All language subtitles for 17031x_MH_Mapping_Linkage_06_Considerations_v1-en

MICHAEL HEMANN: Now, this kind of mapping, again,

is based on crossovers between two different genes.

And so let's think about that just a little bit more.

So say we have A1D, A2+, A1D, A2+.

And we have A1+, A2D, and A1+ and A2D.

And so if we have a single crossover--

and we'll look at crossovers per interval, the interval

here being the space between A1 and A2

and whether we get recombinants.

So, if you have one crossover, you

get recombinant because you get A1D and A2D put together.

But imagine if you had a second recombination event

between the same two alleles.

So one occurs, and then it flips back.

Do you have recombinants at this point?

Or maybe I should say, do you see recombinants at this point?

You do that it occurred, but you're not going to see it.

If you have two events, you won't see it

because it flipped once, and then it flipped back.

And so you can think, OK, if I had three,

then you'd see it again.

If you had four, you wouldn't see it.

So, if there's an even number of flipping events,

things are just going to flip back.

And they no longer are recognizable as recombination

events.

And this occurs naturally the longer

that they are away from one another

because there's, essentially, more space

for these recombination events to occur.

And so we can think of this in terms of what we call

sort of a mapping function.

And, if we look at the relationship

between genetic distance and physical distance,

we'd expect, theoretically, that this would be

kind of a linear relationship.

The bigger the genetic distance, the bigger

the physical distance.

But this isn't the case when you get to larger numbers.

So they track together for a little while,

but the appearance of these different crossovers,

1, 2, 3, 4, obscures the overall genetic distance.

So it falsely, essentially, decreases the genetic distance

because you're underestimating the total number

of recombination events.

And the place that this really breaks down

is at 50 centimorgans.

So 50 centimorgans or below 50 centimorgans

is really the upper limit for any relationship

that we can interpret between two distinct alleles.

And it makes sense when you think

about recombination rates.

So, if the number of parentals equals

the number of crossovers, essentially, this

occurs at 50% recombination, so a distance

that would be 50 centimorgans.

And this is the hallmark of independent segregation.

So we can't differentiate between--

so 50 centimorgan would be any organism because here we're

looking at a genetic distance.

So the actual physical distance would

vary in terms of what that upper limit is

between different organisms.

But, here, all that 50 centimorgans means

is that there's a 50% recombination

rate, that 50% of the gametes are crossover gametes.

And that's exactly what you would

expect if you had just random assortment

of different chromosomes, if they were placed

on different chromosomes.

So there's a point where we can no longer

infer any meaningful relationship between these two

alleles.

And that point is really under 50 centimorgans.

And, even below 50 centimorgans, this

is really breaking down because of this issue

of multiple crossover events.

So this presents a problem to us if we have,

essentially, a sparse phenotypic landscape.

So, if we don't have that many phenotypes to follow

and we're trying to identify and finely map different places--

or different alleles on the same chromosome-- and this

is definitely the case when we look at humans.

The space in the genome far exceeds

the number of phenotypes that we can actually really even look

at.

Then we actually have to have another metric

to be able to link things together.

And so what that metric is are the use of DNA markers

and the use of things like SNPs, or Single-Nucleotide

Polymorphisms.

And these markers that we'll talk about

are going to allow us to do really fine mapping in lots

of different genomes, including the human genome,

so that, not only can we place phenotypes together,

we can actually place genes next to markers

that demarcate particular places in the genome.

And so, essentially, all of the mapping

that we're going to do in the future

relates to the use of markers, DNA markers,

in addition to the phenotype or phenotypes

that we're interested in looking at.