in this video, we're going to begin our discussion on sickle cell anemia. So most of you guys have probably heard of sickle cell anemia before in your previous biology courses. And so recall that sickle cell anemia is a disease that's due to a hemoglobin mutation. And this hemoglobin mutation causes the red blood cells to take on a sickle shape that ultimately causes health issues. And we'll talk more about these health issues a little later in our course. Now, recall that the term anemia is just referring to low number of a re throw sites or low number of red blood cells in patients that have sickle cell anemia. Now again, sickle cell anemia diseases due to a hemoglobin mutation. And more specifically, it's due to a Homo Zegas point mutation in the DNA for the gene that codes for the beta subunits of hemoglobin, ultimately changing the amino acid residue at the sixth position of the beta sub unit from a glue tomate residue to a valin amino acid residue. And so this six year after the three letter codes is just referring to the fact that it's the amino acid residue at the sixth position of the basis of the unit that's being affected. And so we're able to see this down below in our image where on the top half of our image, we have the normal conditions. And then on the bottom half, we have the conditions that cause sickle cell anemia. And so notice that the DNA is being shown here for the normal conditions and, uh, through transcription were able to get in our DNA molecule through translation, were able to get our amino acid, uh, chain, and notice that at the sixth position specifically here, we would have a glutamate amino acid residue under normal conditions and that would lead to normal protein folding and get results in the normal hemoglobin molecule, which we would refer to as a H B A. Under normal conditions to refer to the normal adult hemoglobin, the A could be referred to as adult, and so with sickle cell anemia noticed that it's due to a single Homo zegas point mutation in both copies of the gene that codes for the beta subunits of hemoglobin and so down below here noticed that there is just a flip flop of the A and the T from up above. And this single point mutation is what leads to all of the complications that air caused by sickle cell anemia. And so, through transcription, we get a different RNA molecule. And so instead of having an A in the center nucleotide here, we would actually have a you, uh, in the RNA because remember that, uh, teas are replaced with use in the RNA. And so let's actually make this RNA here a red color for the red color that we have here. And so through translation noticed that instead of getting a glutamate residue, if we were to use the genetic code and this Arna code on here, we would actually get a veiling amino acid residue at the sixth position and recall that glutamate has a negative charge on it, whereas veiling is a neutral amino acid residue. And so because it's neutral, it's going to alter the protein folding. And so notice that, uh, this little nudge coming out represents, uh, the mutated hemoglobin with an altered protein folding here. And so the mutated hemoglobin we're going to refer to as H. B s for the hemoglobin, um, that causes sickle cell anemia and So really, what's amazing to note here is that again, all of the complications of sickle cell anemia is due to just this one swap of the nucleotides. Uh, this one mistake leads to all of the sickle cell complications, which is very incredible to think about how we can, ah, get diseases through such a small change in our DNA. So we'll be able to talk mawr details about sickle cell anemia as we move forward in our course. So I'll see you guys in our next video.
Sickle Cell Anemia
Play a video:
Was this helpful?
So now that we've refresh our memories, that sickle cell anemia is the result of a home a six point mutation. In this video, we're going to talk about how a gluten nation of the mutated hemoglobin molecules actually causes sickle cell anemia. And so the mutation above from our previous lesson video actually leads to the A gluten nation, which is really just a fancy word for the clumping of these mutated hemoglobin chains due to the hydrophobic effect. And so notice down below. We're showing you guys these mutated hemoglobin molecules. And of course, these little pink protrusions here represent the mutated amino acid residue, which is availing residue in the mutated hemoglobin and recall that veiling is a non polar amino acid and non polar molecules are able to form interactions with each other via the hydrophobic effect. And so notice that we have these hemoglobin molecules clumping together essentially a glued in ating, and they can actually create thes long chains of mutated hemoglobin and um, ultimately, this mutated hemoglobin chains can result in the sickle cell anemia shape. And so, fortunately, hemoglobin, oxygen affinity and Alice Derek properties are unaffected even in this mutated hemoglobin however, the mutated hemoglobin chains here, um, or aggregates can deform the red blood cell, causing this sickle cell shape that we see here. And so, uh, notice that we have the sickle cell shape right next to a normal red blood cell here so that you can compare the shapes. And really, it's this shape of the sickle cell, um, red blood cell here that is going to cause most of the complications the health complications associated with sickle cell anemia and so down below. Right here we can say that mutated hemoglobin clumps and causes sickle cell anemia. And so now that we can better understand exactly how mutated hemoglobin molecules can lead Teoh, a sickle cell shape on our next video will be able to talk about, uh, the exact, uh, complications that thes sickle cells can cause health wise. So I'll see you guys in that video.
The amino acid substitution of Val for Glu in Hemoglobin S (sickle-cell hemoglobin) is problematic because it substitutes a _________________ amino acid residue with a _________________ amino acid residue.
Polar ; nonpolar.
hydrophobic ; charged.
Aromatic ; Polar.
Nonpolar ; aromatic.
In sickle cell anemia, the molecular basis of the malfunction of the hemoglobin molecule is:
Faulty binding of iron by the heme groups.
Insufficient iron in the diet.
Substitution of a single amino acid in the DNA sequence.
Reduced affinity for oxygen.
Silent mutation in the DNA sequence causing a single amino acid substitution.
Point mutation in the DNA sequence causing a single amino acid substitution.
Sickle Cell Anemia
Play a video:
Was this helpful?
in this video, we're going to talk about the physiological effects of sickle cell anemia. So the sick old red blood cells are actually more susceptible to becoming trapped in small blood vessels. And if the cycled red blood cells do become trapped in these small blood vessels that can impair blood circulation throughout the body. And of course, impaired blood circulation can cause organ damage. Also, the singled red blood cells are more susceptible to rupturing. And so they rupture. Ah, lot more easily than normal red blood cells leading to anemia, which is again low red blood cell count and so down below. In our example, we can see this sickle cell anemia, physiological effects, and so notice that we're showing you the normal red blood cells as thes circles and the sickle shaped red blood cells as the sickle shape. And so notice that the normal red blood cell will have a normal red blood cell count and there's going to be proper flow through small blood vessels. However, notice that with sickle cell anemia that there is going to be quite a low red blood cell count essentially anemia, due to the fact that again the sick. Old red blood cells can rupture more easily. But there's also the chance for impaired circulation, which is also referred to as occlusion. And so occlusion is just this idea of blockage of blood vessels. And so, of course, that is going to lead to organ damage can cause many different health complications. So even though sickle cell anemia is mainly associated with health complications and some scenarios and some populations in the world, sickle cell anemia can actually be a beneficial thing toe a population. So we'll be able to talk about that mawr in our next video. So I'll see you guys in that video.
Sickle Cell Anemia
Play a video:
Was this helpful?
in this video, we're going to talk about how sickle cell anemia can actually provide resistance to malaria. And so recall from our previous lesson videos, we said that sickle cell anemia was caused by a Homo Zeitgeist point mutation, meaning that both copies of the gene were mutated. However, head arose, I guess individuals for sickle cell trait, meaning that they only have one copy of the gene that's mutated, actually have resistance to malaria. But they do not have sickle cell health issues. And so hetero Zika sickle cell trait because they have resistance to malaria and do not have sickle cell health issues are actually selected for by natural selection in areas of the world with ah high prevalence of malaria. Now, the exact mechanism of malaria resistance is not yet fully understood. So we're not going to talk about this in our course now. Notice down below in our image on the left hand side, the normal alil, or the normal version of the gene for hemoglobin, is represented by a capital A And then, of course, the sickle cell Alil, or the mutated version of the gene for hemoglobin, is represented by a lower case a bold ID and in red like this. And so a home, a zegas normal individual would have two copies of the normal a Leo. And so they are going to have normal red blood cells like what we see here. And so they're not going to have sickle cell disease. However, they're going to be fully susceptible to malaria. And so, in an area of the world with a high prevalence of malaria, having being Hamas AG is normal is actually not going to be beneficial because it is susceptible to malaria, and again, that is going to cause complications. Now, on the other hand, Hamas egas mutant, uh, individuals which have two copies of the sickle cell olio. Uh, they are obviously going to have severe sickle cell disease, Just like what we can see in this image. Their cells are going to be sickle shape, and, uh, however, even though they do have severe sickle cell disease, they're going to have resistance to malaria. And so resistance to malaria is going to be good in an area of the world. Um, that has a high prevalence of malaria. But having severe sickle cell disease is still not a good thing. So this is not beneficial at all. However, a hetero zegas individual would have one copy of the normal Khalil and one copy of the sickle cell. Alil would only have mild sickle cell disease or not have sickle cell health issues at all. Uh, and they do still have resistance to malaria. And so this ah, header Zegas individual is actually going to be beneficial in an area of the world that has a high prevalence of malaria. And so this would be the preferred, uh, in a new area of the world with lots of malaria. And so over here on the right, what we have is a little image toe help you guys see how this little structure right here represents the parasite that causes malaria, and it infects red blood cells. And so you can see that this parasite that causes malaria saying this looks like a healthy cell I can infect, and so the malaria parasite will infect normal, healthy red blood cells. However, over here you can see we have the sickle cell and it says I'll get nowhere if I infect this cell right here. And so notice that having hetero zegas being hetero Saugus for the sickle cell trait. You do have some sickle cell, uh, shaped blood cells, and that is going to help provide at least some resistance to malaria, more so than if you had all normal red blood cells. And so this year concludes our lesson on how malaria resistance is related to sickle cell anemia, and we'll be able to get some practice utilizing these concepts that we've learned in our next few videos, so I'll see you guys there.
Match the following key terms with their appropriate image (A or B):
a) HbS: Image _____
b) HbA: Image _____
c) Malaria resistance: Image _____
d) Heterozygous (Aa): Image _____
e) Homozygous (AA): Image _____
f) Low RBC count: Image _____
g) RNA sequence GAG: Image _____
h) RNA sequence GUG: Image _____
Was this helpful?
Researchers investigating the sickle-cell mutation want to separate the mutant hemoglobin protein (HbS) from the normal adult hemoglobin (HbA) that was extracted from a heterozygous patient’s blood serum sample. In order to do this, they perform gel electrophoresis at a pH of 8.5, where most normal hemoglobin proteins are negatively charged. The protein sample is added to the negative pole and migrates towards the positive pole when current is applied. The result of the gel is shown below. Label which band represent HbS and which band represents HbA.