A family visits a pediatrician with their sick child. The four...

Question

A family visits a pediatrician with their sick child. The four-month-old baby is pale, has obvious episodes of pain, and is not thriving. The doctor orders a series of blood tests, including a test for hemoglobin types. The results show that the infant is not only anemic but that the anemia is due to sickle-cell anemia. The family wants to know if their other two children have sickle-cell anemia, sickle-cell trait, or no sickle-cell gene at all.
a. What test will be used?

a. What test will be used?

Accepted Answer

Hi, everyone. Here is the next question. It says a person suffering from sickle cell anemia may experience yellowing of the skin, swelling in the hands and feet, recurring pain and eyesight problems. A series of blood tests and a test to identify hemoglobin types are done to diagnose whether the anemia is caused by sickle cell anemia, which lab test determines if a person has sickle cell anemia, has a sickle cell trait or lacks the sickle cell gene. So to think about what type of lab test we'd want to think about that cause of sickle cell anemia and what is going on at the protein level. So we may recall that sickle cell anemia is caused by a mutation that changes a single amino acid in the hemoglobin protein. So it causes the amino acid glutamate or glue to be replaced by veiling. I put abbreviated vowels. Why does this single amino acid substitution cause such a cascade of symptoms such as severe disease? Well, for that, we want to look at the R groups of these two. So the R group for glutamate is ch two, ch two coo minus at neutral PH S. This is a carboxylic acid group that is a carboxylate at a neutral Ph H it has api of 3.2. So it is a charged molecule at bodily ph. Now let's look at bailing, bailing to our group is CH and then in parentheses, ch three CH three. So it's this three carbon branched isopropyl chain. So this is an al keel group. So this is a nonpolar molecule. Well, if we think about protein structure, protein folding, all of that three dimensional structure is caused by interactions between the R groups. Replacing a negatively charged amino acid with a nonpolar amino acid is going to cause big differences in the folding of the protein. And indeed, in this case, the replacement with valen ends up causing the sort of linkage that makes the blood cells go from this flexible donut shape to a rigid sickle shape. And that then causes all of the symptoms that categorize sickle cell. So we need to look at blood tests to identify if a person has sickle cell anemia, the sickle cell trait or lacks the sickle cell gene. Well, this is because to have the disease, two copies of the gene need to be inherited from both parents or one copy from each parent. So two copies need to be inherited. So all the hemoglobin, we have that glue to vowel substitution. So it's a recessive genetically inherited disease to have the trait, one copy of the gene is inherited from one parent. So half of the hemoglobin in the body will have that glue to vowel mutation while the other half will be normal but half normal. And then of course, if they don't have the disease at all, all of the hemoglobin has the glutamate residue, so how would we distinguish between these three states? Well, the answer comes back to the structure of that R group glutamate has a negative charge, vine has no charge. So there will be a difference in charge of the hemoglobin. How do we separate molecules that have different charges? We would use electrophoresis. So we run them on a gel, run an electric current through it, they migrate through at different rates depending on their charge. So you could separate blood samples that have whether a person that doesn't have the disease or even have the gene, a person that just has one copy and a person that has two copies because their hemoglobin will have a different charge. And obviously, if they have the disease, all of their hemoglobin will have this extra negative char. Uh the ex excuse me, all of the hemoglobin will have the extra polar molecule. So it will be have less negative a person without the gene at all. So and while the person with no sickle cell gene will have the most negatively charged protein, a person with disease will have the least negatively charged protein and a person with the sickle cell trait. So just one copy will be in between. Also the shape of the protein will affect how it runs on the gel. So between the shape and the charge, these three different varieties will separate on an electrophoresis gel. So when we look again at what our question asks us, the lab test, we would be looking for to distinguish between a person who has sickle cell anemia, has the sickle cell trait or lacks a sickle cell gene would be electrophoresis, being able to separate those different hemoglobin proteins. See you in the next video.

Key Concepts

Sickle-Cell Anemia

Hemoglobin Electrophoresis

Genetic Inheritance Patterns

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