Genetics 2 voice
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Genetics 2 voice

This is Dr.Sargsyan, and this is the second
part of genes and genetic diseases presentation. I would like to talk about
mutations, and that mutation is always a change, and it’s not a welcome change. As
you know, although at some time, mutation may occur, and you will not see any changes
in organism, or in the behavior, or in the appearance, or in a functional changes of
the organism. So dramatic presentation of the mutation you see, in horror movies, is
obviously not the case, many times when mutation occurs in real-life situations.
So, to remember one of the important points here, I would like to say that
mutations can be transmitted to offspring, only in gametes, basically what
I’m trying to say here, when gametes are mutated, or if the
mutation will be transmitted to the offspring, that we have a generation of
transmissions, and the children or offspring will present with the
mutations already that occurred in the parent in somatic cells. The harm can be
done to the parent, however somatic cell mutation will not be transmitted to the
offspring. So, from the generation point of view, it’s important to prevent
mutations in gametes, to in order to produce a healthy new generation.
Point mutations, is one of the type of mutations, that is caused by a single
nucleotide base pair change, in the DNA’s. So, when we’re having a single nucleotide
base pair change in DNA this may have absolutely no consequences, because of
the redundancy of the DNA, because of the repetition in the DNA. So point mutations,
may not really have any consequences, rates of spontaneous mutation may vary,
and they very per gene, and depends on the factors that can also influence the
genes at a given point of time. So mutation, can be described as anything
that alters the genetic materials, chromosome aberrations, or base pair
substitution. This is for all types of mutations. Substitution of the base pair,
may result in the change of amino acid sequence, which means that protein will
not be produced the way it was designed to be produced. So, this can have drastic
consequences, if we are having change in the protein. However again, if you are
having a silent substitution, this may not result in amino acid change, again.
Again, because of the redundancy of the genetic code.
So, when amino acid sequence is changed by a base pair substitution, again
the drastic consequences can occur because, when we’re changing the base
pair, we are changing the amino acid sequence, we are changing the protein
synthesis. Just a couple of words about mutagens-
mutagens are the agents that are known to cause, or increase the frequency of
mutations, agent, influence factor, you can use those words interchangeably, but the
main point is, is something that will cause the DNA to mutate. Radiation is,
very well known and studied in 20th century cause of mutation, also chemicals,
and by chemicals we have a wide variety of chemicals that can cause mutations,
however, some chemicals can be extremely harmful, while others can cause mild or
insignificant mutations. The good example of the chemicals, or agricultural
chemicals pesticides, herbicides and fertilizers, but again, the rate of
mutations related to these chemicals is very low. A good example of relatively
harmless, or a weak mutagen is sodium nitrate and sodium nitrate is very
widely used fertilizer. It doesn’t mean that, you can put your hand in your can
of ‘Miracle Grow’ and spread it with your hands, just always use gloves protection,
wash your hands, and protect yourself from even weak mutagens.Silent mutation-
again as I mentioned, is a DNA sequence change, that doesn’t change the amino
acid sequence of the gene. You know the production of the end protein, it’s what
we care about the way your DNA looks. We really don’t care, but we care about
changes in protein, and with all the consequences that come from it. Missense
mutation, is a type of mutation, that results
in a single amino acid change, in the translated gene product, basically again,
remember that, protein is nothing but polypeptide chain of amino acids, which
are peptides, and if just only one of this amino acids change, then we’ll have
missense mutation, can it be drastic, it can be, because, just changing one amino acid,
may result in significant change in the protein, and call it the missense mutation
or be a consequence of missense mutations, or missense mutation, is a type of mutation
as it says here, that results in a single amino acid change in the protein
sequence. Nonsense mutation- this is a type of mutation, where messenger RNA
stops codon, and the produced protein will have premature termination of the
sequence, or the opposite of that, production of the long protein will
happen. So, this nonsense mutation is also quite disturbing process, because it can
affect the messenger RNA stop codon, and either your protein is too short, or too
long. So the main point here is, your protein, it’s not what we wanted it to be,
so it’s different protein. Again, not a good thing in genetics. Nonsense mutation
is described here in details, and let’s talk about premature termination, type of
nonsense mutation. As you can see here, in the sentence- ‘The fat cat
ate the rat’, so it prematurely terminated, and ‘the fat cat ate’, well! the rat is gone,
and you know, we don’t know what the cat ate, so this is different, you don’t want
the cat eat something else, and I’m saying this, and I’m putting this here, so
you guys would remember. So, this is the sentence turned into a nonsense, to
help you remember, that we had a good sentence. Here it is saying, ‘the fat cat ate
the rat’, and now, ‘the fat cat ate’, what did it eat?, did it go to the pet store and got
the cat food?, who knows. So that’s the nonsense mutation, with premature
termination, another type of nonsense mutation is, when your protein starts
getting longer and longer, and when it has to stop, it doesn’t stop. So, with the
same sentence, ‘The fat cat ate the rat’, so it turns into another sentence, which is
again nonsense, tough ‘a cat ate the rat and the hat and the mat’ so I don’t
know, if your cat eats the hat and the mat, mine doesn’t, but you know, this is
not typical cat behavior, and you can remember that’s the, it’s the nonsense,
the sentences are nonsense, so nonsense mutation is related to messenger RNA, and
the codon is not activated, at the time when it should be. So your sentence, or if
we talk in protein language, your protein is either too short, or too long, but it’s
not just the right size. Frameshift mutation occurs, when DNA is altered, and an addition or deletion of base pair
took place, so shift is not a good thing in here, because the entire frame, reading
frame, so called reading frame is transposed and changed. So frame shift,
let’s say I inserted just one base into DNA molecule, but if you think about it,
everything else beyond that one base changed, and every single codon, every
single base is not correct. What happens, this definitely won’t resolve into
silent mutation, you will see the consequences, because it’s just not,
although we change just one base, we added or deleted, but everything had a
shift, so everything is different, so frame shift mutation can result in the
entire change of the protein appearance, and protein amino acid sequence. So let’s
talk about consequences of mutations, what can happen- either gain of function, or
loss of function. So, something was dormant, and now it comes up to life, or too much protein production, over
expression, under expression, or inappropriate expression. This all can
happen, because again, we are talking about protein production, nothing less or
more. When we are talking about DNA, as you guys know, it’s all what happens. DNA
is read and protein is produced secondary to DNA composition. So all this gain of
function disorders, can be consequences of mutations, and even though
there is a gain of function disorder, they still are not a positive change, it still
can tax the organism very much. Another process that can occur, another
consequence of mutation, is loss of function, and its associated with
recessive disorders. So, at this time, you will lose 50% of protein product, and I
won’t be telling you why, I want you to think about it, and just ,this is an
important point, but it’s very easy to find. If you don’t find the answer, please
let me know, and I’ll help you, email me or call me. So, on the other hand, this is
not that bad, even if you lose 50% of the protein
product, it may or may not be adequate for normal function you know, and there
are functions in the body, that you really don’t need hundred percent of the
ability to function adequately. So, but again, I would like for you to look
through this, and tell me why this is related to recessive disorders, and why
most importantly, loss of 50 percent of protein product occurs, not 51 or 42 ,but
50. Chromosomal abnormalities can be quite widespread, and the most common
chromosomal abnormality presentation is early miscarriage. In early miscarriage,
most of the early miscarriages, they occur secondary to chromosomal
abnormalities, and sometimes, even this is not detected
as a pregnancy, it is so early in the gestation period, but to talk more about
this, we need to emphasize the concept of euploid cells. Euploid, or you know you
euthyroid, (again ‘eu’ prefix in Greek means normal or true, correct-
different interpretations, but basically the normal cells have a stable , correct
number of chromosomes, that’s what we mean by euploid cells, and we when we’re
saying haploid and diploid cells, they still are diploid cells, they still are normal.
So haploid, have the half number of chromosomes, so the gamete are the sex
cells or the sperm and egg cells, and they are haploid, at the same time, they are
euploid, and they have 23 unpaired chromosomes, and I’m sure you all know
that, but I have to repeat it, just to review the material, diploid cells have
paired chromosomes, and human cells have 46 chromosomes or 23 pairs.Again, diploid
cells are euploid, formed as well. So, in changes, when euploid cell has more than
double number, it is called polyploid cells. So triploid cells, when the zygote is having
three copies of each chromosome, and 23 times 3, is 69. Tetraploid, when there are
4 copies of each chromosome, it’s 92, just common, common knowledge in genetics.
Triploid and Tetraploid fetuses don’t survive, there is no way, this type of
foetus with triple or quadruple number of chromosomes, will survive. When we
talk about, lack of normal number of chromosomes, we are talking about
aneuploid cells, and by saying, lack of normal number, I mean this is a contrast
to euploid. So, euploid cells is the multiple of normal 23 chromosomes. So, euploid, still can be tetraploid, which is abnormal, and has no chances to survive,
but still it’s euploid. Aneuploid, means, there are not just 23 chromosomes
multiples, you cannot divide the number of chromosome by 23. Monosomy
is, when there is only one copy of any chromosome, right? Again, remember the
concept of parent pairing, the pair should be there, for the chromosomes to
function normally in somatic cells, of course.
So, monosomy is, when there is only one copy of the chromosome, basically the
other pair, the other member of the pair is missing. Monosomy
is quite commonly fatal, so if there is a chromosome missing from the pair,
but if there is extra copy of the chromosome, the infant may survive and
lead a relatively normal life, and but, it’s usually the excess chromosome. One
example is, well known example is, trisomy 21 (Down syndrome) and we know nowadays,
that people with Down syndrome, may develop mentally and physically, they can
progress in their development, and some of them, even go to college, and have
happy lives, and but to emphasize this notion again,
it’s better to have more than less, or it’s better to have extra than less. If
there is extra genetic material, chances of survival increase with genetic
abnormality, if there is missing genetic material, chances of survival decrease,
and to explain that, you basically don’t have enough blueprints, to build whatever
you are building, if you have too many blueprints, it may be confusing, but you
still may be able to build your building. When we talk about chromosomal
abnormalities, we are talking about also nondisjunction, and disjunction
as you know, normal separation, when chromosomes separate during the cell
divisions, they go through disjunction. Nondisjunction is non division,
non separation, and usually, it will cause aneuploid cells, aneuploid number.
So basically, part of the pair, or the pair
had either disappeared, the member of the pair disappeared, or it went to a
different place, where it’s not supposed to be. So, it may cause trisomy or
monosomy. So, this is the concept of nondisjunction. If the homologous chromosomes, are failing to separate normally, during the division,
either meiosis or mitosis that can lead to nondisjunction. Again, nondisjunction
concept is, when your genetic material as chromosome moves to an unusual place and
causing monosomy, trisomy. Basically, we don’t have euploid cells anymore, we have
aneuploid, We don’t have multiple of this 23 number, magic number of 23.

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