In this lecture, I’d like to introduce you to chromosomal disorders. It's the first of three lectures.
We’ll be discussing nondisjunction and autosomal polyploidies. To begin with, let’s take a quick review
of chromosome structure and how we talk about each of the pieces of the chromosome. That will give us
a little orientation to where some of these disorders are located. To start with, we speak about chromosomes
based on the location of the centromeres. Here, we have a submetacentric. We call it meta, it means middle.
So, a metacentric chromosome has the centromeres right in the middle. It’s hard to talk about those
because they don’t have a long arm or a short arm. In general, we discuss chromosomes by thinking about
the long arm versus the short arm. We call the short arm p and the long arm q. Then the locations
of various disorders along a chromosome will be discussed relative to the positioning on the q arm or the p arm.
So, a metacentric chromosome again has the centromeres right slap bang in the middle.
An acrocentric chromosome, I think of acrobat flying through the sky, the centromeres are slightly
further away from the center or further away from the ground. Then telocentric, well, we know the telomeres
are right at the end. So, telocentric chromosomes have the centromeres right in the telomeric region.
Now that we have an orientation to how we locate things on chromosomes, those will become useful
as we move through the chromosomal disorders’ lectures. Moving now on to looking at chromosomal
disorders in general or chromosomal abnormalities, they have a frequency of about 1 in 154 births,
that’s live births. Now, keep in mind that 40% to 50% of spontaneous miscarriages result in
chromosomal abnormalities. That’s because our body has a whole system of checks and balances
to make sure that the developing embryo is in a healthy state before it goes on. Now, this can become
very important when discussing reproductive health and such and genetic counselling with patients
because obviously, dealing with a miscarriage is quite difficult for a family. Discussing the fact
that our bodies have this system of checks and balances in place to make sure that we have
a healthy conceptus often can help alleviate some of that stress. Now, we can divide our chromosomal
abnormalities into two basic classes. The first of which are aneuploidies. Aneuploidies have varying number
of chromosomes, technically zero. But we’ll look at how these aneuploidies play out. Another term
we might use is polyploidies for additional chromosomes. We’ll spend some time in this lecture looking at how
aneuploidies come about or polyploidies come about. Specifically, we’ll explore Down syndrome
in quite a lot of detail. The other category or class of chromosomal abnormalities are structural abnormalities.
Again, these are where we might see inversions or deletions or breaks on a smaller scale.
There’s a partial chunk of chromosome that has been changed. You can see the frequencies
of each of those here. I don’t know that it’s particularly important for you to memorize those frequencies
but just getting an idea of actually how frequent they are. If you think overall, 1 in 154 births,
that’s fairly frequent, 0.65% of conceptions could have some chromosomal abnormality.
Let’s move on now and look at how aneuploidies result. Again, thinking back to meiosis in which
our sperm and eggs are created. We have two, we will just examine just two chromosomes.
We’ve got a homologous pair that are aligned during meiosis I. That homologous pair separates
during meiosis I, at least they should. In this case, they do separate. However, during meiosis II,
this image is showing that one of the products of meiosis I has appropriate segregation at meiosis II.
However, the other does not which results in one cell having two chromosomes, so it’s actually two
sister chromatids and the other having none. So the products of these, if they’re fertilized, will end up in
zygotes that are either correct, properly diploid or you could have a triploid in the case
where the product of meiosis II ended up with two chromosomes in the cell or a monoploid where we saw
no chromosomes in that cell and the sperm brings it in. Now, let’s imagine we’re just dealing with
chromosome 21 here. We might have a triploid or trisomy 21 or a monosomy. Now, the monosomy
tends not to survive. Again, recall we talked about there being the perfect amount of gene product.
In the Goldilocks principle, we have a large bowl. There's too much gene product, it doesn’t work out.
Too little gene product doesn’t work out. But the perfect amount of gene product is what we’re looking for.
It turns out that triploidy is one of the aneuplodies of chromosome 21. It’s one of the few
that can actually persist until birth and survive through life for an extended period of time.
Now, the other option is that meiosis I is where we see the nondisjunction, the nonseparation
or nonsegregation of chromosomes. This is where the homologous pair doesn’t segregate.
So, we see that two products could end up having two chromosomes, two sister chromatids
that are the same. When we see fertilization, we have the same thing happen. We end up with
two triploid cells or two monoploid cells. Again, the triploid in certain conditions can persist.
Now, keep in mind that these graphics are showing specifically the oocyte development.
But the same thing could happen during spermatocyte development. So, the sperm could be
aneuploid or polyploid. In which case, we could see even a completely aneuploid, an embryo
completely void of chromosome 21, let’s say we’re talking about that, or you could see that the egg
comes in, the ovum comes in with one chromosome as it should and the sperm brings two.
So, we could develop triploidy in that way. Now, it tends to be much more common
in the oocyte development. Part of the reasoning for that is suggested that because the oocytes
are stalled after meiosis I as a female baby is born. So very early in development, a female is born
with all of her eggs, right? So, spermatocytes are developed throughout men’s life.
So, nondisjunction is less likely event. That’s just one of the hypotheses.
There are other ones but that's one of the leading hypotheses in that area.