All language subtitles for 47031x_PR_Human_Mendel_Genetics_01_Decision_Tree_v1-en

PETER REDDIEN: Let's move forward then

to human Mendelian traits, part two of the lecture.

All right, so here's our idea.

At this point, we've looked at pedigrees,

and we're going to move forward with pedigrees

and try to use them to identify the genetic basis of diseases.

So let's just start at the beginning

here and say we have some trait or disease.

What is our real goal here?

Our real goal is to find the cause.

If we know the cause, there's something

we could do to intervene.

The first question we might want to ask is, is it genetic?

And let's say we find that it is.

There is some genetic basis for it.

What we're going to be doing is to try

to go from this information that it is genetic

in some way with human populations

to find the gene or genes involved.

OK, that's going to be our goal.

Now, how would we know if something is

genetic in human populations?

Any ideas?

So we're going to-- we can look at pedigrees.

So that's one suggestion.

And that can give you some information.

We're going to come back to that.

But that will only apply to certain cases.

There can be a genetic--

there can be genetic basis for traits

where you don't see a clear inheritance

patterns in pedigrees.

So that wouldn't be a definitive way to know.

So any other ideas?

OK, looking at the genome of everyone

affected and see if you see something in common.

OK, I'm going to come back to that.

That is doable.

It has some limits.

And the core part of the limit is

that there's 3 to 5 million variants, sequence variants,

between any two individuals.

And so there's a lot to sift through.

The genome is 3 billion bases, 3.2 billion bases.

So, somewhere in there is, if it's genetic, we think,

is what's causing this trait.

So that's the trick.

That's the challenge we have before us

is, how do we sift through these 3 billion bases

to try to actually find it?

Now, we talked about some concepts

of how to do that in organisms where

you can study it in the lab.

And I'll mention this again as we go through.

But here we're just stuck with what has

happened in human populations.

OK, so any other ideas to determine

if something is genetic?

You can try to study and look for alternative hypotheses

and see if you find support for those.

Yeah?

STUDENT: Wouldn't it be possible to do a twin study?

PETER REDDIEN: OK, twin studies.

OK, twin studies are very useful for determining

if there's a trait that's heritable

where identical twins, monozygotic twins,

share 100% of their alleles, whereas dizygotic twins,

fraternal twins, share 50% of their alleles.

So you can compare those two, though, they're in similar--

you can hope-- similar environments

and try to distinguish the genetic

from the environmental causes.

So that's a powerful way to do it.

I'll leave it at that for now.

We may have more to say about that later.

OK, so let's say we have some information that something

is genetic then.

So, yes.

The next thing we want to know is, is it

Mendelian or a simple, single-gene inheritance

pattern?

Do we see an autosomal dominant type of pattern?

Do we see an autosomal recessive pattern?

Sex linked?

So, often, the answer is--

often, the answer is no.

The twin studies tell you it's genetic.

But you look at the pedigrees, and it

doesn't look to be a simple Mendelian inheritance pattern.

And that's what I kind of alluded

to at the very beginning in the class

that, often, a lot of traits and diseases

are complex where there's many genes contributing.

So examples are height or schizophrenia.

There's many, many examples where

you see a high degree of heritability,

but you don't see it tracking through pedigrees

in a very clear way.

OK, we're not going to deal with these now.

These are for later in the class.

But we will come back to how to try to crack

these kinds of cases too.

There are genetic ways to do that.

For now, where we are in the class,

we're focusing on Mendelian, so scenarios

where, yes, we see some kind of Mendelian pattern in pedigrees.

OK, all right, so now our goal then-- so now the answer

is yes.

We know it's Mendelian.

Now, we want to find the gene.

OK, so how are we going to do that?

It has been done many times.

It is possible.

So how are we going to do it?

What do you guys think?

We've had one suggestion already.

So one suggestion was sequence.

Sequence the individuals in the pedigree.

And I've talked about the challenges

there that there's a lot of variants to sift through.

Nonetheless, there are some approaches

with sequencing that can be done.

And I'll get into that in a moment.

Any other ideas?

Great, that's it.

We use linkage information.

OK, recall, that's how we've done it already in this class.

You've seen how, in, say, the Drosophila X chromosome,

you could figure out the miniature wing

locus, what it's between.

And then we extended upon that to take sequence information

and use polymorphisms to get map distances

between some gene causing a trait and some polymorphism.

The polymorphisms, we know where they are.

By definition, they're sequence variants in the genome.

And so that's what we're going to do here.

OK, so we're going to know the pedigree.

We can take advantage of these variants that

exist between individuals.

And what we're going to do is we're

going to ask which of those variants

segregate through a pedigree together

with whatever mutation is causing the trait.

And, if we can find which ones go together,

then we'll know where in the genome

our disease-causing gene is.