All language subtitles for 47031x_MH_Chromosomes_Mitosis_Meiosis_04_Aneuploidy-en

MICHAEL HEMANN: So what happens after a nondisjunction events?

Well, in general aneuploidy meaning

having a non-normal chromosome number is not tolerated.

So one in 800 live births has trisomy 21,

which is Down syndrome.

And Down syndrome is really the only aneuploidy,

is the only abnormal chromosome number

for an autosome that is reasonably tolerated.

So people with Down syndrome can grow and have a long life,

but other trisomies are generally not tolerated.

So trisomy 13 and 18 are viable, but they don't survive.

So in general, these kids are not born.

And if they are born, generally live less than a year.

Haploidy for autosomes is not tolerated.

So nobody is born with only a single chromosome,

a single autosome.

These are all embryonic lethal.

We actually in humans, we need two copies of every chromosome

and rarely, rarely, rarely can tolerate

three copies of a chromosome.

There are a lot of interesting explanations

in terms of dosage, appropriate gene dosage underlying

the reason why this may occur.

And there are also explanations why trisomy 21 may be viable.

I mean, it's the smallest chromosome, so, perhaps--

or it may have the most minimal effect along

with chromosome 22, but those are somewhat--

I think still somewhat speculative.

So we do tolerate some changes in the numbers

of X chromosomes.

So you can survive as an XO, so an X chromosome and no Y

chromosome.

This is called Turner syndrome.

You can be XYY.

So you can have two Y chromosomes.

People used to think that this actually

led to a predisposition for committing crimes.

I think that's been disproven to having too many Y chromosomes,

but it was actually argued for a very long, long time

that it makes people more violent.

XXY is Klinefelter syndrome.

You can be XXXY.

You can be XXXXY.

So you can tolerate increased numbers of the X chromosome.

Many sense for why--

yeah, there's a question what is the difference

between viability and survival.

Essentially I think they can be used interchangeable.

In the case of trisomy 13 and 18, in this case,

they can be born.

So they can reach embryonic maturity.

They can be born, and ostensibly most of the organ systems

are appropriate, but many of them

have serious, serious problems.

And so these kids, again, really never

survive to one year of age.

So by survival here, I mean durable survival.

So it's almost always associated with early lethality, which,

of course, is a really difficult thing for parents.

So there's a lot of embryonic testing

to look for the status of trisomies, particularly

these trisomy 13 and 18 that can lead

to really devastating consequences for children.

So why is it that you think we can tolerate larger

numbers of X chromosomes?

Yeah, so it's because of this process of X chromosome--

well, there's-- yeah, you only express one X in general,

right.

So there's this process called Lyonization or X chromosome

activation where one of the X chromosomes

is largely transcriptionally silenced.

And so for people that have two or three or four X chromosomes

generally have one or two or three

of these actually silenced so that you only

have expression off of one, and you can essentially

regulate dosage.

And dosage compensation in the sex chromosomes

is a really interesting thing, sort of,

how that works overall.

So lastly, let me just introduce this issue of aneuploidy

and development, and let's think about having a gamete that

has two chromosome 15s, right.

And this would be from a male, and then we

have a female gamete that has the appropriate just

one copy of chromosome 15.

You'd have fertilization here.

You have a resulting embryo, and this resulting embryo

has three copies of chromosome 15, right.

Now one of the ways that this can

be dealt with during development to actually result

in a viable offspring-- because trisomy 15 does not

result in a viable pregnancy-- is that you can actually

lose one of these chromosomes during development, very early

in development actually, right.

So you can get three different possible offspring,

one with two chromosomes from dad

and the other with a chromosome from dad and a chromosome

from mom.

Do you think it matters which of these outcomes exist?

Any guesses?

Yes?

No?

Two possibilities?

It does matter actually so.

If you have two chromosomes from a parent, a father or a mother,

you had what's called uniparental disomy, right,

meaning you just got two chromosomes,

disomes from one parent, right.

And this matters in the context of a number of conditions

called imprinting disorders.

Now interestingly, you have differential gene expression

depending upon the alleles that you inherit from your mom

or your dad for some genes, a subset of genes,

probably less than 50 genes in people.

And so sometimes a gene that you inherit from your father

is turned on, but the maternal allele is turned off, right.

And so if you have two genes that are turned on

or two genes that are turned off,

you have what's called an imprinting disorder, right.

And in the case of chromosome 15,

you have Angelman syndrome, which is actually

a very severe syndrome that has a number

of different phenotypes.

So the genes that you inherit from both your parents

are actually differently regulated.

You need to actually have a maternal and a paternal allele

to have appropriate dosing in the embryo.

And there are lots of really weird explanations,

anthropological explanations for why males and females have

different genes off and on.

There are ideas of sexual antagonism

that are from fly studies, and I'd

be happy to tell you about some of these

if you're interested, but know this does occur.

So on Wednesday, we're actually going

to start talking about this issue of recombination

and how we can link two genes together and think

about how this is occurring in meiosis

and how we can use this to actually map

the fine location of different genes.