All language subtitles for 57031x_MH_Mapping_Linkage_01_Parentals_Crossovers_v-en

MICHAEL HEMANN: Today we're going

to talk about linkage analysis.

And this involves identifying where a particular gene is

on a chromosome.

So we've localized to chromosomes in the past,

now we're localizing genes relative to one another.

So why do we want to do this?

Why do we care?

Well, this is actually what geneticists do.

We actually try to start from phenotypes

and map the locations of genes.

And by localizing these genes, identify the genetic causes

or underpinnings of phenotypes that we're interested in.

So for example, we can talk about genetic variability

in populations and why some people are

more susceptible to COVID than others.

And this kind of study has been done recently,

and we'll talk about this in a few lectures,

and you'll talk about this kind of work

later in the semester with Olivia Corradin talking

about genome-wide association studies.

But it's the way that we go from something

that we see to an actual molecular detailed picture

of what is the etiology of this condition.

It allows us to identify genes and alterations in genes,

and ideally identify therapeutics

that we can use to actually affect or correct something

that we see as a defect, or in somebody that's resistant,

for example, to COVID, can we identify there a therapeutic

that would help other people?

So mapping is really essential and really is

the bread and butter of what geneticists do.

So we're going to talk about this, basically,

in the next four or five lectures.

And so we're going to start, as we frequently

do, in a model organism that we're comfortable with here,

talking about Drosophila.

And so here I'm showing Drosophila chromosome

schematized.

Previously we've mapped genes onto particular chromosomes,

like the X chromosome.

But what if we actually want to map genes on the X chromosome

relative to one another?

We want to figure out basically how far they are away from one

another so we can start building a map where all of these

loci, or are all of these places that are demarcated.

And so if we have a new gene, we can localize it

next to these locations, these phenotypes,

and identify what is the cause of alteration or mutation

underlying these alterations.

So say we have two alterations on the X chromosome.

So we can write in here genotypes and phenotypes.

And our X chromosome genotypes can be, for example,

if we're looking at two genes, one is white eyes,

or the mutation causes a white eye phenotype,

and the other is mini wings.

So white eyes and little wings, these

are the things that Drosophila biologists think about.

So if you are w plus and m plus on the X chromosome,

you're wild type.

If you are w plus and m minus, you have mini wings with wings.

If you are w minus m plus, you have white eyes.

So three phenotypes that we can--

two phenotypes and a lack thereof that we can clearly

see in male flies.

So let's do a little cross.

And so we'll start with a white-eyed male.

And we'll cross to a mini wings female.

So w plus m minus w plus m minus on both chromosomes.

And so the progeny from this cross, if you are a female,

the females are going to be heterozygous at both

of these loci.

So they're going to have one allele that's w minus m plus

and one allele that's w plus m minus.

We can take this female, this double heterozygote female,

and cross to a wild-type male.

And we'll do this just to see the interactions of the two

chromosomes in this female.

So we want to know, are these two alleles

staying together or are they moving away from one another?

Is there recombination that's occurring?

So from this cross, we essentially

get two categories of male flies.

So one of them--

category will have w minus m plus or w plus m minus.

And this we'll call parental.

And we'll call it parental because the alleles here

are the same alleles that we see, essentially,

in these parental types above.

So they're suggestive that there's no recombination here,

that they've stayed together on the same chromosome.

They're on the X chromosome.

So they haven't moved apart from one another.

Alternatively, we can get different classes.

And so one of the different classes that we can get

is w minus m minus, or w plus m plus.

So something's happened here.

There's been some reassortment of alleles.

And so we call these recombinants or crossovers.

Because they're not represented in the parental class.

So we can enumerate the relative ratios

of these parentals versus these

recombinants, or crossovers.

And so if the number of parentals

equals the number of crossovers or recombinant,

then we call these loci unlinked.

So this is the characteristic of independent assortment.

This is what we would see if they

were on different chromosomes.

So if the parentals exceed the number of crossovers,

and we say that they're slightly more,

then we'll say that these are weakly linked,

meaning that they are on the same chromosome,

but they're probably some distance away from another.

So finally if we have many more parentals, then the crossovers,

we'll say that they are tightly linked,

that they really don't move away from one another.

And in fact, when they're really, really close together,

crossovers may not appear.

If they're really, really tightly linked,

these crossovers are going to be really, really rare.