Video Transcript
In this video, we’ll learn more
about chromosomal abnormalities. We’ll cover some common
abnormalities, such as Klinefelter syndrome, Turner syndrome, and Down syndrome. We’ll learn more about a karyotype
and how do we interpret this to identify these kinds of chromosomal
abnormalities.
We can find our DNA in the nucleus
of most of our cells. We have a lot of it. If we were to take out all the DNA
from the nucleus and line it up, we would get about two meters worth of DNA in a
single human cell. This DNA isn’t one continuous
molecule. Instead, we have 46 molecules of
DNA inside our cells that we call chromosomes. Let’s take a closer look and see
what these look like. Our chromosomes are numbered one to
22, with chromosome one being the largest and 22 being the smallest. We call chromosomes one to 22
autosomes.
We also have chromosomes X and Y,
which we call the sex chromosomes because they determine our biological sex. Having one copy of the X chromosome
and one copy of the Y chromosome produces a biological male, while two copies of the
X chromosome produce a biological female. We have two copies of each
chromosome that we call a homologous pair. We get one copy from our biological
father and the other copy from a biological mother. So, we really have 23 pairs of
chromosomes. To give a total of 46
chromosomes. We can actually see how many
chromosomes our cells have by performing a karyotype.
A karyotype, like the one shown on
the right, is an image of an organism’s chromosomes that can be used to look for
chromosomal abnormalities. The problem is most cells don’t
have their chromosomes in its compacted and X-shaped structure that we see here. A typical cell will have its DNA
all mixed up, like we see here. This big mess has 46 individual
chromosomes, but it’s not possible to see them separately. In real life, they’re not colored
blue and pink as we’re showing here. So, to perform a karyotype, we have
to pause the cell during a critical point of the cell’s division where they take on
this condensed and X-shaped structure. Let’s look at this in more
detail.
You’ll recall that the cell cycle
is a series of phases that dividing cells go through in order to divide. It’s separated into interphase and
mitosis. During interphase, the cell copies
its DNA so it can be separated into a new cell during mitosis. In interphase, the cell’s
chromosomes are all mixed up as you see here. To make things a little easier to
see, let’s just look at one homologous pair. So now, we see the two copies of a
single chromosome, which are long molecules of loosely compacted DNA. During interphase, these
chromosomes replicate to make a copy of themselves. Then, as a cell enters mitosis,
these replicated chromosomes compact or condense to eventually form this familiar
X-shaped structure, which you can see over here.
These duplicated and condensed
chromosomes are what we want in a karyotype because it makes it much easier to
identify each chromosome because they’re condensed and not long strings of DNA
anymore and they’re all separated from each other. If we were to let the cell continue
through mitosis, then the duplicated chromosomes would separate as the cell prepares
to divide. And this is what normally happens
during mitosis. But we don’t want this to happen
because these duplicated and condensed chromosomes are exactly what we’re looking
for for our karyotype. So to prevent mitosis from
continuing on, we use a chemical called the mitotic inhibitor to prevent mitosis
from continuing. Mitosis is therefore paused just at
this perfect moment where the duplicated and condensed chromosomes are.
Remember, we’re just showing one
homologous pair here. But in reality, there’s 23 pairs or
46 chromosomes in total. It’s not quite 46, but it gives you
an idea of what this might look like. So now that mitosis is paused at
just the right time, we take a picture and use a computer to organize the duplicated
and condensed chromosomes to give the karyotype that we see here. This makes it very easy to see if
there’s any differences in the chromosome number and structure.
So now that we know how to do a
karyotype, we found that in certain individuals there are different chromosomal
abnormalities. In some cases, structural changes
to chromosomes can occur where parts of a single chromosome can be deleted or
duplicated. And in other cases, individuals may
have an extra copy of a chromosome, so now there’s three copies. And in other cases, one of the two
copies of a particular chromosome might be missing altogether. This can happen because of errors
during the formation of the sex cells or gametes, such as the egg or sperm
cells.
Each gamete has half the number of
chromosomes needed to form the embryo. So instead of having 23 pairs, the
sperm cell just has one chromosome for each of the 23 different chromosomes, as
shown here in blue. And the same goes for the egg cell;
it just has one copy of each of these 23 chromosomes, shown here in pink. This way when a sperm fertilizes
the egg, the 23 chromosomes from the sperm come together with the 23 chromosomes in
the egg to make the 46 chromosomes in the zygote. This can then go on to develop into
an embryo and a baby with the proper number of chromosomes.
This sperm and egg came from the
biological father and biological mother, both of whom had 46 chromosomes. These 46 chromosomes are split in
half to make gametes that contain 23 chromosomes during a special type of cell
division called meiosis. Although only two gametes are shown
here from each parent, meiosis actually produces four gametes from a single cell,
but two are shown here for simplicity. Sometimes errors in meiosis don’t
reduce the chromosome number properly and an egg or a sperm cell can have an extra
chromosome or one might be missing a chromosome.
So, when the egg and sperm come
together during fertilization, the resulting zygote will have a chromosome number
that isn’t 46 and is therefore abnormal. These abnormal chromosome numbers
can cause a variety of syndromes, and we’ll talk about that in a moment. But first, why is this so important
to have 46 chromosomes and not any more or less? Each chromosome has a lot of
information. Chromosome one is about 249 million
base pairs long and has about 2000 protein-coding genes. If we look at all of our
chromosomes, we have about 20,000 protein-coding genes in all. And we have two copies of each
chromosome.
So here’s chromosome one with its
two copies. And let’s say that there’s three
genes being expressed that we’ll call A, B, and C. And on the bottom, we can see that
these genes are being expressed at different levels. Gene B is being expressed twice as
much as gene A, for instance. Inside the cell, these expression
levels are carefully coordinated and balanced to give us these amounts. So, what happens if we add another
chromosome? Since we now have three copies of
chromosome one and therefore another copy of genes A, B, and C, the expression
levels of each gene increase, and this might not be good for the cell.
Imagine baking a cake and using too
much flour or sugar or some other ingredient. The results might not be very
good. Likewise, our cells are optimized
to use two copies of each gene in most cases. And by changing these amounts, the
cell can suffer. This concept is called gene dosage
and is why having an extra copy of a chromosome can cause problems. While having an extra chromosome
can be tolerated in some cases, having only one copy of a chromosome is often
lethal. In this case, the expression of
these genes is too low and many cells can’t function normally. So having a single copy of a
chromosome can be lethal, often very early as an embryo.
Now that we understand karyotypes,
how we get abnormal chromosome numbers, and why this matters, let’s look at some
real-life examples and see what the impact is. The first example we’ll look at is
with Down syndrome. Down syndrome was first identified
in a group of patients by the physician Dr. John Langdon Down.
In Down syndrome, we have an extra
copy of chromosome 21. So, these individuals have a total
of 47 chromosomes rather than 46. Having an extra copy of chromosome
21 often causes different physical and mental traits associated with the
syndrome. These include delays in language
development, heart defects, a flattened facial profile. Individuals with Down syndrome are
generally shorter in height, have short, broad hands, and have issues with
learning.
With appropriate support, most
adults with Down syndrome are able to have a high quality of life and live
independently. Down syndrome is a good example of
what happens when there’s an extra autosome. But what about the sex
chromosomes? Klinefelter syndrome was first
described by Dr. Harry Klinefelter in a group of men. Klinefelter syndrome is
characterized by an additional X chromosome. So, they have a total of three sex
chromosomes and 47 chromosomes in all.
Some of the characteristics of
Klinefelter syndrome are that they are tall in height, they have infertility
problems, reduced development of facial hair, and more pronounced breast
development. Some of these traits are caused by
decreases in the hormone testosterone. Even though there’s an extra X
chromosome in these individuals, they still have the Y chromosome as well, which
allows them to develop male reproductive organs normally. Because the traits of this syndrome
can be mild, many males with Klinefelter syndrome are never diagnosed and have a
high quality of life.
Turner syndrome was first described
by doctor Henry Turner who was studying a group of females. Normally, females contain two
copies of the X chromosome as we can see here. But in Turner syndrome, females
only have a single copy of the X chromosome, so they have 45 chromosomes in total
instead of 46. Turner syndrome is actually the
only example where having a single copy of a chromosome is tolerated. As mentioned earlier, loss of a
chromosome is often lethal for the embryo.
Some characteristics of Turner
syndrome include a webbed neck, where they have extra folds of skin in the neck
area, defects in the heart and kidneys, infertility problems, and they’re generally
short in height. Because the X chromosome is missing
which contains the genes for female hormones, like estrogen, there is a reduction in
reproduction. This can lead to underdevelopment
of the ovaries and infertility. Hormone therapy can be used to
support these individuals who can then go on to have a high quality of life.
Now, let’s take a look at a
practice question to apply what we’ve learned in this video.
The passage provided outlines how
chromosomal abnormalities can be caused. Chromosomal abnormalities can be
caused by changes in the blank of chromosomes or a complete loss or blank of entire
chromosomes. Which word would be most
appropriate to replace the first blank? (A) Appearance, (B) bonding, (C)
replication, or (D) structure.
This question is asking us about
chromosomes and chromosomal abnormalities. So let’s take a moment to review
what a chromosome is. Inside most of our cells, we have a
nucleus which contains our DNA. This DNA is organized into 46
chromosomes that we could see here. Chromosomes are numbered from one
to 22, with chromosome one being the largest and chromosome 22 being the smallest,
while chromosomes X and Y are sometimes called our sex chromosomes because they
determine our biological sex.
We have two copies of each
chromosome. One comes from our biological
father and the other comes from our biological mother. So, in total, we have 23 pairs of
chromosomes for a total of 46 chromosomes. If we take a closer look at one of
these chromosomes, we can see that there are many genes within it. These genes are needed for the cell
and for us to properly function. Chromosomal abnormalities exist in
some individuals where parts of a chromosome are missing or duplicated. These kinds of structural changes
in a chromosome can impact the genetic information on it and cause problems for the
cell. Therefore, the word that is most
appropriate to replace in the first blank in this passage will be “structure.”
Now, let’s look at the second part
of this question.
Which word would be most
appropriate to replace the second blank? (A) Fusion, (B) specialization, (C)
segmentation, or (D) gain.
Besides structural changes in a
chromosome, entire chromosomes can be missing or duplicated. Some syndromes, such as Down
syndrome, are caused by an additional copy or a gain of chromosome 21. Because there’s now three copies of
this chromosome, there’s now additional copies of the genes that it contains. This additional genetic information
can cause problems for the cell that are manifested as Down syndrome. Therefore, the word that’s most
appropriate to replace the second blank is “gain.”
Therefore the passage now correctly
reads “Chromosomal abnormalities can be caused by changes in the structure of
chromosomes or complete loss or gain of entire chromosomes.”
Now let’s go over the key points
that we covered in this video. Humans have a total of 46
chromosomes or 23 pairs of chromosomes. A karyotype is an image of an
organism’s chromosomes and is what we use to identify any chromosomal
abnormalities. Errors in forming gametes, like the
egg or sperm cell, can cause a gain or loss of chromosomes. Down syndrome is caused by three
copies of chromosome 21 instead of the normal two copies. Klinefelter syndrome affects males
and is caused by two copies of the X chromosome and a single copy of the Y
chromosome. Turner syndrome affects females and
is caused by a missing X chromosome. So, these females only have a
single copy of the X chromosome instead of having the normal two.
