Katie: Our next question is for Mara, if two people who have HD, so they're HD positive, have a child, what is the genetic chances of that child testing positive?
Mara: I'm going to share my screen. And show a picture. Let's see, make sure I can do this the right way. So, what I'm showing you here is what we call the Punnett square. And if you think about the inheritance of Huntington's disease, it is dominantly inherited, meaning that usually, only one parent has Huntington's disease. And so the risk to the offspring is 50% for each child. We're asking a different question right now; we're asking, okay. Let's say both parents have Huntington's disease. And so on across the very top, you see a big A which is going to represent the Huntington's disease, abnormal gene. And we're going to see a little a, which is going to represent the normal copy of the gene. And then on the left side, you'll also see a big, A representing Huntington's disease gene and a little a representing, the normal copy. So it's just statistics. At this point, you look at which egg, and which sperm are going to come together, because remember we can't give all of our genetic material when we have children, we wouldn't, we're not cloning ourselves, and you only get to give half. And so the person across the top can either give the big A or the little a. The person that across on the left side can either give the big A and little a. And so you can see there are four possibilities. If you look at the top box on the left, it says AA, and that is somebody who has Huntington's disease. I'm going to let Dr. Wheelock talk a little bit more about that. Because that is a question that people ask me a lot about is what's it like if you inherit two copies of the Huntington's disease gene, but then you can also notice that the person in the lower left and the upper right. They're just like their parents. So they also have Huntington's disease and then the person all the way on the right side, on the bottom. That person doesn't have Huntington's disease. They just inherited the little a's. And so the answer to the question is 75% is the risk. That would be for each pregnancy. So it's not like if you had four kids, three of them would have it. And one wouldn't. Each pregnancy has its own 75% risk. And again, I'm going to let Dr. Wheelock sort of address the part about the person who inherits two copies of the Huntington's disease gene. I'm going to stop sharing my screen if I could figure out how to do that.
Dr. Wheelock: Thanks, Mara. Yeah, so the answer is instead of being 50 50 at 75% risk of inheriting and 25% of not, and it's a really rare situation Because Huntington's is a, is a rare disease to this group. It doesn't seem that way probably, but it's still an uncommon condition. We know about this from the cohort in Venezuela that was studied by Dr. Nancy Wexler and her team for many years. And what they noticed was that there didn't seem to be much different if you had two copies of the HD expansion, people seem to be identical or, they couldn't distinguish them from those who just had one copy, which is, very very interesting. When it comes to genetic conditions, it's a little bit surprising, but that seems to be the best answer.
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