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