Aneuploidy

Transcript

Now we’ve talked a little bit about Down syndrome today. Down syndrome is a genetic condition that you can actually see on the karyotype. So if you look at this karyotype can you see anything different? I’ll give you a big hint. Look at that one. Set 21. How many chromosomes are there … yeah, there are three chromosomes there. So Down syndrome is a situation caused by that extra chromosome number 21. We call that Trisomy 21. So, if we were counting chromosomes in that person, we’d have a total of 47, right? Now any time you have more or less than the 46 that are normal, we call it aneuploidy. Aneuploidy, and we’ll talk for just a minute about how that happens. But I want to show you one thing here. Look how big the number 1 chromosome is up here compared to say the 21. Which one do you think has the most genes on it? The one. The one, because it’s much larger, right? Yeah, so just remember that as we go along. That will come up again.

So the question is: How do we end up with an extra chromosome? How do we get aneuploidy? And I want to kind of go through how that would work. So let’s suppose this is a human egg about to be fertilized. Now before fertilization or at the time of that fertilization, something has to happen. Remember the egg, like most cells, starts out with 46 chromosomes but its got to get rid of half of them so that when the sperm comes along and makes its donation, we’ve got to get back up to 46.

So, back to high school biology. You remember these chromosomes, so let's say that we were looking at these chromosomes. Here’s three of them, as an example — three pairs of chromosomes. Now I want to show you what they’re doing, first of all, when they’re lined up like this. Let’s just focus on one. Now I’m going to paint them so that the blue one is the chromosome that came from dad and the pink one is the one that came from mom. Now they come together at a certain time in this division and they line up perfectly and they’re lined up perfectly because they do this. Did you see what happened? Do you see how some of the blue is now on the pink and some of the pink is on the blue? We call that crossing over. So what happens is when they come together, they line up perfectly so they can swap DNA. Some of the male, the dad’s, chromosome goes on the mom’s and some of the mom’s on the dad’s. It’s just like taking a deck of cards and shuffling them. That’s why you don’t look just like grandpa or grandma, which may be a good thing. Yeah, so that’s what normally happens and that’s why they come together.

Now when they come together remember again, that sperm is going to make a donation. So we’ve got to get them apart and get rid of half of them after they’ve done their little shuffling. So normally what happens is the chromosomes come together and while they’re together then, there are these spindles, these cables that come out to pull the chromosomes apart. And so the egg will then get rid of half of those chromosomes, so now there are 23. So when there’s that successful fertilization, then that egg has gotten rid of half of those so that when the male part comes and makes that connection, now we have 23 again and that’s how it’s supposed to work. Okay?

Now when aneuploidy happens, there’s a couple of ways that we think that this could happen. And one way is a process called non-disjunction. So picture here, as this sperm comes along and fertilization is taking place, if that egg hasn’t split those chromosomes equally. So imagine those cables condensing and you’ve got a frayed cable up here. So instead of pulling them apart so that all the chromosomes split equally and half go over here and half go over here, we might not be able to pull this one because the cable’s frayed and so both chromosomes go this way.

Now, if the egg gets rid of half of these, but we have an extra one here and fertilization takes place, now what? We end up with three of this chromosome instead of two like everything else. And it’s because they didn’t pull apart and that’s called non-disjunction. Okay. That’s what often times causes aneuploidy. Something about the separation, either a premature separation, but it’s unequal so that it doesn’t work the way that it’s supposed to. Okay.