In this lecture, we’ll be exploring X-linked inheritance patterns. Now, I’m sure that we’ve all covered
X-linked inheritance patterns. So, I’d like you for a moment to think about, maybe jot down
some of the things that you recall about X-linked inheritance. Then we’ll move on into the lecture.
This should look pretty familiar. When you consider X-linked inheritance, perhaps you thought about
the fact that males have an X and a Y chromosome and that females have two X’s or maybe even red-green
color blindness or hemophilia A came to mind. Those are both X-linked disorders. We will certainly
consider them in more detail as we go through the lecture. You are right to consider that the X and Y
component of a male which brings up the concept of hemizygous, meaning having half of the genetic
material for that particular chromosome because we have only one X and the female has two X’s.
But because the female has two X’s, there are multiple options for expression. We can have
homozygous wild type, meaning the normal type or we could have homozygous for the mutant condition
which is truthfully quite rare, especially if both alleles are from the exact same place. We’ll discuss that
in a little more detail later. Also, a female could be a carrier. They are heterozygous. They could have it
hidden on one X and expressed on the other, although it turns out it’s not quite that simple.
We’ll explore some of those situations later. Then finally, you have the option of being compound heterozygote.
That is the condition where we have two mutant alleles but they are from a different background.
Now, that’s a concept that I introduced in an earlier lecture. So, I just wanted to cover it again.
Let’s look at a particular condition that exhibits some of the things that come a little bit confusing
about X-linked inheritance. Classically, we talk about dominant and recessive X-linked characteristics.
But in this lecture, perhaps you’ll recognize that it’s not really quite that simple. In fact, some people
have talked about doing away with talking about dominance and recessiveness with X-linked traits
because it’s quite complex. When you consider expressivity and penetrance even in autosomal conditions,
it sort of clouds the picture a little bit. But let’s take a look now at what happens when you consider mosaicism, right?
As you’ll recall, we have two X chromosomes in the female condition. One of them will become a Barr body.
Let’s look at these fluorescence micrographs for Duchenne muscular dystrophy. First of all,
Duchenne muscular dystrophy, we consider as an X-linked recessive condition. It’s caused by a missing
dystrophin protein. Dystrophin is a protein that surrounds the muscle fiber cells and holds them intact,
keeps them together. In the case of X homozygote, so female homozygote, she shows dystrophin
around each of the cells here. As you might predict, a male having the regular dystrophin allele shows
or a mutant dystrophin allele is going to show no dystrophin around the muscle cells as you can see here
in this picture. Now, we’re presented with a different case when we consider a female carrier.
This is just to show the range of expressions that you might see in a female carrier. Here, we have
some cells that are showing the dystrophin protein around them and other cells that are not showing
the dystrophin protein. Yes, you’re right. That is because alternately, one of the X chromosomes has formed
a Barr body. So, you have mosaicism, patches of muscle tissue that have the dystrophin protein intact
and patches of muscle tissue that have the dystrophin, the disrupted dystrophin. So the cells don't stay
as intact. We sort of are seeing a continuum of the effect in a heterozygous female dependent on
where the corresponding X chromosome has become a Barr body. Maybe it’s not in the muscle tissue at all.
Maybe it’s in some muscle tissue and not other muscle tissue. So, we can definitely see a broad range
of expression in these X-linked characters. Now, is that heterozygote showing dominance? Perhaps it is.
Again, that’s where it becomes a little cloudy. Here is a pedigree of X-linked recessive disorder.
They’re easily recognized. Perhaps you could take a moment and consider two things that are
characteristic of an X-linked recessive inheritance pattern. Here, the image is showing as hemophilia A
which is a classic X-linked disorder you’re probably familiar with already. It has to do with the missing
factor VIII clotting factor and so blood doesn’t clot properly. People historically have bled to death.
You may remember it as the royal clotting disorder because Queen Elizabeth had that and passed it on
to many of her male progeny. The first thing you might notice is that all males that receive the allele
express the allele because they only have one copy. There’s nothing to be made up for
on the other X chromosome. You’ll also notice often that it skips a generation or there’s a pattern
of skipping the generation because females will be carriers. They have an extra copy of the factor VIII
in general. So, they are not affected by the disorder of clotting. Easily to recognize when it’s a distinct
character like this but not always so easy to recognize if we have penetrance issues, so on and so forth.