Sex Chromosome Aneuploidies

00:00 The critical thing here to understand is lots of different conditions can arise even though chromosomally an individual may appear to be male or female. Many things could happen along the way. All of those things that we’ve previously considered are chromosomal structural changes. Now, we’ll step into the sex chromosome aneuploidies or polyploidies. The interesting thing is that sex chromosome aneuploidies and polyploidies can be tolerated much more easily than aneuploidies of autosomes. It seems that the dosage, just the right amount of gene product isn’t such a big issue. Well, I’m sure that you can probably answer the question why at this point. Think to yourself, what is it that’s different about the sex chromosomes than the autosomes? First of all, you know that there’s an X and an X, and an X and a Y. We’ve already certainly talked about the idea of dosage compensation.

01:18 Aneuploidies of X chromosomes are fairly common actually because of the dosage compensation piece, right? So, you’ll recall that because a male has an X and a Y and females have X and X, in order to make the dosage similar between the sexes, the extra baggage or whatever on the X chromosome has to be hypermethylated and condensed. It condenses into a Barr body. We’ve certainly talked about this a number of different times. But it’s because of this dosage compensation that the X chromosome aneuploidies or polyploidies in fact could be much more easily tolerated. Because what happens, as you can see in these images is that the number of inactive X's, so let’s say we have a polyploidy, we have three X's or even four X's because nondisjunction happened twice. We can actually see up to six or eight X's and have a viable child born. That is because of this dosage compensation and the formation of Barr bodies. You can see in the figure here that we have histone labeled, FISH labeled, FISH screens labeled with histone variants for picking up inactive X chromosomes. What you see in these images is that the top left one, you can see that there’s one labeled. So that means there’s one inactive chromosome and two inactive chromosomes, three inactive, four inactive chromosomes.

03:04 So, this individual on the bottom right has 49 chromosomes but most cells have or all the cells have at least four of those inactivated. Again, you can see the possibility here for multiple mosaic type patterns.

03:25 Clearly, when we think about X chromosome aneuploidies and polyploidies, it’s going to have more of an impact on X linked characteristics than it is any others. But I think it’s very interesting that we can tolerate so many different X's and they all get made into Barr bodies. Now, we might ask, “Well, can we have only one X chromosome?” The answer to that question is well, we can.

03:59 But it turns out that two X's, it’s a viable situation, but two X's are necessary for ovarian maintenance throughout the end of reproductive years. So anyone that just has one X chromosome as we’ll see with Turner syndrome situation here shortly, they will not be fertile generally. You must have at least one of the X's inactivated or all of the extra X's inactivated in order to have normal development.

04:36 If two X's are expressed, then we see that development is not normal.