Tanya Eble, M.S.
Baylor College of Medicine
Our bodies function using the genetic instructions that we receive from each of our parents. These genetic instructions are found inside each of our cells, which are the basic units of life in our bodies. (Cells make up the tissues, and tissues make up the organs of our bodies.)
The genetic instructions that tell our bodies how to grow and how to work are packed into string-like structures called chromosomes (pictured below).
Chromosome photographs (karyotypes) contributed by
Kleberg Cytogenetics Laboratory, Baylor College of Medicine.
There are 46 of these chromosomes in each of our cells. You can see in the pictures above that the chromosomes are grouped into pairs of two. In each pair, one chromosome was received from the mother and the other was received from the father. In this way, a person inherits half of their genetic instructions from each parent. Just as we receive one whole chromosome from each parent, we also receive one copy of each instruction from each parent. These instructions are called genes.
When you look at the pictures of the chromosomes above, you see that there are 22 numbered pairs of chromosomes. There is also a pair labeled either XX or XY. The numbered pairs are called autosomes. The X and Y are the sex chromosomes and determine if a person will be a boy/male (XY) or girl/female (XX).
When a gene is missing, it is comparable to a page being torn out of the book. All the information (letters) on that page is lost.
The building blocks of DNA, the genetic code, can be compared to the letters on the page. If a letter is missing or extra, or changed into another letter, the information in the text is incorrect and cannot be read properly. Below you see a change in the word “gene”. The letter E is missing, and the correct meaning is lost. This is comparable to what happens when there is a mutation, or a change, in a gene. The body reads and follows that
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Think about this comparison of chromosomes and encyclopedias. People organize the information in an encyclopedia alphabetically just like we organize chromosomes in pairs. Thinking about the autosomes (chromosomes number 1 to 22), the non-sex chromosomes, we know that just as a person receives one chromosome in each numbered pair from each parent, they also receive one copy of every gene on these chromosomes from each parent, so that we have two copies of all of those genes.
This is different for the X and Y chromosomes. The Y chromosome is smaller than the X chromosome and unlike with the autosomes, not all of the genes found on the X are also found on the Y. Some genetic instructions come only from the X chromosome and there is no second copy of the gene on the Y chromosome. Therefore, boys only have one copy of most of the genes that are located on the X chromosome. Because girls have two X chromosomes they have two copies of the genes that are located on the X chromosome.
Girls’ bodies compensate for having two X chromosomes by “turning off” one X chromosome in each cell. This process of turning off an X is called X-inactivation and the X that is turned off is called the inactive X.
| [inline:fig3_a.jpg] | There are two X chromosomes in this cell. One labeled blue and the other red. |
| [inline:fig3_c.jpg] | The cell divides so that first there are two and then four cells, each cell with one red and one blue X. Eventually, one X in each cell is inactivated. |
| [inline:fig3_d.jpg] | The active X is underlined. For each cell, it is completely random which X is inactivated. |
| [inline:fig3_e.jpg] | However, once it is done, it remains the same X that is inactivated. (The cells are now color labeled. The blue cells are those in which the blue X is active and the red cells are those in which the red X is inactive. |
| [inline:fig3_f.jpg] | For the body to grow and develop, cells have to divide many times. After a cell has divided, the same X will remain inactive, and a person ends up with a mixture of cells, some of which have the red X inactivated and others that have the blue X inactivated. |
Cells only use the gene instructions that are active. If an X has been “turned off” our bodies do not use the genes on that chromosome. Normally, X-inactivation is random, meaning that in each of our cells the two X’s have an equal chance of being inactivated. However, once inactivation occurs, that X cannot be turned on again. Normally about 50% of cells have one X active and 50% have the other X active, but sometimes this varies, and more cells have for example the blue X active. This is called skewed X inactivation.
For individuals who have two working copies of each gene on the X chromosome, it does not matter which chromosome is turned off. However, when one copy of a gene known to cause health problems is non-working , the choice of which X is active becomes more important. If the X with the working copy of this gene is turned off in more cells than the X with the non-working copy, the person will have more severe health problems. Sometimes, the cells that have the X with the non-working copy do not grow or divide as well and the body will end up with more cells that have the X with the working copy active.
This type of skewed X inactivation is sometimes seen in disorders that are caused by problems with a gene on the X chromosome. Some researchers have found evidence for this type of skewed X inactivation in girls with Aicardi syndrome but not all scientists agree.
Dr. Van den Veyver’s lab is currently studying X inactivation as part of their Aicardi syndrome research.
Other commonly asked questions about the genetics of Aicardi syndrome:
Is Aicardi syndrome inherited?
A genetic disease is any disease that occurs due to a change in a person’s genes. We believe that Aicardi syndrome is a genetic disease. But this does not mean it is inherited. Not all genetic diseases are inherited. When a disease is inherited it means that it is passed through the family from parent to child.
We do not think that Aicardi syndrome is inherited. Currently, we believe that girls with Aicardi syndrome have what is a called a de novo genetic change or de novo mutation. This means the non-working gene is new in them and the gene was working in their parents.
Why do we think Aicardi syndrome is due to a non-working gene on the X chromosome?
When a disease-related gene is located on an autosome (chromosomes number 1 to 22) we see equal numbers of affected boys and girls. This is not the case with Aicardi syndrome as it is seen predominantly in girls. As far as we currently know, only boys with an extra X chromosome (2 X’s and a Y) can have Aicardi syndrome. We suspect that boys who have 1 X and 1 Y and a non-working Aicardi gene do not survive to birth.
How likely is it that I will have a second child with Aicardi syndrome?
It is very unlikely. There has only been one report from the 1980’s of sisters who were both affected with Aicardi syndrome. We believe Aicardi syndrome is “sporadic” and happens by a new genetic change (de novo mutation) in one particular gene. The chance for this to happen twice at the same gene in one family is very small.
Is there a blood test for Aicardi syndrome?
Aicardi syndrome is currently diagnosed by clinical examination, not by a blood test. Once a gene is identified it may become possible to confirm a diagnosis of Aicardi syndrome by looking for the associated genetic change.
How can I learn more about participating in Aicardi syndrome research?
For the research group at Baylor College of Medicine: Contact Dr. Ignatia Van den Veyver, the Principal Investigator (iveyver@bcm.edu phone: 713-798-4914)) or Tanya Eble, the Study Coordinator (teble@bcm.edu phone: 713-873-2290). We are always happy to hear from you and answer questions.
For the research group at the University of California, San Francisco, visit their
web page.
A listing of all Aicardi syndrome research projects underway can be
found here.