Welcome back, this is the sixth module I guess in this week. And today we're just going to talk about the X Chromosome. And to kind of motivate my discussion of the X Chromosome, I'm going to ask you what type of cat that is, I'm sure, got a lot of cat people out there. And I would imagine, if you're a cat person, you recognize what type of cat this is. This is a calico cat. And if you're a real cat person, you might even know the sex of this cat. Calico cats are almost always female cats. So why is it that calico cats with this particular kind of pie balding of their fur are always female cats? It's something that we're going to explore today. And we'll come back to the calico cat in a little bit. But in order to understand the calico cat, we need to understand a little bit. About the sex chromosomes. So in humans and much like in cats, there's an x chromosome and a y chromosome, and then the other right 22 chromosome pairs are auto zones. And in humans, if you have an X and a Y chromosome you end up being a male, genetically a male. And if yo have two Xs, and here's two Xs here, you're female. And this is actually, this, this, the size of, these are actual X and Y chromosomes, and, and, reflect the relative size. The X chromosome has about 2000 genes and a 155 million or mega bases of DNA. The Y chromosome only has about 80 genes, many, many fewer genes, and is about one-third the size in terms of the number of DNA bases on that gene, about 59 megabases of DNA. Well, females have much more DNA than males then because look at their X chromosome versus the males' Y chromosome. Does this mean that women produce twice as much of the gene product for those 2000 genes on the X chromosome than the man does, right? If they have two copies and men only have one copy of these 2000 genes, are women producing twice as much? Of the product associated with those 2000 genes the protein product that men do having only one copy of that gene. Well, not really. And the reason not really that we know not really, is because of the work of this woman Mary Lyon, who actually many years ago developed a hypothesis. And the basis of her hypothesis was that if you began to look at the proteins it wasn't as if women had more of the protein associated with genes on the X chromosome than men did. So what Mary Lyon hypothesized and at this point I, I, we probably should call it Mary Lyon's model and not hypothesis because basically her hypothesis has been borne out. Has been supported by the literature. That in women only one X chromosome is actually active. That one X chromosome becomes inactivated. And that X chromosome, right, a woman has two exes. One X she received from her mother the other X from her father. So she has a maternal and paternal X chromosome. That the inactivated X is either maternal or paternal chromosome, and which one it is, is a random event. The inactivation of one of the X's occurs early in embryonic development. And in fact, probably round about two weeks. And the Inactivation is permanent in all daughter cells. So if the paternal X is X chromosome is inactivated in a cell. Every daughter cell from that cell will also have that paternal X inactivated. Over successive cell cycles, over mitosis. So let's see what Mary Lyon was talking about. Here are as a number of two pairs a pair of x chromosomes, let's say the blue one is the one that this woman inherited from her father, and the red from her mother. And at again in, in early and embryonic development there might be. I don't know how many cells. Hundreds or thousands of cells at this, this particular point in time in embryonic development. Up to that point, both Xs are active in the female genome. But at that time, randomly in each cell that exists in the developing embryo at that time. One of the Xs is going to turn off, but it's random. In this cell it turns out that this, the mother's X turned off. But in the next cell it's the father's X that turned off. So that at this point, different cells will have different X chromosomes turned off. But as Mary Lion indicated, once an X is turned off in that cell, when that cell divides and that cell division is called mitosis, and the, and the chromosomes are duplicated and producing daughter cells, this X will be turned off in all of those daughter cells. So, in subsequent cells, it will always be this sex for this chromosome. And for this line, this sex will always be turned off. This one in this line, and so on and so forth. So X inactivation occurs early in embryonic development. Is random across cells at that stage. But then once it happens, it's permanent in that cell line. The calico cat is a female who's heterozygous for a gene that codes for its coat color. It's a gene that either gives it a brown or an orange color depending upon what allele the individual has inherited. But calico cats, calico female calico cats have both alleles, they're heterozygote; on one x chromosome they have the brown allele, on the other x chromosome they have the orange allele. You get this pie balding because when the x chromosome becomes inactivated in the calico cat, in some regions it's the one, the inactivated one was the orange allele so then you get the brown fur, in the others it's the brown allele that got inactivated so you get a streak of orange alleles. That's how you get the piebalding in the calico cat. In essence, a calico cat is a mosaic. Females are always mosaic for the X chromosome. Now, you might be wondering, well, why would I single out the X chromosome in this way? Why take this time? One of the things that's going to be important here, and what the X chromosome is beginning to illustrate for us, is that there must be some form of regulation of our genetic material that turns off one of the X's. And we'll see that those mechanisms of genetic regulation. That turn off an X chromosome, will have different manifestations in different forms of genetic regulation that we're going to talk through as we finish up the various modules in this in this segment of the course. Next time we'll talk about something that also deals with genetic regulation. Prader-Willi and Angelman Syndrome. [SOUND] [BLANK_AUDIO]