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Hi. It's Mr. Andersen and in this podcast I'm going to talk about X-Inactivation.
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Sometimes we call this lyonization and that's kind of giving credit to the person who discovered
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most of this which is Mary Lyon. But I want to start the whole thing by talking about
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calico and tortoise shell cats. Calico cats like this one and tortoise shell cats like
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this are almost always female. Which puzzled scientists for a long time until we finally
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figured out how that works. And it puzzled Mary Lyon as well. Here she is. She worked
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at Cambridge. But basically what she found is that when she was working with lab rats,
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some of them would be a white. Some would be a grey. And some would be kind of a tortoise
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shell between to two. But what she found is that most of those tortoise shell mice were
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females. And so most of them had two X chromosomes. And she was also working on chromosomes and
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why some disorders are more prevalent in females then they are in males. And so we know that's
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sex-linkage. But basically what she found is that when you look into the nucleus of
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a cell, so this is in the nucleus, in every cell of every female, one of the X chromosomes
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will be active. And so it works perfectly. But the other one is going to be inactive.
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It's going to fall apart. And so if you're a female, in all of your cells, only one of
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the X chromosomes is active and the other one is inactive. It's okay though. Because
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you're fine. On guy's side, same thing. We only have one X chromosome and so sex chromosomes
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like this are kind of designed to just work on their own. And when it breaks apart like
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that we call that a bar body. Or that X chromosome is now inactivated. And so let me kind of
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talk you through how this works. Well basically when you were born, well before you're born,
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when you're a zygote, that zygote, if you're a female will have two X chromosomes. And
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those X chromosomes will be copied when the cell goes through mitosis. And so we go from
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having one cell to two. And then to four. And then to eight. And I could keep doing
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this, but basically when you get a big ball of cells like this, these are called stem
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cells. They're cells that can become any other cell. But right around this time when you
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start to get this big blastula there's basically a flip of the coin that goes on in each of
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the cells. And so one of the X chromosomes will simply wad up and become inactivated.
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So this one might wad up. And it's fifty-fifty chance which are the ones that are going to
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wad up. So it might be that one. It might be that one. So it's totally random which
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one's going to wad up in each of these. Now the one that's left, it's going to be able
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to express all of the genes that are found on that. And what's interesting is that all
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of the cells that come from this cell, likewise, are going to have one X chromosome that's
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inactivated. And then one X chromosome that's activated. And so basically this stem cell,
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once that flip of the coin is occurred, it's for the rest of the life of the cell and all
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the cells that come from that. And so that tells us why a calico cat is female. And let
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me talk you through that. So if you're a male cat you could basically be an orange or a
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black cat. Or you could be a white cat if you're lacking the pigment on the hair. And
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so let's look at this. So it's found on the X chromosome. If you have the black gene on
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your X chromosome, since you only have on X chromosome, then you're going to be a black
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cat. If you have the orange gene on your X chromosome then you're going to be an orange
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cat. And it's pretty straight forward. Because in every cell there's going to be an X chromosome
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with that gene making that pigment color. Now let's look at the female side. So if you're
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a female cat and you have two X chromosomes, if both of them are black gene, then you're
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going to have a black cat. Now what you should know is that in each of the cells of this
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cat that produces this black pigment on it's skin, it's going to be a different X chromosome
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that's working in each of those. So that flip of the coin has occurred. Likewise if we've
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got you know an orange gene on each of those X chromosomes, same thing. It's going to be
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orange. But what's weird is if you're heterozygous for it. So if you're this, if your a female
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who has one X chromosome with a black gene and one with a orange gene, well, how could
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this occur? Well simple. Let's say we match this, a black cat with an orange cat, and
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then all of the offspring are going to be like this. And so what is it going to look
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like? Well, this is not a great animation or a great picture, but basically what you
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will have is splotches of black and splotches of orange. And so let's look at this black
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right here. Basically what happened is at the stem cell stage, the orange gene basically,
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this orange gene became a bar body. So it became inactivated and all the cells that
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came from that produced black pigment. I think that's really cool. Likewise in one's where
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the black one wadded up, all of the cells that come from that are going to produce orange
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pigment. And so that's X inactivation. It's rare that we see this occurring and that's
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just because sex cells are designed to work on their own. The X chromosome. Now two quick
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questions you should be thinking right away. Is number one, what about the white? Why do
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we get this white coloration. Well if you remember when I talked about genetics there
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was a process called epistasis. And so basically there's going to be a set of genes that determine
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the color of the pigment that's added to the hair. But there's going to be another gene
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or set of genes that are actually going to tell us, is that color added to the hair or
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not. And that's called epistasis. And so basically in these cells we're not actually adding the
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pigment. But up here we've got X inactivation. Another question you should be thinking to
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yourself is at the beginning I said almost all calico cats that you'll ever see are going
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to be female. Well how could we ever have a male calico cat? It's pretty simple, but
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maybe non-intuitive. But basically what you could get is a XXY male. And so how does that
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occur? Well during meiosis you could get non disjunction of the two X chromosomes. And
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so basically you could get one that is of the orange. One that is of the black. And
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so you could have a, we call this Klinefelter's syndrome in humans. But you could have a calico
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male. But again, it's going to be incredibly rare. So that's X inactivation. It's rare
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that you could see this in humans. However, I was reading and there's a disorder in humans
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where they lack sweat glands. You could imagine that's really, really dangerous because you
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can't regulate your temperature. And what I found was that if you have or are heterozygous
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for this in some females, they'll actually have patches of their skin where they have
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sweat glands and patches where they don't. And that's just due to X inactivation. And
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I hope that's helpful.