Welcome to the next lecture on Mendelian genetics.
We have been talking about the use of Mendelian principles to analyse inheritance especially
toward prediction of the occurrence of a (certain) of some inherited disease in an offspring,
so that the parents would be able to handle it better.
Let us look at a person affected with a genetic disease. Suppose a person is affected with
a genetic disease. What are the chances that a child will be born with that disease? That
is a question that we are going to ask now, okay? In this lecture this is what we are
going to see the various possibilities of that happen. To do this, something called
a pedigree analysis can help. Pedigree charts or family charts show the family relationships
over history and phenotypes characters, characteristics. So based on the phenotypes the characters
the observable characters, the genotypes are worked out as completely as possible and used
to make further predictions, okay? We cannot go and do experiments with humans and therefore
we need to use all the information that is available in terms of observable characters
and draw our conclusions. Of course if it is if somebodyÕs genotype can be tested,
just by taking some part of the saliva or some blood and so on and so forth, that can
be done. That is that is acceptable to most and that can be used to help in the analysis.
However in many of these cases it may not be even be possible because maybe the grandparents
and the previous generations have passed on and therefore the analysis of the phenotypes
and the guess of the genotypes are used to get as complete (inf) an information on the
genotype as possible and thereby make further predictions. We will see a couple of examples
of those. For that you have a certain terminology, if
we have a circle it means a female, if you have a square it means a male. These are standard
terminologies for Pedigree analysis. If you have a filled square it means that the female
has the disorder, the disorder is apparent; if it is a filled square it is a male with
the disorder. If it is a half-filled circle then something called a female carrier, it
will become clearer, if the person does not show the disease with (the) person carries
a part one allele which can cause the disease. And this is true for recessively inherited
traits, you know, if both need to be small, let us say small p small p for a decease to
manifest, then if it is capital P small P then this becomes a carrier, right? The small
P is still there, that can be passed on to the next generation although because of the
capital P this disease may not manifest in this particular person in the carrier. That
is what the carrier means. The disease is not manifest but the person has a potential
to pass on the allele to cause the disease in the offspring, or in the offspringÕs offspring.
And this is a male carrier. So circle is a female, square is a male, if it is filled
than the person is showing the disorder, if it is partly filled then the person is a carrier,
okay? These 2 can be you know, filled in or these 2 can be decided just by observations
and records, whereas this requires a genetic analysis or a at least genetic possibilities
which we can deduce with surety.
Let us take the case of a recessively inherited disorder, okay, which is what would be natural
to think if it is both small then the person has the disease, that is not always the case
but (in) let us, let us take that for the time being, that is what would be, that is
what one would expect given the background that we have been through.
Albinism, you know the person withÉ who has light coloured skin patches, skin patches
or sometimes even the entire body that is albinism, okay? That is recessively inherited
disorder. Let us say that this is a family that we are considering. A female who has
albinism marries a male without albinism and they have children. A female without albinism,
a male with albinism, a male with albinism and a male without albinism, and these 2 marry
and they produce 2 children, a female without albinism and a female with albinism, okay?
Then these 2 marry, these are 2 different families, their children, the 2 among their
children, each one, a child from each family marries the other and they have children.
So far the observations are one has albinism, is a female with albinism and another is a
female without albinism and this is the grandparents generation, the first generation terminology,
this is the parents and their siblings, okay, the second generation and this is the third
generation that we are currently concerned with this is what it is and this is the family
tree on which we are going to do pedigree analysis.
If we are interested in finding the following, if another child in the third generation,
in this generation is born to the same parents, what is the probability of that child being
an albino, okay? Here itself is I mean, by now it is not very surprising, but to see
here this person is not affected with albinism, this person is not affected with albinism,
whereas the offspring of that those parents is affected with albinism. That is because
it comes from the grandparents, okay? Now that we know Mendelian inheritance, we know
how this can happen, the recessive possibility- it is skipped here whereas it is manifested
in the third generation. Let us go back to theÉ let us go to the analysis
now. This is the way the various linkages in the family are shown and the various phenotypes
are shown according to our code, the generally accepted code. If we look at obvious genotypes,
this is a male with albinism therefore it has to be small p small p, or anything with
an albinism has to be small p small p because it is a recessively inherited disorder.
So let us start here small p small p, small p small p. This one should also be small p
small p, that we can fill in for everything. Whereas here the person does not have, itÕs
a female who does not have albinism, okay, whereas this parent has both small p alleles
and since one allele comes from each parent, definitely one of the alleles has to be p.
And since this person is not showing albinism allele has to be capital P. If the other allele
had been a small p then this person would have also been affected.
Similarly, this person is from this parent therefore must have inherited a small p, and
this, the other allele must have been a capital P from the other parent, okay? With this,
and taking a look at this, this father or the grandfather should have had at least one
capital P and one small p. Only then these kind of possibilities would exist, right?
(Otherwise) if both had been capital P then these 2 people would not have had albinism,
theÉ both the other allele would have been capital P and as long as one allele was capital
then the disease would not have been manifested here. And since it has manifest here and also
it has not manifest here this person must have had capital P, small p, okay? This is
the analysis. Similarly we can do an analysis here. This
is small p small p definitely, this isÉ and this is small p small p. These both are affected
and this must have been capital P because this person does not have the disease and
therefore it is quite easy to see why this mustÉ must have also been capital P small
p because the person does not have the disease. Now this is heterozygous, this is also heterozygous,
it is a cross between heterozygous parents and what is their probability that this person,
whether male or female would have the disease. It would be one fourth the probability you
know these (are) these are heterozygous cross, therefore capital P capital P, capital P small
p, small p capital P and small p small p are the possibilities, therefore one fourth is
the (probability) probability that it will be small p small p, result in the child being
albino. We could also ask what would be the genotype of the third generation offspring
which is these 2 and quite easy to see it has to be either capital P small p or capital
P (spa) capital P, both can arise. We cannot rule that out from just this observation that
the person is not an albino. The person could be a carrier, okay? Whereas here it is very
clear that it has to be small P small P, okay? So this is lot of information that we can
gather just by looking at what the the various relationships between people and their observed
characters. And we have guessed the genotypes based on or deduced the genotypes that is
the best way to say it, deduced the genotypes, given that albinism is a recessively inherited
disorder, okay? Now, some of you might have been wondering why did I keep harping on recessively
inherited, okay. You (can) you could think how else could the disorder be inherited.
It so happens that a disorder could be a dominantly inherited disorder too.
And HuntingtonÕs disease which is so prevalent in the US is actually a dominantly inherited
disorder which means if one allele is capital then the person has the disorder which also
means that most of the population is homozygous recessive, okay? Both are small small, right,
only then will the population not have (will) will the person not have the HuntingtonÕs
disease. If one of them is capital then the person definitely has the disease, that can
also happen. At the same time the dominant allele is not the one that is found the majority
of people, okay? This could also happen, we will not get into how it happens and so on
so forth. If you are interested you can go and read later chapters of your textbook,
it does talk about that.
But for now, basic course let us look at what happens if you have a dominantly inherited
disorder and let us do a pedigree analysis for the very same family, okay? It is the
same family so this is what it was, right? And these things refer to the HuntingtonÕs
disorder. By the way HuntingtonÕs disease or a disorder is a neurodegenerative disease
that sets in after 45, okay? So it is sometimes a little difficult for the people and they
could actually have their genes genotype tested to say whether they (are) to see whether they
have HuntingtonÕs disease. If they have HuntingtonÕs disease then it
is a badly degenerative disease that sets in after 45 and its bad life after that. So
it is it has a lot of ramifications social and cultural and so (on) social essentially
and of course health wise and the fact that you could be sitting on a ticking time bomb.
So it is one such disorder which is predominantly found in the US, not much in India. Here this
shows the family members who have HuntingtonÕs disease by a shaded square or a circle, okay,
a shaded square is (an) an affected male and the shaded circle is affected female, okay?
Now let us do the analysis here, the same way that we did analysis for a recessively
inherited disorder which was albinism, it was an example of that. Same question if (a)
another child is born to the same parents what is the probability for HuntingtonÕs
in that child, okay? This is more serious than albinism, albinism is merely looks and
maybe it it makes the person prone to cancer and so on, skin cancer but it is not as dangerous
as this, okay, but it has a social angle to it so that could also be considered in point
putting off. Very clearly this has to be both smalls for
the person not to show the disease, (s) both small here and both small here that can be
very easily guessed, deduced. Since this person is showing the disease and this is both recessive,
it has to be at least one dominant for the person to show the disease and therefore (it)
this has to be (s s) small h and capital H. This has also got to be small h capital H
same parents, and because this is small h capital H the only way this can result is
if this is capital H small h. This cannot be capital H capital H, otherwise these 2
people would have also had the disease. Similarly this would be small h small h, no
disease. This one would also be small h small h, no disease. This has to be capital H capital
H with the disease because this has resulted in one small h coming from here therefore
at least one is a small, the other one has to be capital for it to show the disease,
therefore it is capital H É. small h, and by the same argument this is capital H small
h. And what is the probability that this person
will (have) will have HuntingtonÕs, you can work at the probabilities here. Either if
one of (the) either if it is heterozygous dominant or homozygous dominant the person
will show the disease, so it is a very high three fourth or a 75% probability that the
(sib) that the child, born to the same parents will have HuntingtonÕs disease, HuntingtonÕs
gene which will develop into a disease at around 45 or so.
And genotype of the third-generation offspring is capital, small h (cap) small h here and
if you work out the details here we will not be sure. It would either be this and this
or this and this or this and this. Therefore it is either capital H small h or capital
H capital H. (One) at least one has to be capital because the person is showing the
disease. Okay, these kind of questions can be answered and the parents can be alerted
to these possibilities, the people can themselves be alerted to these possibilities.
Now let us look at both of them together, okay, and use probabilities here. If another
child of the third-generation is born to the same parents, what is the probability of that
child being an albino with HuntingtonÕs? Okay? Albino is 1 characteristic, Huntington
is another (character) character, they are independently inherited according to Mendelian
principles and to come up with the probability we need to consider a dihybrid cross in which
albino character and HuntingtonÕs character (is c) are considered. If we do that (invo)
invoking law of independent assortment, the probability of HuntingtonÕs is three fourth;
the probability of albinism is one fourth according to the various combinations here.
Therefore, the probability of an albino with HuntingtonÕs, okay, both are independently
inherited independent assortment, three fourth into one fourth (prob) multiplication rule,
3 by 16, okay, so this is the probability. So you can work out various different things
with these probabilities and the law of independent assortment.
One can get tested for the presence of disease genes and alleles whether you are a (ca) a
carrier or not. If you have the disease you know that your genotype could be a certain
way, if you do not have the disease you would like to know whether you are a carrier, whether
you are going to pass it on to the next generation, one can do that. Even foetuses can be tested
through (p) procedures called amniocentesis or chorionic villus sampling called CVS. These
2 are done, especially for disease kind of a situation and so on, okay?
Whatever we have seen so far is valid for a certain kind of inheritance. It is for the
inheritance of alleles that reside on the 22 pairs of human chromosomes. The 23rd pair,
XY if you recall, determines the sex of the child, okay, whether it is a male or a female.
And the 23 pairs are found in each cell in each body, that that you already know. Whatever
we have seen so far is valid if the allele sits on the first 22 chromosomes, not the
23rd. If it is, if it sits on the sex chromosomes, then things are going to be different and
let us see how the things become different, if the allele sits on the sex chromosome.
The first 22 pairs are actually called autosomes or somatic chromosomes, somatic for body,
somatic chromosomes. And the 23rd pair is called the sex chromosome because it determines
sex of the person. Now, gender I think in this lecture we would use interchangeably
with sex but in actual terms gender has a social connotation and sex has a biological
connotation but (we) we could use this, or I could use this interchangeably in this lecture.
The female has an XX sex chromosome occurrence and the male has a XY sex chromosome occurrence.
In addition to sex determining genes, there are many other genes that are present on X
and Y, the inheritance of characters determined by the genes present in X and Y is what is
called sex linked inheritance. If it is sex linked inheritance the probabilities would
be different from what we have seen if they had been autosomal inheritance.
An example of sex linked inheritance is haemophilia, haemophilia is an inability to inability of
the blood to clot and if that happens then the person has a wound then the person continues
to bleed. If it is outside, there is a way of handling it but if it happens inside then
it can be dangerous, the person can bleed to death for no fault. And that condition
is actually called haemophilia.
You can take a look at this youtube video, if it is a female it is XX and let us say
that the person has A and A (pheno) A and A genotype there, we are using a superscript
to determine the genotype, that is associated with the X chromosome. Since it is a male,
it has to be X and X and Y, since the male is affected it is a (capi) it is a small A.
The gametes from a cross between these 2 would result in Xa Y, X small a, Y, and capital
A capital A the gametes are XAXA from the eggs and the sperm gametes are Xa Y. And a
Punnett square from this kind of a cross would result in capital A small a, capital A, capital
A small a and capital A. And as you can see the, if there is a Y, the
offspring is going to be a male, both these are males and both these have the capital
A on their X chromosome so therefore they are unaffected. The female offspring, these
2 they are again unaffected because they have at least one capital A, but they are carriers,
they have the other small a, right? Therefore female offspring is a carrier, is not affected
but can pass on to the (it can) pass on the defect to the next offspring, this we have
already seen, okay, this is the way it happens. The probabilities would be different if you
calculate, it is (deter) it is dependent on the sex of the person, sex of the offspring.
Now let us say, it is a cross between a carrier and an affected male, carrier female and an
affected male. If we work out the Punnett square, it is going to be something like this.
The one female and one male are going to be affected, okay? Therefore 50% of the offspring
are affected this shaded ones are the affected ones, 50% of the offspring are affected. The
male offspring this and this are males, male offspring (again) again 50% affected and female
offspring, 50% affected and 50% are carriers.
Another example between a carrier female and an affected male; in this case only 25% of
the offspring are affected, it happens to be a male because the small a comes here,
the Y does not have anything, the (male) if you consider the male offspring alone, 50%
are affected. If you consider the female offspring alone, no female offspring is affected but
50% are carriers which are these, okay? So if the allele (rests) lies on the X chromosome,
then the probabilities are going to be different from that we found with autosomal disorders,
or the alleles that reside on autosomal chromosomes.
Thus X linked inheritance is different from inheritance by Mendelian principles. Pedigree
analysis with Mendelian principles that we saw earlier can be extended in some situations,
such asÉ. X linked disorders, okay, to a certain extent. This is one such possibility
that have shown here, what I would say is why do not you work this out we have already
been at it for about 30 minutes or so, a long lecture; why donÕt you work this out with
whatever we have learnt in this particular class and when we begin the next class I will
begin by solving this, okay, there are these question marks here, this is what we need
to find whether these are affected or not, that is the question. These are various numbers
that are given for our reference. The other representations are the normal representations
and these 3 are affected.
You would like to find out what kind of a disorder it is it ya these are the questions;
is it, is the inherited character dominant or recessive, autosomal or X linked; that
is the first question. If 3 is not a carrier, if this is given, what are the genotypes of
1 and 4? That is what you are asked to find. The probability that 14 is affected is what
you are asked to find, okay? Why donÕt you work this out and then when we meet you can
check the solution with the solution that I will provide in the next lecture. See you
then.