Another thing we covered in quite a lot of detail are mutations,
chromosome mutations and point mutations.
So, I wanted to take a quick review here of how much of an
impact a point mutation can have. This would be
more specifically found in single-gene disorders.
So point mutations will involve changing a particular amino acid.
Here, you can see a string, part of the string of the
amino acid chain and the nucleotides that code for it for
hemoglobin B. You might recall that the hemoglobin molecule
is made up of two alpha subunits and then
two beta subunits. The problem can be in the mutation associated
with the sickle cell just one nucleotide difference.
We looked in this in a fair amount of detail before such that
we see a substitution of valine for glutamine.
When we do that, it changes the form of hemoglobin such that
the beta subunits will sickle or they’ll fold
in arm’s fold because they have a valine which has a
different electronegativity than the glutamine.
That causes the hemoglobin molecules to stack up.
The hemoglobin molecules inside the red blood cells will
cause them to sickle like this over here. So, that’s an example
of a point mutation. Recall, there are a few different
types of point mutations. We’re going to look at three of
them here involving single nucleotides. You could have a
silent mutation. A silent mutation is where we see that
the amino acid isn’t changed at all even though one of the
nucleotides is changed. So in this case, a U became a C
and then we could have a nonsense mutation in which
it codes for a stop codon. So instead of having a U in that spot,
we have an A in that spot. It is nonsense because
we get no more amino acids. Obviously, that’s going to have
a more significant phenotypic effect or we could have
a missense mutation which is like the hemoglobin B mutation
that we just took a look at. That would result
in having a different amino acid which may have a different polarity.
I said electronegativity earlier. I didn’t mean that
but a different polarity to the molecules, so it folds
differently and has some of the phenotypic effects.
So, point mutations can actually result in a frameshift mutation.
For instance, if we insert a particular base
or we delete a particular base, then you’re shifting the
reading frame by one nucleotide or two nucleotides
or three nucleotides. We will be looking at some situations
where three nucleotides get inserted. That’s the case
of the triplet repeat expansion. That’s significant to
a couple of very important genetic disorders. So, if we insert
this CAG repeat and it repeats and repeats and for
some unknown reason, these repeats will expand
from generation to generation in diseases like Huntington’s
disease and Fragile X. So, the triplicate repeat will come up as
a point mutation that will not quite fit the Mendelian
inheritance patterns that we’ve been talking about.
Then we look at chromosomal mutations. Again,
we’ve seen this before. But they’re going to come into play
fairly significantly during this course as we look at regions
that are deleted. We end up with a chromosome
that is different. We could have a section that is duplicated.
Sometimes this happens from uneven crossing over
during prophase I of meiosis. But it can happen in other means
too with transposable elements, translocations
of pieces of genome. So deletions and duplications and then
we might even have inversions where one piece
actually gets clipped out and moved and flipped back in upside down.
So, you can see that the outcome is different
chromosomes than we had initially. If these sorts of
things happen within a gene, we may see point mutation
but most generally, we’re going to see chromosomal mutations
or duplications, deletions, and inversions
on a much larger scale. So, we call them chromosomal
mutations. The final chromosomal mutation that we’ll
be considering are reciprocal translocations. That’s
when we have two chromosomes that exchange reciprocally.
However, they are not homologous chromosomes. So, we end up
with completely different chromosomal products.
You can see here, the top and the bottom chromosomes are
different for some reason. Maybe it’s one chromosome's
contacting another or maybe there’s a transposable element
or some things moved and pieces are reciprocally exchanged
between non-homologous chromosomes. We end up with
different gene products. The effect that they have
really depends on where this translocation happens.
We’ll look at a particular example of reciprocal translocation.
We’ll look at in much more detail later on during the course.
So, thank you so much for listening.
I look forward to seeing you as we explore these types of
mutations throughout the rest of the course.