Research Center study participants who have previewed the map and provided helpful feedback, comments, and pointed out where we all needed further guidance. However, we are still interested in your thoughts and suggestions which you can send to us using the blue “Survey Feeback” button.
Funding for this project was provided by the Cowden Foundation to the Chromosome 18 Registry and Research Society.
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