Welcome to the next lecture on Mendelian genetics.
This will most likely be the last lecture on Mendelian genetics. We said that many diseases
are genetically linked and to (ha) usefully analyse such disease inheritance,
we could use Mendelian principles. We showed some examples, we looked at some examples
and then came to the situation of X linked disorders, the disorders that arise due to
alleles that are inherited from X linked chromosomes. We saw how the inheritance patterns could
be different from those predicted by Mendelian principles and said that you could work out
this example and we would start this lecture by solving this example.
This is a a family tree parents and then the 3 offspring here, they marry and they have
children and there is one more generation that is occurring here and after mating here,
there are children here and we are trying to answer some questions related to these.
The first question was; is the inherited character dominant or recessive, is it autosomal or
X linked; that is the first question. The second question was; if 3 is not a carrier
as, that is given (sam) probably the person has genotypic analysis (re) analysis results
and (no) we know, we know that the 3 is not a carrier of the disease. If that is a case,
what are the genotypes of 1 and 4; that is the second question. The last question was
that what is the probability that 14 is affected, okay?
So let us look at how to solve this. As you can see this disease misses a generation completely;
4, 5 and 7 (who) who are offspring of 1 and 2, is completely missed here, okay? If it
is dominant, then this kind of a missing will not arise because one of the, as long as one
of the genes is dominant the disorder will manifest. Therefore it is most likely recessive,
right, since it has missed a generation that will happen only if it is a recessively inherited
disorder and if you see here only males are affected, 2, 8 and 10 are affected, all are
males and that will happen most likely if it is X linked, okay? Therefore it is a recessive
disorder and it is most likely X linked. Now let us try to answer this question; if
3 is not a carrier what are the genotypes of 1 and 4. We know that it is a recessively
inherited disorder and most likely X linked so let us work it out. This person has to
be X capital A, X capital A or a heterozygous person, X capital A, X small A, the person
is not showing, it is recessive therefore even this kind of a genotype will not result
in the disorder being manifest. And this is manifested here and it is X linked therefore
this has to have a recessive allele on the X for it to be manifest in this male here,
okay? So it is X small a Y here. We are (the result) we are interested in 1
or 4 so far on this 1 could either be this or this is what we can say. Let us look at
8 here. This is an affected person therefore it has to be X affected male therefore there
has to be a Y chromosome and it is X linked therefore the (X) the disease allele needs
to be carried by X, X small a Y. We know that this person is not a carrier
therefore X capital AY, male and the (possible) this person is a female and not affected since
it is a female it has to be XX. Since person is not affected and the father is affected
this would be an X small a and the other one could should be an X capital A from the mother,
okay, so that is the genotype of 4. So 1, we cannot say anything more than X capital
A X capital A, X capital A X small A, it could be one of the 2 types whereas 4 be, can be
or is X capital A X small A, okay, those (are) that is the answer to that question.
Now what is the probability that 14 is affected? 14 is here, therefore we need to look at the
parents here, this is a female, the mother is a female therefore its XX and the mother
is not affected therefore either both capitals homozygous or capital small heterozygous in
both cases the person will not be affected. The father is affected and therefore it has
to be X small a Y and therefore the probability that this male will be affected X what Y,
the Y is coming from the father and what is their probability that this would be a X small
a, that is what we are asking. The probability that this will be an X small
a depends on the probability that the mother is a carrier, okay? Therefore it is something
like this; probability that the mother is a carrier times the probability that X a goes
to 14 or this has become X a, the person as has inherited the Xa from the mother, okay?
The probability that 9 is a carrier, see for example, if the mother is not a carrier then
the mother is XAXA, right, X capital A X capital A, then 14 will not be affected at all, okay
because Y comes from the father this Xa does not matter. So the Y will be affected only
if the affected allele comes from the mother, this X small A. So it is the probability that
9 is a carrier and Xa goes to 14. Probability that 9 is a carrier is half, okay
these are the 2 possibilities and one of which is we are considering and the probability
of X small a going to 14 when X capital A is also there, is another half and therefore
the (probab) the probability that 14 will be affected, 14 will have genotype X small
A Y is half into half, that is one fourth. So that is the answer to the question. I am
sure many of you have the right answer, you can check this.
Let us finish up with what we said earlier. The Mendelian principles as we know (ha) have
limitations. We cannot apply it blindly to everything but we can apply it to large number
of diseases that show Mendelian inheritance, okay? That was the use of learning Mendelian
principles. There are a lot of non-Mendelian inheritances, please check out the video that
is given here. The first non-Mendelian principle that we are going to look at is that dominance
is not always, excuse me, absolute, a spectrum exists. It is not either purple flowers or
white flowers, okay? There is something in between also that could arise. It does not
happen in the pea plant but it happens in many other things.
That is called incomplete dominance or co-dominance is a variant of that and there could be very
low frequency of the dominant allele that we have already seen. This is slightly different
from what we expect. That is the reason why I have put it down as something that is different
from expected. It does not go with the other 2. We have already seen this in the case of
Huntington’s disease, okay? The very low frequency of the dominant allele as long as
you have the dominant allele you are going to get the disease, but the presence of the
dominant allele itself has a very low frequency in the population, okay? So that is what this
means. So this is not always absolute, a spectrum such as this exists from incomplete dominance
or co-dominance to complete dominance.
An example of incomplete dominance (is) is something like this in the case of a different
plant. The, if you take true breeding red and white flowers and cross them together,
the gametes will be capital R and capital W. In the F1 generation, all the flowers would
be pink, somewhere in between red and white, okay? So it is neither red nor white, CR (C)
C capital R, C capital W has resulted in a pink flower, no longer a red flower. And this
is an example of incomplete dominance. You take this further, you have the gametes from
the F1 generation as C capital R, C capital W, half and half and then if you do a Punnett
square analysis, one fourth would be red, half would be pink and one fourth would be
white in the F2 generation. This is an example of incomplete dominance (is) which is different
from that predicted from Mendelian principles.
Very low frequency of the dominant allele, we have already seen the example, one more
example is polydactyly, more than 5 digits in hand or a foot, okay? It occurs in about
1 in 1000 births across the world. It is the dominant allele, one allele being present
is sufficient to exhibit polydactyly, but we know that a majority (is) are not polydactyl,
right? So dominancy dominance does not mean a majority, not always. So that is something
that we need to keep in mind. Similarly achondroplasia, a type of dwarfism,
results from a dominant allele again. In India, about 1 in 15,000 have this achondroplasia,
in the US about 1 in 400 have achondroplasia. And double recessive alleles are most commonly
found in the population because if one allele had been dominant, the achondroplasia would
have settled whereas we know that only 1 in 15,000, are have the disease which means most
in the population do not have rather they have recessive alleles they have (de) they
do not even have one of the dominant alleles. This is the very low frequency of the dominant
allele. We have already seen an example of Huntington’s disease earlier.
The next non-Mendelian aspect is that, multiple alleles can determine a trait. Okay, not just
2, multiple alleles. For example, it is a very good example that of blood groups, we
all know. We know that there are 4 major blood groups, what, A, B, AB and O, right? And of
course Rh positive, Rh negative, we will leave that aside for the time being. We know that
there are A, B, AB and O and this is determined by 3 alleles, okay, 3 alleles, A (cap) capital
A, capital B and nothing at all and written i, with a small i. I capital A, I capital
B and small i, that we name it that way. These determine the blood group as for us.
The A type results, if it is either I capital A I capital A or I capital A small I, okay?
If it is it is a B group, if it is I capital B I capital B or I capital B small I, and
if it is AB, if it is IA IB both capitals and if it is O, when neither A nor B are present
or in other words, small i small i. These are the alleles. In terms of what actually
happens, this A and B refer to carbohydrates on the surface of RBCs, A and B are different
carbohydrates. And I A or an A carbohydrate is represented
by a maroon circle, a B carbohydrate by or a red circle, B carbohydrate by a blue circle
and if there are no carbohydrates neither A nor B and it is small i. So if this is the
red blood cell disc shaped red blood cell, if it has all A carbohydrates being expressed
then it is blood group A. If it is all B carbohydrates being expressed, it is blood group B.
If it is both A and B carbohydrates being expressed, it is AB and if none are present
it is group O, okay? And this is also an example of what is called co-dominance where both
A and B are expressed are shown are showing up simultaneously, okay? That is what is called
co-dominance which is again a difference from the Mendelian inheritance.
Pleiotropy is again Non-Mendelian. This means that the same gene affects many characters,
not just one, it it affects multiple phenotypes. An example is from this the same gene causes
symptoms associated with sickle cell disease as well as cystic fibrosis, okay? You can
look at the video that is given here, the last video that is shown that will give you
some more details about Pleiotropy.
Epistasis, which is the expression of a phenotype due to a gene at a locus, I mean epistasis
arises when the expression of a (phen) phenotype due to a gene at a locus is dependent on another
gene at another locus, okay? Expression of one is dependent (on) on the other. If that
happens then it is called epistasis and again this is clearly non-Mendelian, this happens.
Example is the colour of fur - it could either be black which arises from a dominant B, capital
B or brown from a double recessive small B. But, the colour of fur is determined whether
the colour itself is expressed or not, okay, whether the colour will be deposited in the
fur or not. If it is deposited then again it is dominant, if it is not deposited it
would be recessive, double recessive, homozygous recessive. So the not only what colour it
is, whether the colour will be deposited in the fur, both determine whether the animal
turns out to be black, the animal fur turns out to be black or brown or no colour at all,
white, maybe.
This is an example of such a cross, okay, in other words you could analyse this using
a dihybrid kind of, dihybrid cross situation. If you do a dihybrid between colour and expression
of that colour, okay, whether the (depos) whether the colour is deposited as shown by
this E, then this kind of a Punnett square results from these 2 characters for these
2 aspects, or these 2 characters and both those characters together determine whether
the colour is seen ultimately in the dog or not.
For example in this case, 9 would have the colour, 3 will not have the colour, 9 would
(have) 9 would be black, and 3 would not have the colour at all whereas 4 would be brown;
the dominant, recessive and no colour at all, right? So this is different from the classic
Mendelian Punnett square, for 2 characteristics.
Polygenic inheritance is another variant again from Mendelian inheritance where multiple
genes determine the expression of a character. The skin colour is determined by 3 genes.
The human height is again a good example of polygenic inheritance where multiple genes
determine the height of person. And therefore there is a smooth variation, there is a continuous
variation in heights, in skin colour and so on so forth, because multiple genes are determining
this, in the case of skin colour it is 3 genes.
This is a Punnett square it shows a tri-hybrid cross. As you could see at least 7 different
possibilities exist, no colour at all when everything is recessive here and then 6 by
64 of this colour, 15 by 64 of a slightly darker shade, 20 by 64 of a darker shade,
15 by 64 of a darker shade and this can be obtained if you do, if you go through the
various numbers of the blue, bluely shaded stars that are given here, that would directly
show the intensity of the colour here and as you go along the intensity increases, 15
by 64 for higher intensity, 6 by 64 even higher and 1 by 64 the darkest, the darkest possible
here that arises of all these 6 are of a certain kind, okay? So these are the various phenotypes,
the number of dark skin alleles and so on and so forth where 3 different genes determine
the skin colour.
The last thing that we are going to see is that even the environment could have an impact
on the phenotype, okay? Not just the gene, the environment in which the gene is expressed
could have an impact. For example nutrition affects height. The height could be determined
by a number of genes but whether the person grows up to the height potential, depends
on the nutrition, right? So the environment is determining the height. The exercise affects
the looks, maybe you are born with the looks but you need to exercise to reach the potential
in terms of the looks. Experience helps intelligence and so on.
The pictorial example that I have here is the colour of a hydrangea flower. It could
either be this colour or this colour depending on the acidity level of the soil, okay? Nothing
else, it is a same gene, same expression and so on and so forth but which colour is expressed
determined is determined by its environment and condition, in this case the soil acidity,
okay? I think that is good enough basal information
in terms of whatever we looked at after an introduction, we looked at biomolecules, in
terms of stories and so on, just to make sure, it is just not a set of information. We saw
that there were 4 major biomolecules, carbohydrates, proteins or amino acids, whichever you want
to call it. Then nucleic acids, lipids and each one has their own structure and the structure
determines its function and so on and so forth; that was the major take-home lesson from that
particular set of lectures on biomolecules. And we also looked at cell growth; why is
it important to quantify cell growth; by cell growth we mean the population growth, the
number of cells or the mass of cells increasing, mass of cells per unit volume, number of cells
per unit volume increasing with time, okay? How do you go about quantifying that you can
do that using the first order relationship and how you could use that to find out the
time for operation of a bioreactor, that also we saw?
And then some principles of Mendelian genetics. The Mendelian genetics that we had developed
a long time ago, it was given as a part of (an) of a basic course because although they
were developed a long time ago, they are simple enough to be easily used to predict the occurrence
of certain genetic disorders. After that we saw some variations such as X linked inheritance
of disorders and the non-Mendelian inheritance characteristics, very many different kinds
of those, okay? You could look at this in association with
what you pick up from Dr Madhulika Dixit’s lectures, and that would give you some basis
on the molecular aspects of biology which you could apply to your own requirements later,
to address your own challenges later. At least you have been exposed to this, you know where
to go and pick up more information more specific information as and when the need arises, okay?
One last thing, I would like to leave you with this thought to tell you the level of
complexity that we are dealing with even in (understand) understanding the cell completely.
Once we understand the cell completely then possibly the manipulations aspects can get
more rigourous and we have come to a stage where you could manipulate life. But, to give
you an idea of the complexity that is involved let me just show you this.
I am sure you watched the video from nature publishing which was on the human genome project,
which showed that the information in the DNA is transcribed to the information in the mRNA
which gets translated to the information in the proteins, okay? And that is actually called
the Central Dogma, as you already know by now. And we are so interested in proteins
because they are important molecular workhorses in the cell, they do lot of things in the
cell, each biomolecule is very important and there (this is), there could be more of a
focus on proteins because it does so many things that are very apparent, that the basis
of things that are very apparent, okay?
Let us look at some issues. When the DNA project, DNA sorry, when the human genome project was
initiated the initial thought was, since DNA leads to proteins, if we know the complete
DNA or the genome as it is called, we know the cell, okay? The source is Genomics view
of the cell. If we know the blueprint we know the cell, okay, that was thinking and that
was the motivation behind knowing the entire genome structure of humans which we came to
know about 15 years ago. However we were in for a lot of surprises.
Humans had only 20 to 25 thousand genes, okay, that is from this site 20 to 25 thousand genes
whereas even a pesky mosquito has about 13,683 genes, okay, not, not far apart from humans
as we thought. And not just that rice has 60,000 genes. And there goes the concept of
us being superior, right? This has 3 times the number of, approximately 3 times the number
of genes that we do, okay, 2 and a half to 3 times, okay? So we can say that, if we assume
that we are the most complex I, I am not very sure about that, but if we assume that we
are the most complex we can say that the complexity is not explained by genome size, right?
Then people started thinking, if we know the complete set of m RNA, because DNA information
goes to mRNA information through transcription, so you know the complete mRNA information
which is called the transcriptome which can be done through micro-array analysis and so
on, then we know the cell, and if you know the complete set of proteins, the proteome,
we know the cell. If you know the complete set of metabolic
reactions that the proteins catalyse through and so on so forth, we know the cell because
there are so many interactions that are taking place and so on. And this can go on and on,
okay, the level of interactions between these various kinds, are so many. So when can we
understand the cell really? That is the question, you do not really know.
Also, interactions between individual units, say proteins, amongst proteins itself is 1;
protein-DNA, okay, or protein-something else or maybe carbohydrate-something else and so
on or reactions that (oc) that occur in the cell. And do these units function under energy
minimum conditions - unlikely, right? And are there higher level interactions, ya definitely
there are and how do you go about understanding this.
And as we speak, people are working on all these things. Hopefully sometime in the future
we will have a better understanding of the cell and therefore a better understanding
of life itself. Hope that you enjoyed this course (and) there will be a few more lectures
that come up in terms of, which takes, or which throws light on some of these aspects
such as DNA, the processes related to DNA and so on. Wish you had fun. Bye.