Okay you all so as we get started there is
a group of core vocabulary here on the left hand column that you do and you do need in your
notes. So this is an applied bit of information, but the good thing about all these terms is that
these are phenotypes that occur sometimes because of accidents or injuries, sometimes because
of a genetic disorder, sometimes because of other kind of mix of conditions. So these terms
here from Ataxia down to Strabismus are things that you'll see as a accumula
tion of phenotypes
that result from having certain kinds of genetic conditions in the examples that we're going to
talk about. But one of them alone is not a sign of any one particular outcome. So please here:
ataxia. Ataxia is the first one. Cryptorchid. Third one Dysplasia or dysplastic. Fourth one Gynecomastia Five Hypertelorism. Hyper as I'm
sure you're already familiar with, is going to mean when we're looking at
something that is too much, too strong, or above. It means more than in s
ome value.
Hypotonia. Hypo, not enough, not a strong enough, less than, or below. Like a hypodermic needle
goes below the surface of your skin. So hypotonia. Microcephaly. Microcephaly. Micro means not
enough, so very, very small, not the standard. Simian crease. And then the last term
here for us in this lesson Strabismus. We'll do these right now so that we don't have to
linger on the slides when we get to the examples for that. So in your reading be sure that you take
a look for, and sl
ow down big time, when you see any place that's talking about mutation. And
then we'll have it also in this presentation today. Mutations are first produced or introduced
for you at the end of 3 when they start talking about things that happen during cell division.
So you've got some of that on page 50 and also on page 48 then you have a big
breakout section on mutations on page 68. and along in chapter four and then it's a huge
part of the conversation in five can't overstate the importanc
e of thinking about mutations
because we're really heading towards being able to understand describe and have the terms
for how populations become genetically diverse so as I put it in the chat because natural selection
only works when you have variable characteristics in your species population. Sources of mutation
again, quite a number of them are really called out in your reading, I jotted a couple of ideas
and we'll have a couple here in this presentation. And then levels of mutation.
So today we're also
going to take a look at the difference and the definition of a point mutation. With an example
of a well-known genetic disorder, or condition, that's caused by a point mutation. Abnormal chromosome
structure. We're going to look at three examples of abnormal chromosome structure and see what the
outcome of that tends to be. And then the third one abnormal chromosome number. When something
much more major goes on, and an individual has more chromosomes than is norma
l for their species,
or not enough chromosomes for their species. Usually abnormal chromosome number in
humans is not survivable and would result in miscarriage, but sometimes, it depends on
the chromosome, sometimes the individual has normal longevity, a human appreciation
and fulfillment of their lifespan, and so forth. It really just depends on too,
many too little, and what chromosome, and whether it's an autosome, or whether
it's a sex chromosome. Okay so here we go. Mutations. Whe
never any cell divides, mutations
may occur and that's just because as the chromosome copies itself and then lines up with
its copy in the x form, which are the chromatids attached to the centromere, if all that doesn't
go smoothly then even for somatic cells there can be changes. However, this is the big
one for our class: if we're looking at cell division that produces a gamete then
mutations always occur. And this isn't an exaggeration or me being emphatic. We know
that all gametes ca
rry mutated chromosomes. So meiosis is one of two types of cell division
and that's the type that produces a gamete so you've got a couple pages of reading and diagrams
in three there is an entire page in canvas devoted to the video on meiosis and also asks you to
jot down the statistics of how many different combinations of chromosomes you can produce
within one person or with another individual so they always occur so meiosis always produces
a mutated chromosome so you and i and every oth
er individual organism on the planet that's
the product of sexual reproduction and that just means there's a gamete and it has to meet up with
another gamete and that includes the majority of plants for instance fishes humans insects etc we
are all slightly mutated versions of our parents so diversity and variety is always
being introduced to our populations but for us in class reproduction who's reproducing
reproducing with whom how frequent is it what is being selected for and perhaps not
selected for it that is the big concept for the balance of the course and that's because mutations
that occur in gametes play a role in evolution mutations that happen in your somatic cells
do not play a rowell and rebel in evolution and that's because your code was set when you
were created as a fertilized ovum and then that code stays the same for the rest of your life
if you get a mutation in a somatic cell say for instance because you've had too much of a certain
type of radiation you
end up with a condition we call cancer those cells stay in you you can't
pass them to the future since they don't go to the future they don't play a role in evolution so
really it's just what's going on with the gametes that we send forward and that's why also when
we were studying this we were only looking at the concept of fitness being related to
who actually does reproduce not who could or who had an offspring but that didn't
survive very very long but who actually passes their genetic
combination to the future
to a grandchild generation so gametes pass to the future so anything that's changed in there goes
into the new population gene pool so they persist you might have heard people say some version of
this in many different languages that children are a form of immortality and that is correct it
is the organic part of you that can keep going the thing about mutations though is in
the dna molecule along the length of the chromosome there's no place where it's more
or l
ess likely to occur. So it's really random and unpredictable at least as far as data that
we have right now to figure out where it might occur and what the outcome might be. The ones
that matter the most though to evolution are certainly going to be those that are in the
exons with structural or regulatory functions because those are going to make the difference
between whether the offspring is going to be able to function just fine and become a parent
and reproduce. or perhaps not live l
ong. or live fine but not be a parent. And
occasionally when you're reading about this a little bit more you'll see the
phrase germline. Germline means we are tracking these cells that go to the
future. So that's what germline is. all right the result of mutations one of the
interesting things about thinking about mutation for the understanding of it in the entire
general population is that the general public knows what the word is and knows that sometimes things can really go wrong in fa
ct actually
the majority of people when you say mutation think that that means that all the time things
really go wrong when you have a mutation if you look at this just socially for those that you have
other majors like in media or in literature or in things that might be more popularized for the
public probably the public's awareness of this comes from mid-century in the 1900s and is mainly
associated with the invention of atomic weapons not very much information was passed to the
public
but all of it was incredibly scary they knew that they were incredibly
destructive but they also knew that as the after effect of the use of them against the
japanese public is that not only did it destroy buildings but even for some of the people that
survived within a short period of time they had massive genetic changes that were causing them
to pass away in horrible conditions particularly cancers and then of the next generation for those
that didn't pass it's it was also still buildin
g up that this mutated genetic combinations were
causing cancers and other conditions to be more pronounced in the population so it was scary it
was ugly it was evil it was mean it became a very very frightening thing once the technology was out
then it became something that even for kids during that particular mid-series uh century period of
time that instead of having that like horribly scary drills that we have now in public and some
private institutions for little kids the active shoote
r drills where the kids are just frightened
to death and they're getting ready for something out of their control to happen the same thing was
happening but with a different type of drill and they were having bomb drills atomic weapon drills
big mushroom cloud things and even though nothing that the kids did or the school would have done
would have saved their lives because this was this unstoppable force they would be hiding underneath
the desk covering up and and just be terrified that te
rror flowed over into creativity and we see
that it's about that time where we start to see more of these post-apocalyptic visions
in literature or movies. The sci-fi movies, horror movies, zombies are taken as a concept
from a real indigenous activity and concept , to something that's related to weaponry
and warfare and other kinds of awful nasty things that humans do to each other. So
everybody got some awareness of it, but only when the mutation was deleterious. Here so deleterious
is your college student vocabulary word for having a bad outcome. In terms of our course a deleterious
mutation is really going to be something that makes it impossible, or harder, or not as successful
for that individual organism of their species to produce offspring. So think of it this way:
when we're for our course when we're looking at evolution. A mutation that makes it so that maybe
a portion of your physicality isn't formed exactly the way that it's standard, or maybe doesn't work
quite as easily, if it still allows you to survive, be reasonably healthy, and live long enough
to reproduce, and parent effectively, it isn't actually, in terms of natural selection, that
deleterious. So a human, for instance, that's born with extra fingers, or missing fingers, or a human
that can't hear for instance, because we're a social species and our community fills in the
blanks for that, that really wouldn't be a minus to your ability to reproduce. So a deleterious
mutation, pe
rhaps you're not making any sperms, perhaps you can't digest your food, perhaps there's
something else going on so that no one would like to be your reproductive partner. Or they don't
choose to do that. So deleterious mutation so that means bad for continuing
your line, Next one: Neutral mutations. A Neutral mutation is actually probably the most
common outcome of all genetic mutations for any species. And that means that whatever the
code that was changed isn't making any difference in t
he proteins that you need, or that you're
producing that help you to stay alive , and live, and function. So if it doesn't have any effect
on reproduction at all, and and the individual lives long enough through their reproductive
max time, then it's neutral. We do know that this is probably likely statistically to be the
most common outcome of most types of mutations. We just notice it when it's the other ones. It
also is true that mutations can be beneficial. so there are kind of a lot
of examples of that
if you wanted to look into it into one more detail but I'll give you a quick example before
we move on. Beginning in about the 1980s and getting closer to 1990, there was a lot of global
research on the human immunodeficiency virus. It wasn't a new on the planet, it was already
present in other species, but when it finally got into humans it caused major disruption in
human lives. It didn't really actually cause major disruption in other particular organisms which
is
something we'll look at later on in the course . so while they were looking for this they were
trying to figure out most specifically method of transmission and how dangerous it might be
to have a co-worker or a parent or a neighbor or something else because it was a virus and they had
to figure out how viruses were passed when they started to look specifically within households
of people who were actively exhibiting hiv to their sexual partners who were with them and
were having intimate
contact they found in a few small places one of the populations was in a very
small region in italy where there were quite a number of individuals in this small town region
that had been exposed over and over and over again because their long-term partner or spouse
was positive and they never caught the disease and they found out that every one of them had a
oddball mutation that made it so that the human immunodeficiency virus couldn't get into the right
cells and so they were immune that'
s a beneficial mutation at the time that that disease
emerges so mutations can be beneficial thinking about neutral mutations though because
this helps us to review something that we looked at today and also on monday because about 74 75
of your base pair sequence is non-coding if there is a mutation within that region and it doesn't
turn anything on then the outcome is neutral like nothing has changed it hasn't made any active code
that's making a structural change or a regulatory change s
o if uh mutation is not changing your
phenotype practicing some more vocabulary here then it is neutral mutations in non-coding regions
or if they don't change the amino acid sequence if you remember from last time when you look
in Chapter 3 at the amino acid table, some of those amino acids can be celled spelled
six different ways. So if the base pair sequence makes a small change but it still makes the
same amino when you're getting the same protein and everything stays the same. so that'
s
what a neutral mutation would be like i have a question yes go ahead um go ahead um so so like a neutral
mutation just is just talking about whether it affects your phenotype and how
it goes right right so would that mean that let's say coronavirus uh itself since it's a
mutation and that means the neutron mutation um so so coronavirus itself yeah is something that
has a mutation from something that was already present and that mutation for coronavirus has made
it very easy for people to
catch so for actually whatever that mutation was for that species
right because viruses are their own living things they're their own genus and species so that
was kind of a plus for the coronavirus to make the change that it is because when it makes us cough
and sneeze and because we carry it for a while before anybody will know that you're sick so that
was good for that species it hasn't been good for us so we so far haven't seen where that's going to
end up for that but yeah every organ
ism gets its own mutations is that kind of what you were asking
towards actually i was just wondering if like what corn advice we consider a neutral mutation
or like uh is there a good or is it a bad one for humans it is um an agent of natural selection
right now and it is thinning out some segments of our population. So it is a natural thing. It's
not happy but is a natural thing that happens in nature, particularly when any species becomes
extremely overpopulated and really crowded. Ri
ght ? Which is why we saw it tear through big urban
environments first, and where we see that some places in the world or even states in the United
States where there aren't very many big cities, and people live really, really separated. Where they're
really not having very much transition for that . So um coronavirus as a mutation's probably not
quite the thing to think about with it, but it is an agent of natural selection. And at first
they were telling us all remember back in March 2
0 that young people didn't need to worry about this
at all. It was just really we were trying to close down and separate to protect our loved seniors
and older people. Or people that might have some other health issues in our population. But it turns
out it is impacting certain members of our younger population. And it looks like it might
have some neurological or actually even um vein, blood transfer kind of thing. So yeah it has
a natural place in nature. Once it's done making it cy
cle in the future there probably will be
less of us that have the strongest effect of it, other than people that already have some health
issues, but one of the health issues that they aren't really saying about it is obesity. So
people whose respiratory and heart system is already under a lot of pressure. Because they have
a lot of body mass or having difficulty if that yeah. So not this not the best way, but nature does
bring populations down in every species when they become overpopula
ted. And so since we don't manage
it, and space ourselves out, and manage our birth rate around the world then nature will do
it. It's the same thing that happens with rats, and weeds, and other kinds of stuff. So there's
happier ways we can manage this. Okay so, so fitness again. Really practicing for this unit
and all the rest of them. Fitness is whether you're going to pass along your characteristics
to the future to a new generation. So it can affect anatomy or physiology but n
ot have any strong
role as to whether you're going to reproduce. So for instance if you have a mutation that
doesn't make you really falling apart, or really sick, or really not able to function until you're
30. Well you still had between about 15 to 30 to become a biological parent, so that really isn't
inhibiting your opportunity to pass your genetic combination to the future. So that's kind of the
idea of neutral here. All right so we're going to look at now, we're switching over, if
you go to
a new page or go down a few lines, we're going to look at point mutation and then chromosome
structural mutations before we um are wrapping it up for today. So the we're on this one, just
this one that's brighter and white, point mutation. We're going to look as an example of a point
mutation - at sickle cell disease or sickle cell um condition. Sometimes called sickle cell anemia,
and this depends on kind of who you're talking to, and whether it's really medical, or how
the co
nversation is. There are lots of other examples of point mutations but this one is
been reasonably common in the global population for as long as we've been looking at these
kinds of disorders. So we're going to define what a mutation is, and then take a look at
how these can pass along. So point mutation okay now contrary to what a lot of people in even urban
american society think sickle cell disease is not something you catch
from another person it is something that can be inherited
so it can be passed from
a parent to children but here's the third part anyone with this mutated gene has the disease
so you can either get it as a mutation and it will be present then from when the
baby's born or it might be inherited it is not only a portion of the african population or the
black american population it is a fairly common genetic condition in africa south and central
america caribbean islands india saudi arabia and right in that warmer part of the
mediterranean turkey gre
ece and italy basically this particular mutation affects just
one thing in your body and that is the ability of your red blood cells to withstand pressures
that happen when you have low oxygen density so this little girl here tiana hughes was one
of the us child ambassadors isn't the current one but was before now as you can see she doesn't
have any really horrific things going on with her at the moment we have very good treatments
for this nowadays we've got if you've got insurance or you
have access to blood transfusion
and some other types of treatments they can really make a big difference and not everyone who has a
copy of the gene even actually knows that they're carrying a copy of the gene because their symptoms
can be fairly mild so under the microscope what happens with this mutation is it causes red
blood cells which here should look like this all the time no matter what even if you're exercising
even if you're sick even if you're exhausted to look sort of like a li
ttle breath mint that
has a little dent in the middle or a pillow when you have one copy of the sickle cell
gene then what happens is under certain stressful physical situations
this warps and takes on this sickle or crescent shape when it does
this it can't do its job as well or at all so we're going to investigate this a
little bit a little bit more detail here okay so basic definition of point mutations and
it helps us to practice some terms we've been working on for about a week so a p
oint mutation
occurs when one base in the cell changes so only one nucleotide has a change you got three
billion bases in your system so there's three billion spots where point mutations can occur
but we don't know about it if there's a change unless it's in a place that's got active
code and then that code is altered so sickle cell disease is caused by a
point mutation just one nucleotide changes and in that particular case the code for your
polypeptide chain remember polypeptides that's
the chain of amino acids the triplets turn into
codons and they make the amino acids is altered and it's got to be in the sequence that
makes hemoglobin which is another form of protein and we call that red blood cells if
an individual has only one copy of the gene they don't have two copies right they have
it they don't have both alleles the same but they just have one of the alleles then they
will have much milder symptoms to level that it's possible in many cases that they never
actuall
y find out that they even carry this gene however if you have two copies of it you will
know it the child will know it right away it'll be very very obvious and they will need
assistance treatment and mitigation so as an example of when you have just one copy of
the gene right when you're heterozygous for this mutated gene my example person here is
even if you have never heard of this man you know from his outfit
and his general physicality that he's insanely fit he was a professional
foot
ball player in the nfl for quite some time the giant steelers and redskins this
is ryan clark he was a starter and we all know how often you get injured how
exhausting it is how much exercise and time you have to spend in physical training
we know that to be able to play like this in the nfl you started when you were much
younger yet he actually never had any type of noticeable event until he played a game at the
high altitude at the mile high stadium in denver at that particular point in h
is life as
a big super healthy super energetic human he actually had an attack and had to go
to the hospital what happened was that the oxygen deprivation that was happening because
at altitude there isn't as much oxygen as the air was stressing out his blood and it was stressing
out everyone else's too but because he had one copy of the gene a portion of his red blood cells
sickled and that caused something that's known as an infarction infarction is a really scary term if
you hear this a
t the hospital or you know someone that's had this as a diagnosis because infarction
means that your blood supply has been obstructed so when those sit those cells warped then
they caught on each other and they blocked oxygenated blood from coming in and out of
his spleen so he did recover it didn't end his career i think he's currently now coaching
and doing some other things and as the awesome person that he is he is a founder of ryan clark's
cure league last time i looked into this they
help with funding not for research or um not
from the sciency part but actually funding for families who need financial assistance because
they don't have insurance or they might not have transportation or they just need help finding help
um finding doctors and finding treatments and then paying for it so yeah so there are other celebrity
uh individuals that i could have picked but it's really easy we all know how often and how physical
that particular career so one copy of it is not someth
ing that's gonna end every part of
your life two copies much much more dangerous now hopefully this is gonna run for us just
fine you should be able to hear this this is only a minute it's going to talk about
what happens and why it's called sickle cell sickle cell anemia is a genetic
disease that affects hemoglobin the oxygen transport molecule in the blood the disease gets its name from the shape of
the red blood cells under low oxygen conditions some red blood cells become sickle
shaped
and these elongated cells get stuck in small blood vessels so that parts
of the body don't get the oxygen they need so here's your dna sickle cell anemia is
caused by a single letter change in the dna this in turn alters one of the amino
acids in the hemoglobin protein valine sits in a position
where glutamic acid should be the valine makes the hemoglobin molecules
stick together when oxygen tension is low forming long fibers that distort the shape of
the red blood cells and this brings o
n an attack so very frequently you'll see photos of
people who have two copies of the gene of the affected gene with really inflamed joints
and that's because the blood vessels are very narrow and small there and then everything
backs up and when they aren't getting oxygen then tissues are dying so you've got some really
awful things going on for people who have two copies of it okay so to practice again i'm not
going to ask you specifically what chromosome it is but just in case you know s
omeone or someone
in your family or you've come in contact with it this is one base on chromosome 11. and on that
one right a point mutation occurred the t that's supposed to be there was substituted out for an a
and in that case it is not making the right amino acid there and when that is like that then when it
builds and produces the red blood cell then they can't flow constantly the way they're supposed to
so again a couple more vocabulary terms so here if all if you have two copies of t
he standard gene
that's going to make the t here and all your blood cells stay normal and round and don't clog and do
carry oxygen if you are heterozygous and you have one of each then under certain kinds of intense
stress you might have an attack but still most of your blood is carrying oxygen the way that
it's supposed to but if a person is homozygous for the non-standard allele the a allele here
then under any kind of stress all of the blood cells sickle they're not carrying oxygen the
way that they're supposed to it's extremely pain swelling because tissues are dying and it's really
really dangerous condition so you can inherit it or you can be born with the mutation that just
happened and not have it come from either parent if the parents are like this though both of them
could carry the gene and perhaps not know that they're really affected and then pass it along
to the offspring perhaps okay so here it is one last time so here it is point mutation contains
just one ba
se in your base pair sequence but that base is part of the triplet code that makes up
one of the proteins that makes red blood cells all right so you don't need glutamic acid
or valene here just the basics you have one copy or two copies it's a point mutation
and that means it changed one base in the code all right so a couple more terms
here practice a little bit and then also um because you might read about this if you are
going into something that's healthcare related like even the busin
ess of running healthcare or
billing of healthcare or nursing or doctoring or laboratory work analyzing genetic samples blood
samples all that good stuff autosomal recessive diseases there are a lot of them that have been
recorded so first word here from monday autosome autosome just tells you where it's somewhere in
the one through 22 chromosome pairs right your autosums are number one through 22. those are the
ones responsible for the structure and function of you or any other organism to
be able to stay alive
if the next term says recessive then it means that the allele is not all that powerful and so
you will not show the disease or the outcome unless you have two copies so all recessive
situations require that you have two copies and two copies means you are homozygous the
recessive so here's something to put in your notes a little star a little highlight recessive
doesn't mean less healthy it doesn't mean less desirable it doesn't mean that it isn't completely
standard
for the species recessive just means that it's not making an exceptionally powerful protein
and that there might be a variant that is more able to express itself if there is a variant
that's able to mask the weaker one then we say the variant is dominant so recessive doesn't
equal healthy or unhealthy and neither does the term dominant dominant doesn't mean that it's a
healthy variant or an unhealthy variant it just means that if you have one copy of it you know
it you know you carry it it
's going to show up now with recessive disorders they tend to
the genes that cause them they tend to hide in the population and pop up and down over time
there's another one it doesn't cause the same effects as sickle cell but it is inherited in a
similar way and it's the same kind of situation if you have one copy of the sickle of the tay
sachs so tay sachs disease if you have one copy of the tay sachs gene then you don't know it
nothing's really changed but if both parents carry one copy
of that recessive tay sachs and the baby
is born with it then the baby is immediately from birth very very ill and has a very very short
lifespan so it's really sad and really really difficult for the parents and the family because
they are going to lose their baby fairly quickly if they have one copy then the parent is a
carrier and that's what the word carrier is you have a recessive that might be a problem
but if you only have one copy it isn't interfering with your health particularly s
o
you might pass it on even so if both parents are carriers right so they have one of the
standard and one that's not so desirable one of standard one that's not
desirable in each pregnancy it's only a 25 chance that the baby born in
that pregnancy will actually be homozygous for the problem alleles so they only have a one
in four chance of having a baby that's affected last one down here dominant
disorder a dominant disorder is always noticeable always able to see the outcome
or detect t
hat something is different because it means that if you have one copy of a dominant
gene it's going to show up you're going to know like when we looked at blood before we went to
break if you have an a or a b then it's going to show up in your blood type so dominant
disorders are always very clearly present in the family line that somebody's got it
and they might be able to pass it along recessive genes hide and sometimes it's just not
clear whether anyone is affected or carrying that okay
now go down a couple lines let's look at
chromosome structural abnormalities and if we have time we can take a look at numeral
abnormalities so we'll do structural changes first and then numeral second chromosomal
structural abnormalities mean that a whole bunch of the base pair sequence has been changed it's
not just one base or one nucleotide it's multiples and there are four ways that
this generally can occur the outcome of a structural abnormality depends on which chromosome is affected
and what that chromosome does and also how much of its base
pair sequence was changed in numeral abnormalities it means that the
hugest effect has occurred that the individual has gotten an extra chromosome
or is missing a chromosome the outcome of numeral abnormality is profound but
the outcome depends on which chromosome is extra or which chromosome is missing when
we looked at karyotypes on monday one of the karyotypes that i showed you right off
the bat had a red circle around some c
hromosomes and in that circle was enclosing three chromosomes
at that position so that's a numeral abnormality so people with these do have a strong
effect if it's structural or if it's numeral okay so let's look at structural changes so there's four ways that the structure
of a chromosome can be altered in larger sequence and lucky for all people
looking at it who don't do this all the time for a living or for your major what the term says is
exactly what happens so you just have to envisi
on the whole chromosome right with its sugar phosphates on the side and the base is
coming in towards the center and then if it's a chromosome structural abnormality because
of deletion it means that the chromosome broke horizontally between the sugar phosphate and a
chunk of it came out it just is missing let me see if i can do a it isn't that easy but
i think i can do this kind of simply here so here's your chromosome one side and
that's the sugar phosphate side and here's the other sugar
phosphate
side when we're looking at these right you have the nucleotides with
their bases coming in to the center and so forth so as they're doing this
right the dna base that's here has its specific partner if this is a t then
this one's an a if this is a g a c this is a c this is a g and we were
talking about last time that the sugar and phosphate bonds oh boy it's hard to do this
with a well let me use my pen here with the sugar phosphates here these are very strong bonds
these down
the center those hydrogen bonds between the dna bases are weaker and they're supposed to
open up but if this breaks this way and this way right you get a gap in between the sugar
phosphate and the sugar phosphate down here the problem is that sugar phosphate will bond
to any other sugar phosphate it's not picky so if this breaks here and here and it
floats away then the part that's left up here is just going to re-click down here and you have
deletion sometimes what happens is it breaks or
something there's a gap and it goes through a
repairing kind of process and it just adds more sugar phosphate sugar phosphate sugar phosphate
that's duplication duplication is when it adds more code here than was there originally before
the chromosome broke but again the breaking is kind of from the diagrams we've been using in the
horizontal between the sugar phosphate inversion is an interesting one to think about and they have
actually been able to find that with inversion it breaks here
and here but remember the cytoplasm
is liquid and it's three-dimensional it's too tiny for us to take a photo of up close right now
but it is three-dimensional space sort of like something floating in let's say an organized fish
tank so this comes out and it flips upside down so that if this started off as an
a up here now the a is down here so that's inversion it glues it back
in but it's not in the right sequence so that's inversion and
translocation sometimes this breaks and then just
swims off to someplace else
and glues someplace completely unrelated there are examples of it breaking and
gluing onto another chromosome where it doesn't belong what's the end result
though the generic end result for us to think about right now at this particular part in
our lesson the end result is let me see if i can get some of these to go away go away go
away okay and um let's make this one go this one the end result for this is
that when rna comes in to the nucleus to read the dna mo
lecule the dna molecule unzips
a little bit like right down the center here and then rna comes up and reads
a portion of the sequence if some code is gone rna goes to the address but now
what it's looking for at that address is changed it copies edits and carries it out it's making
the wrong thing if it's duplicated same problem all the addresses are wrong in the direction
that it's trying to read if it's inverted the spelling of the word that it's trying to
make is upside down doesn't wor
k and if it's missing and it's not even on here at all then it
never even sees it so all of this disrupt the code that rna reads and makes it so that it cannot
assemble the proteins that it needs to assemble all right so we are just going to look at deletion
mutations so we're going to look at and use some of those terms you jotted down in the beginning
ataxia down to um semi-increase and so forth in terms of deletion mutations i'm going to give
you three examples we're going to look at thr
ee examples and you'll be able to really see um
how depending on what's lost in what way and on what chromosome how you get really different
outcome for the people that are carrying this genetic combination so deletion again when more
than a single base pair is deleted of course the more that's missing the bigger the outcome
um will be in the phenotype so first example please do write down deletion disorder and the
name of this one cree deschat it means cats cry in french i probably didn't
pronounce that even close
to correctly because i never took a french class this is very rare it occurs in maybe a
little bit more frequently than about one in fifty thousand live births when the
babies are born alive and there are kids what is the locus so in this one and here's
a karyotype over here again practicing the concept here's a karyotype so a baby's born
and has a couple of unusual things going on and so there might be some idea that perhaps
this is genetic not a bacterial infect
ion or something going on with the mother's
milk or something else like that so they go ahead and do the karyotype and what
they'll see is over here right autosomes have numbers one through twenty two so they're looking
in the autosomes and then here you can see on this one here's the centromere you all i'm practicing
as many vocabulary words as i can with you centromere right here the little pinched waist so
on the p arm short arm the p arm of the centromere you can see on one of these chr
omosomes this dark
banded area so there's a light one and then dark and then the rounded tip on this one it's gone it
has been deleted so if we look at this even closer you can see that there's a chunk up here that's
missing or in a diagram it's missing up here so creature shot so missing bit of
chromosomes on the short arm of chromosome 5. so the outcome is going to depend on what
that sequence of code is supposed to do on chromosome 5 and the second part on
how much broke off how much is
missing so okay this is um self-posted by the family and
there's an uh narration really going you're just going to be able to see this little um adorable
baby you can see right away that he does have a um a change in the code his coding got
confused and it did not fuse the skin here all the way across the upper lip so
that is a form of dysplasia we might have some popular names for that lip splitting
that's not by itself particularly super rare but dysplasia it just means
tissue that didn
't form in the standard way but let's look at some of
the other things going on with this little one so that's the baby's voice as he's growing up get some
surgery to correct his upper lip and he's getting a little
bit of corrective surgery and then a little bit earlier later on like
regular kids wanting his earbuds and his toys um that was posted by the family um so i
would never take something from somebody that yikes okay so i don't know why that went backwards
all right so again this i
s called creedy shot and obviously this would be one recognizable from a
long time ago because generally that's not what babies voices sound like when they are first born
so first use of the vocabulary words then that you jotted down hypotonia hypotonia these little ones
are born with low muscle strength or muscle um weight or tone that's a better one muscle tone
and so they're very weak so part of the reason is voice sounded so high pitched like a kitten cry
instead of a human baby belting
it out is because they're very weak that can happen when the
mom's not well it could happen from bacteria virus it could happen for other kinds of stress or
injuries it isn't by itself only associated with this or even with a genetic disorder but it is the
first clue right the first little bit of empirical data they need to look more closely into this
baby's health also these children are frequently somewhat microcephalic micro a little
bit smaller ceph is your brain box so the back of the
head that enhouses the brain
is smaller than generally what they see in babies at that birth weight it doesn't also that can
happen from a lot of other different circumstances um and again it's going to vary it doesn't
mean that the brain is missing it just means that it's not fully the size they normally
see so they're also generally microcephalic they do have some very distinctive facial features
and if you just take a look at this little girl's um cute face here i will see another in a
couple minutes or in a couple slides and take a look at that one so the dysplasia that we
saw on the little boy's upper lip where the skin didn't get the right code to fuse straight across
um also can result in some other confusion about building tissue elsewhere sometimes the ears are
not set perfectly and they're very low along the side or here we can see a little skin tag here
just a little overgrowth of tissue in a place that it's not supposed to be these several things
coming together
are would be starting to show the helper medical personnel of what to
be looking for in terms of a diagnosis in this little one this is a different baby than
we just saw the ears are a little bit low set and you can see here that while the baby does have a
lower jaw it's not quite the length it should be to match the full length of the upper jaw that
later on in life is correctable as well but it does mean there's an error in code so can
you see easily from just these few pictures that whe
n it's multiple genes that are
affected right they have one normal copy of the gene but it can't work with its
allele then you start to have a cluster of phenotypes that are affected structures or
functions that are affected so for these little ones you can also see that a lot of the changes
are taking place around the face side of the head because that's part of where that code to build
those structures on everyone lives or is located now see this little girl as well beautiful
as she is a
nd none of us would really look twice and think anything if we saw her
out in the street or out playing or in her classroom how widely set her eyes
are so that is called hyper tellerism and it means that all the children no
matter how strongly affected with this deletion disorder whether they didn't lose
too much genes or whether they lost more jeans are going to end up with this little widely spaced
eyes and that is not coming to them from the rest of the family some families do everybody
has very
nicely widely sleeved eyes but in this case her family does not and we saw the same thing in the
little light-haired girl that was in the first slide for this one so that's called hypertonism
does it make any problems with her vision nope no problems with vision just a slight change to the
build and again what does microcephaly look like it doesn't mean there's no brain it just means
that it's not as large as we would expect it to be that just does generally mean that there are
so
me slowdowns in learning the learning process but it doesn't mean they don't learn it just
means that it's going to take a little bit longer okay so skip down a couple more let's look at a
different example of deletion same thing the loss of a series of triplet code in a particular area
but this time for this one i want us to take a look at something that's much more advanced than
what gregor mendel could have ever studied and something that until very recently uh there
weren't that many re
searchers that actually were particularly aware of it and that's called
genomic imprinting so in this particular case we're going to look at two disorders and again the
people that are affected with them they have lives they just have challenges that those of us that
are genetically standard um don't have to worry about or don't have to um work around for this
so in this case the chromosome is chromosome 15 and again practicing this terminology the q arm
so that's the longer section of the
chromosome so q arm so chromosome 15 q arm it is deletion
so it means a run of code is missing it broke off well it's not on the chromosome anymore if
the chromosome that has the missing run of code came from the father then it produces a set of
phenotypes that we call prodder willie syndrome if that chromosome came in the ovum
and it was from the mother's side then the phenotypes that are produced even though
it's the same area that broke off it doesn't give exactly the same phenotypes or
changes and that's called angelman so what does it really mean it means that
incredibly like i can barely imagine it means that your body knows there's a nice little my
attempt at a nice little sparkle here your body knows if it's all the time i don't think they
can prove it right now but at least at times your body knows and it matters whether the chromosome
was in the ovum or whether the chromosome was in the sperm to begin with incredibly interesting
so again what's broken off what's mi
ssing is this gene run further down on the bottom of
the chromosome if it's missing from the fathers then it activates something else if it's missing
from the mothers then there's a different one you don't need this chart but genomic imprinting
that means that whether the change is on the sperm or the ovum matters and then a couple of
these examples so on this one this particular individual probably all of you recognize or you'll
probably recognize her voice. Mialim Bialik has been a famou
s actor since she was a little child,
and then long-running tv show that's been on TV for a long time and she's very good at all
that, but she's also freaking genius, and she has a PhD in biochemistry. Her doctoral dissertation
actually was specifically on this deletion area on chromosome 15 that produces Prader Willie. So let's
let her explain what the changes are that happen. Hi I'm Mayam Bialik. You may know me as Amy
Farah Fowler from the hit comedy show The Big Bang Theory ,or from th
e tv show Blossom. what some
of you may not know is I have a doctoral degree in neuroscience. while working on my degree
at the university of california los angeles in 2007 I wrote my dissertation on a rare genetic
disorder known as Pradder Willie syndrome or pws. Prader-willi syndrome is the leading cause of
childhood obesity and it affects approximately one in fifteen thousand births. people with this
syndrome constantly feel hungry, they don't have the ability to ever feel full. So w
ithout support
this can lead to life-threatening obesity along with many other medical complications. if not
closely monitored individuals with pws can potentially die from overeating. In addition people
with pws suffer from a number of other symptoms including medical psychological and developmental
challenges as an infant ironically babies with pws are very weak in muscle tone and have no appetite.
So the parent's effort is spent trying to get them to eat. The child's appetite then typ
ically begins
to increase between the ages of two to four years old, at which time the hunger begins to take
over. Imagine every day thinking about food. All the time constantly figuring out when you can
eat next, or how you can get food. Remember a time when you felt your hungriest? Imagine feeling like
that all day, every day, for the rest of your life. Kids with PWS will continue to eat and eat and
gain weight on considerably fewer calories than the average person. If not properly supe
rvised
some individuals can gain up to 20 pounds in one weekend. Parents and caregivers often have to lock
their cabinets and refrigerators to keep their child with PWS from eating. As one eight-year-old
boy said to his parents when he thanked them for locking up food, ' I try and I try but my hand
reaches into the refrigerator and I can't stop it'. Keeping a regimented food schedule, securing food,
and keeping it out of sight, are some of the many ways parents and caregivers are able to
help
minimize the problem and reduce the stress on both themselves and their child. As the child gets
older the food issues in school and everywhere else in society becomes more of a challenge.
sadly in order to save their lives parents have to severely restrict their teen and adult child's
freedom as adults many people with PWS will live in highly structured residential settings, most
with 24 hour a day, seven day a week supervision. but there is hope prader-willi syndrome
association u
sa has been providing life-saving research crisis and medical support education
and newly diagnosed family support since 1975. with a national office in sarasota florida
and chapters all around the country they are saving and transforming the lives
of people with Prader Willie syndrome . okay so i'm going to stop right there because
she's going to go on and do some other social commentary there so again genomic
imprinting you might sometimes also see that as a sex linked disorder. That mean
s that the
body knows if it came in a sperm or an ovum. It doesn't mean that you got it because you had
sex, and it doesn't mean that it comes from the sex chromosomes. It just means that whether it's
carried of contact from one of those or another. So yeah this is I've seen some other programs
on this particular disorder and it is just for those that have the strongest version of it, it's
really really last year because you can bear wsa come on barely imagine what it would be like
to ( s
ee if we can get this to let me leave this) to feel as if you were starving every minute of
every day of your life. And that's really what's happening when they eat their body doesn't tell
the stomach doesn't tell the rest of the body that it's full. The brain never feels satisfied. It
doesn't have sagety and instead what it's doing is running that panic thing that it, because it
cannot tell that you ate. And so they feel like they're starving. So you did notice that she did
quote child
talking and interacting, so verbally fine. Their use of English full sentences.
Good coordination generally for most of them um and that sort of thing. This one again it's
rare, but one in fifteen thousand means it's a lot more common than Cree du Chat. It is um uh
not inherited generally. Generally these are not individuals that someone else in any kind of you
know okay situation would be exchanging gametes with so the iq generally a little bit less than
what we normally see in populat
ion but not so low that they can't um enjoy other things in life one
of the things that does occur though. So she said they started off with low muscle tone - so hypotonia again. This is a normal kind of typical, early on visit back to the doctor with your babies once
they're, you know, weeks old. Where the doctor gently pulls up a little bit and is looking to see that
the baby's gonna want to pull their head forward, or lean them forward this way and the baby wants
to lift the head up and s
ee where they're going. As long as they can do that and they're at the
right age then, that means that they're moving along. Just because they can't do that does not
mean they have a genetic disorder. Again the term just means low muscle tone. so maybe they're not
feeding well, maybe the mom's breast milk doesn't have enough, or it doesn't have enough nourishment
in it ,maybe it's a digestion, maybe they have an infection, maybe something else is going on
there. So and then the last thi
ng these two individuals and the woman that you saw during the
video sitting next to her dog they're not related but you can see how closely similar the shape of
the face is one of the things that's happening with this is it does diminish pigmentation levels
in the hair and eyes and skin so while they aren't albino they don't have as much variety as we might
see in their own general families there and so for some of them because they didn't lose as much of
the broken section on the q in the
15. they're hyperphagia right their drive to continue to eat
so that's what phage means fijia consumption so they're driven to eat too much may fade down
to where they're very interested in food but honestly that's our population and our culture at
this moment anyway we did have a neighbor where one of the family members um did have this genetic
change and he was very social. He would go on walks around the neighborhood, remembered everyone's name.
But not too long into little chat conver
sations, like over the fence, or when you saw while we were
walking the dog, did he ask do you have a snack? Do you have a candy bar in your pocket. Could I
come in your house? And we knew his parents were like oh your mom's gonna be so mad if you come
in the house and you say I know, I know she'll be so mad. I can't go in the house. So um you know
did enjoy life to a certain extent for those individuals. But if it's really bad they do have
to live someplace where they don't smell fo
od, they don't see any ads, they're not having any toys that
look like a plastic hamburger. Where they can just try to forget that as best they can in between
the meals. But it does change some of the coding in the face, and in for pigmentation as well.
Now we're going to skip this one for Angelman . Angelman is the other side of this. So this one
is um sex-linked or linked to maternal 15 code in this case the result is really different. Kust
about the only thing that's similar between
the two - even though it's the same segment- is that loss
of pigmentation. When you see photos, a whole lot of them are very fair-skinned, very very light in
the eyes and hair, even though the parents are not . It doesn't mean they're albinos, it just means
it's going to be lighter than what their family passed on. So developmental delays though in
Angelman are much, much more severe. These children frequently never can speak in sentences. They also
have Ataxia. So Ataxia is a good o
ne for all of us to know. Ataxia is when you have a loss of balance
and that you're not able to neurologically stand up and walk in a straight line and look steady.
So the person might look like they're leaning or they're staggering, or they can't seem to hold. Now
Ataxia is the same word whether you're intoxicated, or whether you've had for instance an accident
that's damaged your brain, and you don't have a functional state of balance anymore.
Ataxia can come from inner ear injuries, or
disorders, and it can be genetic. So
Ataxia = loss of being able to hold your balance. So no speech at all or very minimal. They do have
uh neurological problems where they clench up and their nerves don't fire very well, and they'll
get their little hands up and they'll kind of be shaking, but they almost every photo shows
them with a big smile on the face. uh Smiling and laughing, whether emotionally that's the state
or not I don't know that that's super clear from researching it a li
ttle bit, but it the parents do
think that they're happy enough. Highly social interaction, but because they can't walk around and
they have really severe some other issues with health they will never really be going on walks
and talking to the neighbors in their life. So your baby is going to be your baby for their life.
They're going to need help with everything, eating, using the potty, wearing clothes, knowing
what to do and so on and so forth. So here you can see in this case again
lack
of, some diminishment of pigmentation. And in this case so this is Colin Farrell the actor, and he
does have a child that has Angelman syndrome. And while he does not release photos of
his child or take her out in public, he does help with funding and fundraising for research
and other kinds of things related to this. So Angelman syndrome. Is there any chance that he and
his wife are likely to in any further or partner, I don't know if they're still married, um ever
have this happ
en again to any of their children? This is a random mutation and the chances
it would occur again in the family are virtually zero, and it just randomly happened.
Just one of those things that sometimes shows up. In um Angelman again, neurogenetic
problems, severe nerve issues from them. And one last term that we
learned from today: Strabismus. Strabismus is when your eyes, even though you can see, when
they don't have the nerve or muscle control to cause them to track parallel ahead in
the same
plane all the time. So Strabimus is the term for if your eyes are crossed, or like this child
that you can see at the top where both are kind of leaning out a little bit, or when one is diverting.
Doesn't mean that you can't see. As long as the rest of the message is going through. If your eyes
aren't looking in the way that your brain expects, what the brain does is actually decide which
one it's going to read, and it just stops being confused after a while. That happens sometim
es with
some of those eye surgeries. So for instance if you have real difficulty seeing things that are small,
they fix just one eye. So for a little bit after the surgery it's really confusing if you're trying
to look at a distance, or look up close because your brain doesn't know what to do. And then a few
weeks in when you're looking at little stuff, your brain's just really reading one eye. When you're
looking far away it's really just reading the other eye. Never is it using the t
wo together because
they can't focus on the same stuff. So really interesting stuff. okay we got a little bit of time
left and so we will do the first um little step here for um chromosome numeral abnormality and
then call it a day because you have plenty to do before i see you next monday so chromosome numeral
abnormality means that the individual is born with an extra or a missing chromosome if you have
one that's missing then the term is monosomine right because you don't have it in a p
air you just
have one and if you have an extra it's trisomy these are not particularly common for most chromosomes
except for there is one chromosome pair where trisomy occurs fairly more frequently and
the person has a normal life span and generally not too many outcomes that are really a big
problematic thing for them to divert around us as far as they go through their their lives
we're going to not work on partial and mosaic right at this particular minute but i'll give you
three ones t
hat we'll look at for a little bit on monday when we come back then on monday we'll
look at the rest of chapter five so we're going to look at trisomy 13 which is called pac-tau
syndrome trisomy 18 edward and trisomy 21 down so you all and so many of us are going to um just as
members of communities or perhaps professionally work with people that may um have family
members or on southwestern college when we actually get to go to campus um you have a
number of co-workers that do facilities w
ork on campus usually not so much at the time when it's
the busiest with the traffic and the students but around about noon or so and then through
the late afternoon so i see them all the time where there are some different types of learning
disabilities but um so it isn't always the biggest thing but when you're reading again about
meiosis and the meiosis um video non-disjunction where does this type of error come from it
comes from errors that occur during gamete formation so it's not in
the parents in most
cases it's just something that happens when the chromosome makes its copy right so then
it's in the x form with chromatids and then when it's supposed to let go of the copy right the
centromere should dissolve and let the copy go it doesn't dissolve in time and so one of the cells
brings two into it and the other cell is missing that chromosome so that's called non-disjunction
okay this has been pretty intense amount of stuff i know you have lots to do most students have
not posted your visual class activity yet today so please work on that and turn that in by the
end of day that's worth 10 points and there's because it's been up for a number of days there's
no reason to be turning it in late so and then be sure and i'll send you a little nagging reminding
email before the end of the week to come and pick up your to come and finish um
with taking the quiz for that one
Comments