Can you have Huntington's disease if no one else in your past generations have it?
-A curious adult from CaliforniaSeptember 2, 2010
Yes, you can. This surprises a lot of people because Huntington's disease (HD) is what is called a dominant genetic disease. What this usually means is that a child only has a chance of getting a disease like this if a parent has it too. But parents without HD can have a child with HD.
This is true of any dominant genetic disease. Nothing in genetics is 100% and there are always exceptions to every rule. HD is different because it breaks this particular rule a lot more than most dominant diseases.
One simple explanation is if the parents die before any symptoms appear. HD is a disease that strikes later in life. So, in this case it would look like the child got the disease even though neither parent had it.
Of course one of the parents in this case really did have HD. But there are cases where a parent really doesn't have the disease and a child does.
This has a lot to do with the fact that DNA isn't as stable as most people think. It can and does change. And the gene that is involved in HD, the huntingtin gene, is more unstable than most.
It also has to do with the fact that sometimes the same version of a gene can have different effects in different people. Sometimes such a gene version causes HD in one person but not another.
The Same but Different
As you probably know, you get a genetic disease because of the genes you have. But it is a bit more complicated than that.
See, we all have pretty much the same set of genes. That is what makes us each human.
What makes us different is that we have different versions of some of these genes. So I have blue eyes because I have the blue version of an eye color gene that we all share. You might have brown eyes because you have the brown version of that same gene.
These are the nerve cells affected by HD.
Same thing with Huntington's disease (HD). One person might not have HD because of the version of the huntingtin gene he or she has. And another person might have HD because he or she has a different version of this same gene.
But HD gets even more complicated than this. There are some versions of the huntingtin gene that can cause HD in one person but not in another.
Let's imagine that dad has one of these huntingtin gene versions that is in a gray zone. He happens not to get HD with this gene version. But his kids might if they inherit it.
Geneticists have given this a typically pretty name -- incomplete penetrance. So this is an easy way for a child to end up with HD even if neither parent has it"¦and even though this should be impossible because HD is a dominant disease.
To understand why some huntingtin gene versions are in this gray zone, we need to step back and talk about genes. And about something called CAG repeats.
Repeat After Me
Genes are basically the instructions for who we are. These instructions are written out in a simple alphabet that has only four letters -- A, G, C, and T.
As I said, these genes can come in different versions. And those different versions have to do with how the gene is spelled.
Some are just a different spelling for the same gene " like the words "grey" and "gray." A simple difference in spelling might not affect a gene's function.
But some differences are not so innocent. There are single letter changes, like a misspelling. Others are larger changes, like adding or deleting a word in a sentence. These can cause problems with how the gene works in our bodies.
The difference in the huntingtin gene that causes HD is like adding a word to a sentence. Only in HD lots of the same word " CAG " are added to the sentence.
We call this a trinucleotide repeat expansion. All these extra "words" make the DNA hard to read and the gene stops working correctly. And when the huntingtin gene stops working, you eventually end up with HD.
This string of CAG's is also another reason that someone can have HD even if no one in his or her family has been diagnosed with the disease"¦yet. Let me explain.
It is normal to have some extra copies of CAG in the huntingtin gene. In fact, you can have up to 35 copies and that is normal.
People that have 36-39 copies are in the gray zone I talked about. They may or may not have HD. For example, some people with 36 copies will have symptoms of HD and other people with 39 copies will not. Again, this is called incomplete penetrance.
However, the more copies you have, the greater your chance of having the condition. When you have over 40, it is almost certain you will have symptoms of HD. We call this complete penetrance.
So how does someone get more than 40 copies? It is because these CAG repeats make the huntingtin gene unstable. And this gives us another reason parents without HD can have a child with the disease.
Not Written in Stone
Our genetic information is not written in stone.
People think about genes as being passed down generation after generation, unchanged. But this is not the case. Genes can and do change.
Sometimes something in the environment can change one of your genes. This is how sunlight can cause skin cancer. Or one of the ways that cigarette smoke can cause lung cancer. To read more about how the environment can have an effect on your genes, click here.
Another way that genes can change is when our cells make a mistake. Every time a cell makes a new copy of itself, it needs to copy all of its DNA. Cells are very good at this but sometimes a mistake slips through. If the mistake is in the wrong place, then you can end up with a disease.
Some genes are more prone to mistakes than other ones. The huntingtin gene is one of these and its CAG repeats are the reason.
Turns out that the extra CAG's can make a gene very unstable. If there are lots of extra repeats, it is easy to make mistakes when the DNA is copying itself (see video below).
Instead of copying the same number of CAG repeats, more are added. These are passed on to the next generation. This is especially true when the repeat expansion was originally in someone's dad and has to do with how sperm are formed.
This is why people with 27-35 copies of the CAG repeat in their huntingtin gene do not have HD but have a greater chance of having a child with HD. Because their 27-35 copies can increase to 36, 40, or more in a single generation.
Diagnosis and the Family
Huntington's disease (HD) can be devastating for a family. It is difficult to watch a loved one lose control of their body and their thoughts. But scientists are working hard to find ways to treat the disease.
There is genetic testing for HD. From a small blood sample, someone can find out how many CAG repeats they have. Even before they have symptoms.
But genetic testing can't tell someone when they will start to have symptoms. It can't tell them how severe their disease will be. And it can't tell them how fast the disease will get worse.
Genetic testing can be very helpful. For some people, it will reduce the anxiety of not knowing. Others will use the results for both family planning and financial planning.
Others will not want to have any part of it.
People need to carefully consider genetic testing. Both positive and negative test results can have an impact. That impact can reach far beyond the person who had their blood drawn for the genetic test.
Nice (if a bit technical) animation of how you can get extra repeats when your DNA is copied.Ellyn Farrelly
This project was supported by the Department of Genetics, Stanford School of Medicine. Its content is solely the responsibility of the authors and does not necessarily represent the official views of Stanford University or the Department of Genetics.