[Instructor] Hello and welcome to Module Four.
This first lecture focus on aneuploidy.
We'll talk about what it is, how it occurs,
and some of the clinical manifestations.
So let's jump right in.
First, a quick review from our previous module.
Mitosis is the process of cell division,
which occurs in somatic cells
to produce two diploid daughter cells.
Recall that somatic cells are basically all the cells
in your body with the exception of egg and sperm cell.
Those egg and sperm cell are called gametes,
and the cells that lead to gametes,
so the cells which will develop into gametes,
are called germline cells.
In Meiosis, this is the process of cell division
which occurs in those pre-gamete cells,
also called germline cells,
to produce four haploid gametes.
Gametes, or egg and sperm, must have 23 chromosomes each,
one copy of each, so that when they fuse
the resulting fertilized egg
will have the correct number of 46 total chromosomes.
In Meiosis I, remember that there are two phases of Meiosis
that follow one another.
The first major stage is Meiosis I,
and this is when homologous chromosomes separate.
In Meiosis II, which follows Meiosis I,
and also in which occurs in mitosis
is sister chromatids will separate.
Let's take a peek at a human karyotype.
Recall that karyotypes are basically microscopic examination
of each of the chromosomes.
And they're oftentimes they're done to identify
if there's an aneuploidy in an individual
or an improper number of chromosomes.
So they're aligned here and spread out,
and identified by their chromosome number or identification.
Each chromosome has two copies, one from mom, one from dad.
So in total we have 46 chromosomes.
Remember that the two copies of each chromosome
are homologous chromosomes.
Each chromosome contains a specific set of genes
and the chromosomes are numbered
one through 22 for autosomes.
The remaining are sex chromosomes,
two X chromosomes would be female,
one X and one Y would be male.
A quick review of Meiosis as well, and normal Meiosis.
There again, there are two phases.
The first phase, Meiosis I,
is when the homologous chromosomes align
and are separated from one another,
creating two daughter cells each with 23 chromosomes.
But each of those has a sister chromatid,
if you remember that the sister chromatids
are the identical copies of the chromosome
which were created during DNA replication.
And those sister chromatids are separated from one another
during Meiosis II.
Sperm cells determine the sex of the embryo
and the sperm with the X chromosome
results in a female embryo,
while sperm with the Y chromosome
will result in the male embryo.
And these numbers are indicating 22,
which would be the number of autosomes
each of these cells has.
And then neither has, well, in the case of females,
there'll always be 22 autosomes plus an X chromosome
because all females have two X chromosomes.
In males, however, you have an X and you have a Y.
And during Meiosis, the X and Y chromosomes
actually will pair together as homologous chromosomes
and will be separated from one another.
So 50% of the sperm will have an X chromosome
and 50% of the sperm will have a Y chromosome.
If the sperm that fertilizes the egg has an X chromosome,
this will become a female.
If the sperm has a Y chromosome, this will become a male.
So why do we need exactly 46 chromosomes?
Well, each chromosome has many genes,
anywhere from 2,000 genes on chromosome one,
which as you can recall is the largest chromosome,
to around 50 genes on the Y chromosome,
and Y chromosome is the smallest chromosome
that humans have.
Cells have adapted a finely tuned balance
of gene regulation systems based on having
exactly two copies of the genes on autosomes.
So changes in the number of autosomes
affect gene expression.
So remember that's a big deal.
If you have too many copies or too few copies of something
and transcription is occurring at its regular rate,
well if you have 50% more of that gene present,
which would mean say you have three copies
instead of two copies,
then you're going to have 50% more of that protein around,
which completely throws off
many of the functions in the cell.
So this is a real problem.
If say on the other hand you only have one copy
instead of two copies in a somatic cell,
well then that means only half of the
normal amount of protein will be formed
for the genes on that chromosome code for.
So it's really, really important
that you have the right number because
we have adapted a system in which you need
exactly two copies on autosomes.
It's a little bit different on the sex chromosomes
and we'll talk about that in a little bit.
Having an extra autosome will result in too much expression
of all of the genes on that chromosome
because there are three copies being transcribed.
Again, and having only one copy of an autosome,
so for example, only one copy of chromosome 12
would result in too little expression
of all of the genes on that chromosome
because only one copy is being transcribed.
Either way it's bad and it's usually incompatible with life.
There are a few exceptions to this,
but the general rule is if you have too many
or too few of any chromosome,
that those cells cannot survive.
So what can go wrong here?
Aneuploidy is the incorrect number of chromosomes in a cell,
either too many or too few.
And they're further sort of categorized
or defined clinically as trisomy.
And that's one extra copy of a chromosome.
So why is it called trisomy?
Tri- being three. So three copies of a chromosome.
You normally have two copies of each chromosome,
so that would be an extra, one extra copy.
So that would be trisomy.
Tetrasomy would be two extra copies, Tetra- being four.
So it would be a total of four copies of an autosome.
Monosomy would be one fewer copy of a chromosome.
So mono- being one.
So you would only have one copy of an autosome, for example.
Nullisomy would be zero copies of a chromosome.
So you completely do not have
one of the particular chromosomes.
Aneuploidy occurs when chromosomes do not divide
evenly in Meiosis I or II,
which would create an egg or sperm
with the incorrect number of chromosomes.
So the resulting fertilized egg
created with one of these cells
develops into a zygote with too few or too many chromosomes.
And as you recall, this is really problematic
for the levels of gene expression
for all of the genes on the chromosome
that either has too many or too few copies.
Aneuploidy is the leading cause of spontaneous abortions
because the embryo simply cannot survive
with the wrong number of chromosomes,
with a few exceptions and we will talk about those.
But generally the vast majority of the chromosomes,
you cannot have the incorrect number
and have an embryo actually survive and develop.
That's how important it is to have gene expression
be perfectly regulated and be exactly correct.
Otherwise, the entire system falls apart.
In surviving aneuploidy, the child will have a syndrome
with usually widespread and various health conditions
depending on the chromosome affected.
And there really are only a few chromosomes
that you can have aneuploidy and have any expected survival.
So let's take a peek at what could go wrong here.
So it could happen, remember,
it could happen again in either Meiosis I or Meiosis II.
So if it's happening in Meiosis I,
what's actually happening is an event
called nondisjunction.
Nondisjunction means that chromosomes
are not properly separating from one another
during a process of cell division.
In the case of Meiosis I,
nondisjunction would happen between homologous chromosomes
because it's in Meiosis I when homologous chromosomes
are supposed to separate from each other,
go to opposite sides to form two new cells.
If that does not happen, and this is showing here
that these two homologous chromosomes
are both going to one cell,
which results in two cells coming out of Meiosis I.
One which has two copies of this particular chromosome
and one which has zero copies of that chromosome.
This is followed up by Meiosis II in these cells
where the end result is
if the sister chromatids then separate
and this is denoted here,
'n' being denoted as the correct number of chromosomes
that should be present in the cell.
And this is being designated as how many additional
or how many fewer chromosomes.
So in a gamete that has the proper number of chromosomes,
it would just be designated as 'n.'
In a gamete with one additional chromosome it would be 'n+1'
With one fewer, it would be 'n-1.'
If you were looking at the same,
if you were looking at the same way of denoting it
in the same way of denoting the number of chromosomes
in a somatic cell,
which has two copies of each chromosome,
you would denote that as '2n,'
or two times the number of chromosomes.
All right, so the other possibility
of when an aneuploidy event can occur
would be in Meiosis II.
So let's assume Meiosis I happens normally
and you produce two cells,
each has one copy of each of the chromosomes.
Well now you have to separate
the sister chromatids in Meiosis II.
And during that process, nondisjunction can also occur here.
Nondisjunction being a lack of separation
in the case of Meiosis II of sister chromatids.
So both sister chromatids for one chromosome
will go to one cell, and the other cell will receive
no copies of that particular chromosome.
Since this is happening in Meiosis II.
this cell that was the other product
of the original normal Meiosis I event
has the correct number of chromosomes
and so it will undergo normal Meiosis.
And if it undergoes normal Meiosis II,
it produces two normal gametes with the designation of 'n.'
In the case where there was
nondisjunction in Meiosis II in this cell,
it will result in one gamete that has 'n + 1' chromosomes,
or one additional chromosome,
and one gamete with 'n - 1' or one fewer chromosome.
So let's review this all together.
Meiosis I aneuploidy.
In normal Meiosis I, this is when homologous chromosomes
separate to two daughter cells,
which then is followed by Meiosis II.
In nondisjunction, this results when homologous chromosomes
both go to the same daughter cell and are not separated.
This results in two gametes with one extra chromosome
and two gametes with one fewer chromosome.
Most aneuploidy occurs from nondisjunction in Meiosis I
because of crossing over, remember crossing over?
and that's when homologous chromosomes all start to like
swapping bits and pieces with each other.
While during this process, they are actually
physically being connected to one another.
If the process doesn't occur properly
and if crossing over does not complete normally,
then it becomes very difficult for these chromosomes
to physically separate from one another.
And you can have nondisjunction.
Meiosis II aneuploidy,
if the aneuploidy event occurs in Meiosis II,
if you recall Meiosis II is when sister chromatids
separate to the two daughter cells from Meiosis I
to create four daughter cells,
each with one sister chromatid for each chromosome.
Nondisjunction results when sister chromatids
both go to the same daughter cell and are not separated.
This results in one gamete with one extra chromosome,
one gamete with one fewer chromosome,
and two normal gametes.
Let's talk a little bit about
some of the nomenclature and statistics
associated with aneuploidy.
So aneuploidy is denoted using
a common karyotype nomenclature,
which would be the total number of chromosomes, comma,
the sex chromosomes present, comma,
and then here would go the any derivation from that.
So any aneuploidy would be denoted here
as either plus, if it's a trisomy for example.
And then the number of the autosome
which is the improper number,
or minus in the case of monosomy,
or the loss of one with the chromosomes
and then that particular number.
So let's take a look at an example.
A male with Down Syndrome, which is trisomy of chromosome 21
is denoted as 47,
because instead of having the normal 46 chromosomes,
he has 47 given that he has an extra chromosome 21.
So it would be denoted first as 47, comma, XY,
'cause he's male and has both X and Y chromosome,
and then +21.
And that indicates, plus is that there's an addition to 21.
Or sometimes it can just be denoted for short as +21.
This does not tell you the sex of the individual,
but it could just tell you that
this person has Down Syndrome.
A female with monosomy of X chromosomes,
is also called Turner Syndrome, would be denoted as 45
because instead of having 46 chromosomes, she has 45,
she's missing an X chromosome,
comma X, and just X.
And why is that? Because she only has one X chromosome.
So that's denoting the aneuploidy right there.
We don't need to put anything else with that
because you're denoting, it would be expected
in a normal individual to have either XX or XY.
So just denoting it as X indicates
this person has monosomy of X chromosome.
A normal male would be denoted as 46
'cause you have, that's the normal chromosome number,
comma XY.
A female with monosomy of chromosome 13 would be 45.
Again, she's lacking one of her chromosomes.
Comma XX, 'cause she's female.
Comma -13, minus meaning that you're lacking a chromosome.
Which chromosome? Chromosome 13.
All right, a few statistics here.
30% of all pregnancies are estimated
to result in spontaneous abortion.
That's of all pregnancies.
Most are occurring before the woman knows she is pregnant.
What's actually happening here?
Well it's estimated that 50 to 70%
of all spontaneous abortions are due to aneuploidy.
If you remember, I had mentioned
that it is not consistent with life.
And so in the majority of aneuploidy cases,
the embryo simply will not survive,
and a spontaneous abortion will result.
Of live births, about approximately one third of 1%
are a born with an aneuploidy.
The most common of those including
trisomies of chromosomes 13, 18 and 21,
having an extra X chromosome in females,
having an extra X chromosome in males,
having an extra Y chromosome in males,
or lacking an X chromosome in females.
You can take a look at this table listed below
for some more statistics on the time and gestation
when these spontaneous abortions may occur.
Let's take a quick peek at a karyotype
of someone with Down Syndrome
compared with a normal male karyotype.
So the Down Syndrome female,
this is a female, and we know this why?
Well, we can look here and see in the X chromosome category,
she has two copies.
And this would be where Y would be located.
There's no chromosome, this is a female.
How do we know this individual has Trisomy 21
or Down Syndrome?
We can look here at chromosome 21
where we see one, two, three copies.
Three copies of chromosome 21,
that's trisomy 21 or Down Syndrome.
Let's talk through some of the aneuploidy syndromes
that are most common.
Down syndrome occurring in one in 830 live births in total.
Now, the incidence of Down Syndrome increases dramatically
with maternal age and we'll talk some more about that later.
The karyotype designation would be written as 47 comma,
and then if it's a female "XX,+21,"
if it's a male "47,XY,+21."
It's associated with intellectual disability,
characteristic facial appearance, and hypotonia in infancy.
All affected individuals experience cognitive delays,
but the intellectual disability is usually mild to moderate.
Approximately 50% are born with a heart defect
and increased risk of other medical conditions
developing as well as hearing and vision problems.
Delayed development and behavioral problems
are often reported.
Speech and language develop later
and more slowly than in children without Down Syndrome,
and affected individual's speech
may be more difficult to understand.
Behavioral issues can include attention problems,
obsessive compulsive behavior, and stubbornness or tantrums.
And there's a gradual decline in cognition
as the individual ages, usually starting around age 50.
And approximately half of adults with Down Syndrome
develop Alzheimer's disease
usually developing that in their fifties or sixties,
which is earlier than individuals
who do not have Down Syndrome.
So why would this be compatible with life?
Let's go back for just one second
and we'll take a peek at chromosome 21.
What do we notice about chromosome 21
compared with all of the other chromosomes?
Well, it's pretty small.
It's pretty small, right?
So the number of genes contained on chromosome 21
is relatively small.
When there's an extra copy around,
the cells can adapt to at least remain alive.
However, there certainly are deficits
in certain cell functions and the structures that form
within those individuals.
And it's very complicated because
we're not looking at a single gene here,
we're looking at a chromosome full of genes
and we are adding an extra copy.
So it's going to be just a combination of effects
on many different genes which
code for many different proteins
and will impact various different functions
within cell and an individual.
So as a result with Down Syndrome,
as well as with really any other aneuploidy syndrome,
you have a spectrum of conditions that can result.
So it's not just one single thing.
It's going to be a variety of different
aspects of normal growth, development, and function,
which can be affected.
Edwards Syndrome, this occurs in one in 5,000 live births
and is a trisomy of chromosome 18.
And so it would be designated as you see up above here.
It's associated with abnormalities
and many parts of the body
often have slow growth before birth and low birth weight.
Heart defects and abnormalities
of other organs that develop before birth are common.
And other features of trisomy 18 include
a small abnormally shaped head, a small jaw and mouth,
and clenched fists with overlapping fingers.
Due to the presence of several
life-threatening medical problems,
many individuals die before birth
or within their first month.
Five to 10% of children with this condition
will live past their first year,
and these children often have
severe intellectual disability.
So this is a more severe condition than Down Syndrome.
And this is a trisomy, again, in chromosome 18
Patau Syndrome, which is a trisomy of chromosome 13
designated here, occurs in one in 16,000 live births
and it's associated with very severe intellectual disability
and physical abnormalities in many parts of the body.
Heart defects, brain or spinal cord abnormalities,
very small or poorly developed eyes,
extra fingers or toes, a cleft lip
with or without a cleft palate, and hypotonia are common.
Due to the presence
of several life-threatening medical problems,
many infants with Trisomy 13 die within their first days
or weeks of life.
And only five to 10% of children with this condition
will live past their first year.
Let's go back for a moment to our karyotype
and let's take a look at chromosomes 13, and 18, and 21.
And as you recall, so Trisomy 21 is Down Syndrome.
Trisomy 18 is Edwards Syndrome.
Trisomy 13 is Patau Syndrome.
And with increasing severity you have
Down Syndrome being the most compatible with life.
Trisomy of the 18 chromosome, trisomy of chromosome 18,
being more severe with Edwards Syndrome.
And you can see, perhaps you can start to hypothesize why.
This is a larger chromosome,
it's going to have more genes on it,
it's going to have potentially a bigger impact
on the overall survivability of that individual.
And then finally, chromosome 13, Patau syndrome,
which is an extremely severe condition
and most individuals do not survive past
really the first weeks of life.
So what we've been talking about so far
has to do with the autosomes,
but what about changes in our sex chromosomes?
And if we start to think about it, are we all aneuploid?
Because females have two copies of every chromosome
including X, but have no Y chromosomes.
So are females, nullisomy for the Y chromosome?
And males have only one copy of X and one copy of Y,
so are they monosomy for X chromosome
and monosomy for Y chromosome?
Well, the interesting thing here is that
cells have adapted to use only one X chromosome.
And then the genes on the Y chromosome,
remember the Y is the smallest chromosome that we have,
all the genes on the Y chromosome
are really used for sex determination
and are not necessary for survival.
So by default we are all female
unless a Y chromosome is present to make us male.
Females inactivate one of their X chromosomes in each cell
to balance it out, which means that no genes
are transcribed from that inactive X chromosome.
This is accomplished by extensive DNA methylation
that sound familiar, I hope,
of the copy of the X chromosome which will be inactive.
This is called X inactivation.
So basically in females, a cell will select
one of the two X chromosomes
and it will inactivate one of those two by methylating it,
by basically attaching methyl groups
throughout the X chromosome to completely shut it down.
So no genes are transcribed
off of that inactive X chromosome.
And in that way, males and females both have
one copy of the X chromosome,
which is active and being transcribed.
Having an incorrect number of sex chromosomes
has less severe impact on health of the individual
than aneuploidy of autosomes.
And let's look at a few examples of those
because those are actually more common
than the autosomal aneuploidies.
So trisomy X, or triple X Syndrome,
which would occur in females.
So in females we would have,
with the syndrome would have 47 chromosomes
and then they would have three X chromosomes.
This occurs in one and 1,000 newborn girls.
And although females with this condition
may be taller than average,
they typically have no unusual physical features.
Most have normal sexual development
and are able to conceive children.
This is associated with an increased risk
of learning disabilities and delayed development
of speech and language skills,
but it's pretty mild.
Seizures or kidney abnormalities occur
in about 10% of affected females.
And due to mild symptoms, most trisomy X females
are actually never diagnosed.
Oh, and this is a picture of a
beautiful baby girl with trisomy X.
She is perfectly normal and would be
really not viewed any differently
from anyone else on the street that you walk past.
You would not assume that she has a trisomy.
Turner Syndrome, this is basically a loss
of one of the X chromosomes.
This is basically a monosomy of X chromosome in females.
So it would be designated 45
because there are 45 chromosomes.
The individual would have 44 normal autosomes
and then simply one X chromosome.
So 45 chromosomes in total.
And then would be designated as comma X
because there's only one X chromosome.
Occurs in one in 2,500 newborn girls.
And the most common feature is really just a short stature.
You can see here these are two sisters.
The sister, the woman on the left here,
she has Turner Syndrome and on the right she does not.
The most common feature is short stature.
An early loss of ovarian function is also very common
and many affected girls do not undergo puberty
unless they receive hormone therapy.
And most are infertile.
About 30% of females with Turner Syndrome
have a webbed neck, low hairline,
and low hairline at the back of the neck,
puffiness or swelling of the hands and feet,
skeletal abnormalities or kidney problems.
About 30 to 50% are born with a heart defect
and most girls and women with Turner Syndrome
have normal intelligence.
So it's not as though there's any intellectual disability
with Turner Syndrome.
Klinefelter syndrome, this occurs in males where,
this occurs in males who have two X chromosomes
as well as a Y chromosome.
If you recall, I mentioned that having a Y chromosome
basically makes an individual male.
In the case of males with Klinefelter syndrome,
they also have two X chromosomes.
So this would be designated 47
for a total number of chromosomes, XXY.
This occurs in one in 500 to 1000 newborn boys.
It results in small testes that do not produce
as much testosterone as usual,
which leads to delayed or incomplete puberty,
breast enlargement, reduced facial hair and body hair,
and infertility.
Some also have genital differences
including undescended testes, the opening of the urethra
on the underside of the penis,
or an unusually small penis.
Older children and adults tend to be taller than their peers
and adults have increased risk
of developing breast cancer and lupus,
remember this is in males.
So their risk of developing breast cancer or lupus
is actually about equivalent to a normal females risk
for developing breast cancer and lupus.
Children may have learning disabilities
and delayed speech and language development.
They tend to be quiet, sensitive, and unassertive.
But personality characteristics vary greatly
among affected individuals.
Now, let's look at what happens if you have,
as a male, two Y chromosomes, XYY syndrome.
47, XYY, is what it would be designated.
This occurs in around one in 1000 newborn boys
and it's actually really unclear
if that's an accurate statistic
because many of them are never diagnosed.
Although taller than average, this chromosomal change,
typically causes no unusual physical features.
This is an image of a mother with her son
who has XYY syndrome.
Most have normal sexual development
and are able to father children.
This is associated with an increased risk
of learning disabilities and delayed development
of speech and language skills,
delayed development of motor skills,
such as sitting and walking, weak muscle tone,
hand tremors or other involuntary movements.
And behavioral and emotional difficulties are also possible,
though again it's a spectrum.
So some it may be more severe than others,
and some males, absolutely is expected
that there are many men out there
who will never be diagnosed with XYY syndrome
simply because it has given them no problems.
A small percentage of males with 47, XYY syndrome
are diagnosed with autistic spectrum disorder.
So there may be a link between this condition and autism.
So now, let's talk about what are the risks
for aneuploidy in the mother.
So we're looking at basically aneuploidy
which is occurring in an embryo.
So the risks are associated with,
the risks of this happening in an embryo,
are related mostly to the mother.
And as I mentioned with Down Syndrome,
advanced maternal age is a major risk factor.
Risk of aneuploidy increases significantly
for mothers older than 45.
In addition exposure to toxins and carcinogens
prior to conception can interfere in Meiosis
and lead to increased rates of nondisjunction.
Previous aneuploidy birth or spontaneous abortion,
many spontaneous abortions prior,
is associated with a higher risk
of subsequent aneuploidy birth.
It doesn't mean it's a given.
So if a woman has had, say, a child with Down Syndrome,
it does not necessarily mean her next child
will have Down Syndrome.
It does increase the risk slightly.
It increases the risk slightly.
But actually advanced maternal age
is going to have a much greater impact
on the likelihood of having a child with Down Syndrome,
than would having had a child previously with Down Syndrome.
Let's look at the difference between women and men.
So why does it seem like we're really
focusing on the risks in women?
Don't men also undergo Meiosis in order to produce sperm
and could it not happen in the sperm instead of in the egg?
Well, it certainly could and it does at times.
Nondisjunction in the egg is by far
the most common reason for aneuploidy.
Meaning that it happens far less often in the sperm.
And why is that the case?
Well, egg cells in females enter Meiosis
while still in utero.
Then are halted in prophase I
until puberty and ovulation when Meiosis completes.
So what do I mean by this?
A female embryo in utero forms the germline cells.
Remember those are the cells that will become gametes,
forms germline cells and basically initiates Meiosis I,
The very beginning stage of Meiosis I does not complete,
it just enters actually prophase,
that very first stage of Meiosis I,
and then it halts it and it stops it for a very long time.
It will stop it for about the next 13 years.
So those cells, those very same cells are just sitting there
in the ovary waiting of the developing girl
until she reaches puberty and until ovulation begins
when Meiosis is kicked back into gear
and those cells finish up Meiosis I and Meiosis II,
and then you have the mature egg cell.
So why is that a problem?
Well, it's a problem because these egg cells
build up mutations and toxin exposure over time,
which contribute to aneuploidy.
So over those 13 years,
that's the very earliest stage of ovulation,
say when a girl is 12 or 13 years old.
But you can imagine then,
the more advanced a woman becomes in her age,
the more likely that her egg cells,
which were formed when she was in utero,
are going to develop some problems.
And this absolutely happens just from normal exposure,
but especially from, you know,
if there are extra toxins or carcinogens
around those can speed up the process.
And she, if we're talking about a woman who's 40 years old
and she's going to become pregnant,
the cell that will become that egg is over 40 years old.
That's a really old cell.
Most of our cells in our body are turned over
regularly and rapidly.
Say within about a year or so,
most of our cells have actually turned over,
except for egg cells which are with us,
which are with females from the very beginning.
So as a result, these are older cells
and older cells are likely to have more mistakes,
are likely to have accumulated more mutations
and damage over time.
And as a result you have more issues that occur in Meiosis.
On the other hand, sperm cells in men
are continuously made fresh
and only start Meiosis when needed.
Meaning these cells are not as old
and less likely to have accumulated mutations and errors.
Sperm also compete amongst themselves
to reach the fertilized egg.
Damaged sperm cells are less likely to win.
So it's a kind of selection that happens
in the process of fertilization
because only really the strongest sperm
will ever make it to the egg.
So those that have damage or
issues that occurred during Meiosis
will probably never make it to fertilize an egg.
Let's take a quick peek at a
karyotype of an individual with aneuploidy.
I want you to take a look at this
and take a moment please to,
and I want you to take a peek at this.
Put the video on pause in a moment here.
And I want you to write down for yourself
what you think, what you would write up
as the karyotype designation here.
Remember karyotype designation would be
total number of chromosomes, comma,
sex chromosome designation, comma,
plus/minus, any autosomes that are in trisomy or monosomy.
So I want you to take a look at this, put it on pause,
and I want you to write, or I want you to think
of what that designation would be.
And even what these, if you can recall,
what the syndrome would be associated with this.
So you can put it on pause now and you can come right back.
Okay. Have you worked it out?
Well, it's Klinefelter syndrome,
which would be designated 47,XXY.
As you can see here, this individual has two X chromosomes,
which would be normal in a female,
except there's also a Y chromosome.
Y chromosome means this individual is male
'cause there's a presence of a Y chromosome.
Two X chromosomes means this individual
will have Klinefelter Syndrome.
All right, let's take a summary of
what we have covered so far.
Aneuploidy results from a nondisjunction event in Meiosis.
Remember nondisjunction is classified as
chromosomes not separating from each other properly,
in which paired chromosomes do not segregate properly
creating daughter cells with either too many
or too few chromosomes.
Most autosomal aneuploidy is incompatible with life
and results in spontaneous abortion.
Autosomal aneuploidy is far more severe
than sex chromosome aneuploidy.
Advanced maternal age, carcinogens,
and previous aneuploidy birth in the mother
increase the risk of aneuploidy.
But remember, that really it's about advanced maternal age
is the most likely culprit given the aging of the egg cells.
All right, well with that, what's next in this module?
So we'll follow this up with discussion
of other chromosomal abnormalities.
And these are going to be instead of at the scale
of an entire chromosome being present or absent,
this would be of a disorder in a chunk of a chromosome
and how that can result in some clinical manifestations,
which we'll discuss.
And then we'll follow that up
with a discussion on mosaicism.
All right, well please let me know
if you have any questions on aneuploidy,
and I look forward to speaking with you in the next lecture.