All language subtitles for 47031x_PR_Mendelian_Genetics_04_Mystery_Revealed_v3-en

PETER REDDIEN: OK, so we could then

say that we have a gene that is important for the results

of our crosses.

We'll name this gene.

We'll call the gene paralyzed.

So that would be our gene name.

And then we will consider there to be two

alleles of this paralyzed gene.

So I'll just shorthand for this gene, call it para.

And there will be a para superscript wt

allele, and a para superscript ts allele.

OK, so those will be our gene variants

for the gene paralyzed.

OK.

So now we can think about these two alleles with respect

to our crosses that we've done.

And the idea is that the parents are contributing alleles

to the offspring where there will be a sperm

allele and an egg allele.

So we'll have one allele from each parent of a given

gene that combine in the offspring,

and the offspring will have two alleles

and it will be a diploid organism.

So now we could look at our same crosses

that we described earlier.

Instead of denoting phenotype, we'll

denote these genes and their alleles and some notation

and this will be the genotype.

So we'll draw these crosses again,

but now considering genotype.

So in our first cross we have a para ts over para ts fly.

So we're going to propose that this was its genotype.

And you'll see why as we go through the crosses.

We propose that it has two copies of this para ts allele

and that what we did was we crossed it

with a para wild type over para wild type fly.

OK.

Now this paralyzed gene is a real gene,

and there are real mutant flies that

have mutations in this gene, and I have some with me.

So you probably have been wondering

what this microscope is for.

I'm going to try to show them to you.

We'll see how this goes.

So ts stands for temperature sensitive.

And it is a temperature sensitive allele

meaning it only confers its phenotype

at certain temperatures.

So here's some control flies.

They're wild type flies.

They have a lot of nice attributes for genetics.

You can see their red eyes there,

cruising around, very good.

OK.

So now what I've told you is words is that this ts allele,

it's a temperature sensitive allele.

So now I need to heat these flies up.

First I'll do my control experiment here.

So I have a heat lamp.

I'm going to shine the heat light on these wild type flies.

And so at 20 degrees, the para ts over para ts flies

can move normally, but at 29 degrees,

they should get paralyzed.

Let's see if this works.

So first I'll just show you that not just

cooking these flies here, I'm heating up the wild type flies

and we can see they're still flying around.

Wild type flies, I don't know if they like the heat,

but they don't seem to care with respect to their movement.

Good.

Now the para ts flies, we'll start with no heat here.

You can see they're flying around.

All right, so now let's shine this light at these flies.

OK.

All right, you see these guys starting

to flop down to the bottom?

All right.

They started all collecting at the bottom here,

I can shake them.

They're not moving.

They're totally paralyzed.

OK?

Now-- so it worked.

Now don't worry, the flies are-- this is a reversible phenotype.

So if we shift it back to 20 degrees--

it'll just take a minute--

the flies should wake up and start moving again.

Starting to see them perk up again.

OK.

So you see them waking up-- waking up?

Yeah, they're looking better.

They'll be flying around in a couple of minutes.

There we go.

So this, as I said, is a real gene called paralyzed.

What does it do for the flies?

Well, it encodes a sodium channel,

which exists in the neurons of the fly,

and this allows sodium in for carrying electrical activity

in these neurons.

The ts allele is one nucleotide change

in 180 million nucleotides in the genome of the fly.

One nucleotide change that leads to this phenotype,

that nucleotide is in the gene encoding this paralyzed

protein-- the sodium channel--

such that at high temperatures, it

can no longer function for letting sodium through.

And you could start thinking about why would it

matter whether you had one copy of the para ts allele

or two copies of the para ts allele in these crosses?

But the other thing I'd mention is

there are similar genes that control important attributes

of biology across organisms.

So we, too, have a paralyzed gene--

this sodium channel gene.

And it's functioning in our nervous system

to control electrical activities.

And we'll see this as a theme over and over

again that there are genes that exist across organisms that you

can study in one organism and learn about them in others.

I mentioned that we have a version of this paralyzed gene,

the human version of the para ts gene has this name--

sodium subscript 5 1.7, or SCN9A.

And it's a voltage-gated sodium channel.

OK, so I also mentioned that there

are people that have mutations in this gene

and you can see some data here from a paper where

these are pedigrees.

We'll get into pedigrees later.

Just suffice it to say the filled-in circles and squares

are individuals that show a trait.

And this trait was that the affected individuals

couldn't feel pain.

It's a pretty interesting phenotype.

In some ways, it sounds like some kind of superpower

where wouldn't it be great to not feel pain?

Of course, sensing pain is pretty important to not getting

injured.

But nonetheless, it triggers ideas.

So if you could block the functioning

of this channel in some way, maybe

that would be useful in certain circumstances,

like surgery or other things.

And people have been working towards that

to try to see if they could manipulate

the functioning of this protein with molecules

to try to have some types of therapeutic approaches.

There is nothing working yet, but it

will be interesting to see what unfolds.