All language subtitles for 37031x_MH_Inferring_Patterns_03_Autosomal_Rec_v1-en

MICHAEL HEMANN: OK, let's look at another pedigree.

So what do we think is the pattern of inheritance here?

Do we think it is dominant?

Do we think it is recessive?

Do we think it's X-linked recessive?

Yeah, we're getting a couple answers, recessive.

And that's, in fact, the case.

And so there are really characteristics

of recessive conditions.

One of them is that you have affected children that

don't have affected parents.

So we saw that there was that ratio between affected parents

and children in autosomal dominant conditions.

We don't see that in these conditions.

It's unlikely that this is a de novo new mutation because we

see multiple individuals in this family that are affected.

So we can sort of rule out the idea

that these are just spontaneous new mutations because they're

occurring frequently.

They're not occurring in parents,

so it suggests that maybe we're homozygousing alleles.

And then really telltale signs of these conditions

are shown here.

So these are consanguineous relationships, right?

So basically they are mating between two family members.

You know, so cousins or somewhat more distantly

related, or possibly brother/sister.

So these are characteristic of recessive conditions.

And so we can think about how this actually occurs

and why this occurs.

OK, so if this is a recessive condition,

then we imagine that the parents of all

of the affected individuals are actually carriers.

So we can fill in these dots here.

Here's a carrier.

Here's a carrier.

Right?

Here's a carrier.

Here's a carrier.

And very likely in this family, this mother is a carrier

and this father is a carrier.

And this mother is a carrier.

Right?

And in this first generation, we have either the matriarch

or patriarch here that is very likely a carrier.

Right?

And so consanguinity here is really

important in the generation of this condition

because it provides a strategy whereby example,

or for example, a single allele that's

present in this guy years ago can actually

become a homozygous allele if you actually have inbreeding.

Right?

So this allele is passed on.

And in most cases, that single allele

would not actually lead to any phenotypic effect in a larger

population, as it's segregating just as a single allele.

But in a smaller family, that allele,

if it is homozygoused through the interaction of people that

now have this much higher allele frequency in the family,

can lead to the appearance of a condition

that typically you would not see.

So again, this is really characteristic

of recessive conditions.

So for autosomal recessive conditions,

we have a couple rules.

And that is, if both parents are carriers,

one quarter of the children are affected.

And when both parents are affected,

all children are affected.

And finally, if the trait is very rare,

then consanguinity is likely.

Now, consanguinity doesn't always

occur in recessive conditions.

For example, here we're looking at a pedigree

for the cystic fibrosis condition, which

is a very serious respiratory condition characterized

by chronic infections and, essentially, mucus accumulation

in the lungs.

It is characteristic of a number of populations,

or endemic in a number of populations,

including French Canadians, and here,

Ashkenazi Jewish populations.

This is actually one of the first conditions,

along with Tay-Sachs condition, where

there was genetic testing that was performed.

And it was really prompted by a huge desire in the Ashkenazi

Jewish population in New York to identify who is affected,

who are carriers to try to give counseling

and instruction to potential parents,

potential partners to tell them, are you both carriers

or do you want to consider being with somebody that's not

a carrier so that you actually decrease the risk of having

affected children.

It is not, in this case, caused by inbreeding per se.

It is caused very likely by a founder effect,

having a small population of people

in which these allele frequencies are really high.

And so we'll talk about founder effects and allelic segregation

with populations later in this class.

This is an interesting biology.

So of parents, so for documented carriers of cystic fibrosis, so

if both parents are documented carriers,

what would you expect the frequency

of having a child having cystic fibrosis would be?

Both parents are carriers, right?

So absolutely, you expect it's a quarter.

It's actually a third.

So one out of three children of documented,

verified cystic fibrosis carriers,

one third of the children are affected.

Why is this the case?

We have a CF child, right?

So lots of people in the world that are carriers,

or partners that are carriers for CF that have children that

are unaffected three quarters of the time

may never actually get genetic counseling.

They may never go and see whether they're carriers.

Only people that actually have kids that have a condition

are going to be tested for carrier status.

So those numbers are intrinsically

going to be skewed, based just on human behavior.

And this is something really to bear in mind when you're

thinking about hypotheses and patterns of inheritance,

that it involves science and it involves genetics,

but it also involves human nature and the ability

to assemble meaningful pedigrees to get accurate information

from people.