Genetic Testing
Part 13

The science and practice of testing for Huntington's disease

What if I want to have a child that won't inherit HD?

Many people at risk for HD are worried about passing on the gene to their children. This possibility may even prevent people who deeply want children to not have any. If you or your partner are at risk for HD and want to have children who have virtually no risk of inheriting HD, now there is a way.

A recent technology called pre-implantation genetic diagnosis (PGD) can screen for genetic diseases such as Huntington's disease in fertilized ova (eggs) before they are even implanted in a woman's body. This process must be done in combination with in-vitro fertilization (IVF).

So how does all of this work? The aim of IVF is to combine the woman's eggs and the man's sperm outside of the body, in the laboratory. The first step is to collect a number of the woman's eggs. Since women usually only release one egg per month, the doctors will have to cause her to "superovulate"-that is, to develop and release many eggs at once. Superovulation is accomplished by giving hormones. Once the hormone-treated woman has many mature eggs, the doctors surgically remove them from her ovary (the organ where eggs mature). Now the eggs can be combined with the man's sperm in a laboratory dish (this is the in-vitro part). The process of a sperm joining an egg is called fertilization. Each sperm and each egg have only half the amount of genetic material, or DNA, that the rest of the body's cells have. So, when the two combine, they create one new and completely unique being. When the DNA of the man and woman combine into one cell, this is called a zygote. This single cell then begins to divide into two cells, the two cells into four cells, and so on. Once it has started to divide it is called an embryo. The next step is generally conducted at the point in development when the embryo in the lab dish consists of eight cells. The doctor carefully removes one of the eight cells for testing. Surprisingly, removing one cell at this stage is harmless to the embryo (which is to say, to date no harmful effects have been found in the resulting children). Since every cell has a complete copy of the genetic code, any one cell will suffice for genetic testing. At this point, a "genetic diagnosis" is carried out on the one cell using procedures very similar to the blood test that checks for the HD-allele in adults (for more information on adult genetic testing, click here. The testers look at the cell's DNA to find chromosome 4, where the Huntington gene is located. You will recall that whether or not an offspring will get HD depends on the number of CAG repeats in this gene. Thirty-five (35) or fewer repeats means no HD; 40 or more means that HD will eventually develop. Since no one can be sure if 36-39 repeats will result in HD, the scientists consider 36 or more repeats to mean at risk for HD. (For more information on CAG repeats, click here.) So in the case of PGD, testers will be looking to find cells with 35 or fewer repeats. They will diagnose a cell from each embryo and set aside the ones that don't have the HD-allele. They will then choose between one and four of these embryos to implant in the woman. Often, they will implant more than one embryo to increase the chances of her becoming pregnant.

Remember how we needed a collection of eggs from the same woman at the start? This procedure means that the couple will only need to go through this process once. Having a number of embryos to choose from maximizes the chances of finding at least one that is not at risk for HD. Since IVF and PGD are very expensive and physically and emotionally draining processes, neither the couple nor the doctors want to have to repeat them.

So, that is the basic process for diagnosing an embryo before it is implanted. The procedure virtually ensures that children of a PGD-tested couple will be HD-free (nothing is 100%). The process begins with IVF, in which a bunch of eggs are removed from the woman and fertilized in the lab with the man's sperm. They are then allowed to divide to the eight-cell stage. Next, PGD is done by removing one cell from each embryo. These cells are examined for the HD-allele, and embryos not containing the HD-allele are chosen to be implanted in the woman.

An interesting twist to all of this occurs when the parent at risk does not wish to be tested. PGD is an expensive and involved process to go through if you aren't even sure that you need it. But for some people the desire not to know their fate is equal to their desire to have healthy children. If an at-risk couple wishes to undergo PGD, the doctor who performs the test will inevitably find out the status of the at-risk parent. The doctor will look at cells removed from the embryos, and if any of them have the HD-allele, then the at-risk parent must also have the HD-allele. The at-risk parent will eventually develop HD. If none of the embryos have the HD-allele, then the doctor knows that the at-risk parent will not develop HD. This is a serious dilemma for the doctor. He cannot happily exclaim to the parent, "Congratulations, you don't have HD!" because then the other clients would know their statuses by default (if they weren't congratulated, they would know that this means they will develop HD). The problem is further exaggerated if the couple returns to have another child. The doctor knows that they are not at risk for HD and do not need to go through another lengthy and costly procedure to ensure a healthy child. However, again, he cannot tell them this because that would reveal to other clients their statuses by default. In order to avoid this ethical problem, clinics in the UK require that the potential parents be tested and have a positive diagnosis of HD before performing PGD. Such a diagnosis is not required in the US; however, there are doctors in the US who respect the at-risk parent's right not to know, and will do the procedure without requiring or revealing a diagnosis.

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-K. Taub, 8-10-05

For further reading:

1. Landhuis, Esther. "Pre-implantation genetic diagnosis offers hope but prompts ethical concerns." Stanford Report March 3, 2004. http://news-service.stanford.edu/news/2004/march3/invitro-33.html
   This is a non-technical article that discusses PGD in general.
2. Tassicker, R et al. "Prenatal diagnosis requests for Huntington's disease when the father is at risk and does not want to know his genetic status: clinical, legal, and ethical viewpoints." BMJ (2003); 326: 331-333. http://bmj.bmjjournals.com/cgi/content/full/326/7384/331
   This article specifically discusses PGD when the father does not want to be tested himself.
3. The Tyler Medical Clinic. Assisted Conception - Affordable Infertility Treatments. http://www.tylermedicalclinic.com/PGD.htm
   This is a good resource to learn more about PGD.

Last Modified: 10/08/2007

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