Question
Sickle Cell Disease
1
Sickle cell disease is the most common inherited blood disorder in the United States. It affects about 80,000 Americans. In the United States, African Americans are most frequently affected by sickle cell disease. About one in 12 African Americans and about one in 100 Hispanic Americans carry the sickle cell trait.
What Causes Sickle Cell Disease?
2
Sickle cell disease is caused by a mutation in the hemoglobin-Beta gene. This gene is responsible for the creation of a protein called beta-globin. Beta-globin is part of a larger protein called hemoglobin that is found in red blood cells. Figure 1 shows how a single gene mutation causes a significant change to the beta-globin protein units that form the structure of hemoglobin.
Figure 1 – A single mutation in the D-N-A sequence of a gene results in a significant change in the shape of the red blood cell. For a normal cell and a sickle cell, the following parts are described: partial D-N-A sequence of hemoglobin-beta gene, partial R-N-A sequence, partial amino acid sequence for beta-globin protein, hemoglobin molecule, and a cross-section of a red blood cell. Normal – partial D-N-A sequence is C-C-T bonds with G-G-A, G-A-G bonds with C-T-C, G-A-G bonds with C-T-C; partial R-N-A is C-C-U, G-A-G, G-A-G; Partial amino acid sequence is pro, glu, glu; Hemoglobin molecule is 4 circles forming a square and shaded light and dark, alternatively; cross-section of a red blood cell is half-a-disk with dots labeled normal hemoglobin. Sickle cell – partial D-N-A sequence is C-C-T bonds with G-G-A, G-T-G bonds with C-A-C, G-A-G bonds with C-T-C; partial R-N-A is C-C-U, G-U-G, G-A-G; Partial amino acid sequence is pro, val, glu; Hemoglobin molecule is 3 sets of 4 circles forming a crooked square and shaded light and dark, alternatively; cross-section of a red blood cell is a flat, long half-disk with dots labeled abnormal hemoglobin forms strands that cause sickle shape.
3
Normally, A is the fifth letter in the DNA sequence for this part of the hemoglobin-Beta gene. See the top line of letters in figure 1. This coding normally specifies the amino acid glutamic acid (Glu) in that place in the beta-globin protein. If the A changes to a T, the new amino acid specified in that place is valine (Val). This change in the beta-globin protein leads to an abnormally long hemoglobin molecule.
4
In people with sickle cell disease, abnormal hemoglobin molecules—hemoglobin S—stick to one another. They form long, rod-like structures. These structures cause red blood cells to become stiff. They assume a sickle shape. Red blood cells with normal hemoglobin (hemoglobin-A) are smooth and round. They easily glide through blood vessels. The sickle shape causes the red blood cells with abnormal hemoglobin to pile up.
Effects of Sickle Cell Disease
5
Sickle cells are destroyed rapidly in the bodies of people with the disease. This causes anemia, a shortage of healthy red blood cells. Anemia can produce symptoms such as pale skin, weakness, and headaches. Severe cases of anemia can lead to heart attacks. This anemia is what gives the disease its commonly known name—sickle cell anemia.
6
Sickle cells that pile up can cause blockages and damage vital organs and tissue. Sickle cells can result in lung tissue damage that causes a condition called acute chest syndrome. These abnormal cells also damage the spleen, kidneys, and liver. Damage to the spleen makes patients—especially young children—easily overwhelmed by bacterial infections.
Inheritance of Sickle Cell Disease
7
A baby born with sickle cell disease inherits the mutated hemoglobin-Beta gene for the disorder from both parents. When both parents have the genetic defect, there is a 25 percent chance that each child will be born with sickle cell disease.
8
If a child inherits only one copy of the defective gene (from either parent), there is a 50 percent chance that the child will carry the sickle cell trait. People who only carry the sickle cell trait typically don't get the disease. However, they can pass the defective gene on to their children.
Diagnosing Sickle Cell Disease
9
Doctors diagnose sickle cell disease through a blood test that checks for hemoglobin S—the defective form of hemoglobin. To confirm the diagnosis, a blood sample is examined under a microscope to check for large numbers of sickled red blood cells. In more than 40 states, testing for the defective protein that causes people to develop sickle cell disease is routinely performed on newborns.
Gene Therapy: Hope for a Cure
10
Researchers are experimenting with attempts to cure sickle cell disease using gene therapy. They correct the defective gene and then insert it into the bone marrow of those with sickle cell disease. This, they hope, will prompt the body to produce normal hemoglobin. Recent experiments show promise. In December 2001, scientists at Harvard Medical School and MIT announced that they had corrected sickle cell disease in mice using gene therapy.
11
Researchers bioengineered mice so that their genetic material contained the defective human hemoglobin-Beta gene that causes sickle cell disease. Bone marrow containing the gene was removed from some of the mice and genetically "corrected." This was done by adding a copy of the human hemoglobin-Beta gene that researchers altered. This altered gene inhibits the production of abnormal hemoglobin that causes cells to assume a sickle shape.
12
Then, researchers removed the bone marrow from some of the other bioengineered mice. The “corrected” marrow was transplanted into these mice. The mice with sickle cell disease began producing high levels of normal red blood cells. They also showed a large reduction in sickle cells. Scientists are hopeful that this technique could also be used to help people with sickle cell disease.
The Punnett square below represents the possible genotypes for the offspring of one parent with two copies of the defective sickle cell gene (genotype: aa) and one parent without the defective gene (genotype: AA). Drag and drop the genotypes that BEST complete the Punnett square into the boxes. Answers can be used once, more than once, or not at all.
1
Sickle cell disease is the most common inherited blood disorder in the United States. It affects about 80,000 Americans. In the United States, African Americans are most frequently affected by sickle cell disease. About one in 12 African Americans and about one in 100 Hispanic Americans carry the sickle cell trait.
What Causes Sickle Cell Disease?
2
Sickle cell disease is caused by a mutation in the hemoglobin-Beta gene. This gene is responsible for the creation of a protein called beta-globin. Beta-globin is part of a larger protein called hemoglobin that is found in red blood cells. Figure 1 shows how a single gene mutation causes a significant change to the beta-globin protein units that form the structure of hemoglobin.
Figure 1 – A single mutation in the D-N-A sequence of a gene results in a significant change in the shape of the red blood cell. For a normal cell and a sickle cell, the following parts are described: partial D-N-A sequence of hemoglobin-beta gene, partial R-N-A sequence, partial amino acid sequence for beta-globin protein, hemoglobin molecule, and a cross-section of a red blood cell. Normal – partial D-N-A sequence is C-C-T bonds with G-G-A, G-A-G bonds with C-T-C, G-A-G bonds with C-T-C; partial R-N-A is C-C-U, G-A-G, G-A-G; Partial amino acid sequence is pro, glu, glu; Hemoglobin molecule is 4 circles forming a square and shaded light and dark, alternatively; cross-section of a red blood cell is half-a-disk with dots labeled normal hemoglobin. Sickle cell – partial D-N-A sequence is C-C-T bonds with G-G-A, G-T-G bonds with C-A-C, G-A-G bonds with C-T-C; partial R-N-A is C-C-U, G-U-G, G-A-G; Partial amino acid sequence is pro, val, glu; Hemoglobin molecule is 3 sets of 4 circles forming a crooked square and shaded light and dark, alternatively; cross-section of a red blood cell is a flat, long half-disk with dots labeled abnormal hemoglobin forms strands that cause sickle shape.
3
Normally, A is the fifth letter in the DNA sequence for this part of the hemoglobin-Beta gene. See the top line of letters in figure 1. This coding normally specifies the amino acid glutamic acid (Glu) in that place in the beta-globin protein. If the A changes to a T, the new amino acid specified in that place is valine (Val). This change in the beta-globin protein leads to an abnormally long hemoglobin molecule.
4
In people with sickle cell disease, abnormal hemoglobin molecules—hemoglobin S—stick to one another. They form long, rod-like structures. These structures cause red blood cells to become stiff. They assume a sickle shape. Red blood cells with normal hemoglobin (hemoglobin-A) are smooth and round. They easily glide through blood vessels. The sickle shape causes the red blood cells with abnormal hemoglobin to pile up.
Effects of Sickle Cell Disease
5
Sickle cells are destroyed rapidly in the bodies of people with the disease. This causes anemia, a shortage of healthy red blood cells. Anemia can produce symptoms such as pale skin, weakness, and headaches. Severe cases of anemia can lead to heart attacks. This anemia is what gives the disease its commonly known name—sickle cell anemia.
6
Sickle cells that pile up can cause blockages and damage vital organs and tissue. Sickle cells can result in lung tissue damage that causes a condition called acute chest syndrome. These abnormal cells also damage the spleen, kidneys, and liver. Damage to the spleen makes patients—especially young children—easily overwhelmed by bacterial infections.
Inheritance of Sickle Cell Disease
7
A baby born with sickle cell disease inherits the mutated hemoglobin-Beta gene for the disorder from both parents. When both parents have the genetic defect, there is a 25 percent chance that each child will be born with sickle cell disease.
8
If a child inherits only one copy of the defective gene (from either parent), there is a 50 percent chance that the child will carry the sickle cell trait. People who only carry the sickle cell trait typically don't get the disease. However, they can pass the defective gene on to their children.
Diagnosing Sickle Cell Disease
9
Doctors diagnose sickle cell disease through a blood test that checks for hemoglobin S—the defective form of hemoglobin. To confirm the diagnosis, a blood sample is examined under a microscope to check for large numbers of sickled red blood cells. In more than 40 states, testing for the defective protein that causes people to develop sickle cell disease is routinely performed on newborns.
Gene Therapy: Hope for a Cure
10
Researchers are experimenting with attempts to cure sickle cell disease using gene therapy. They correct the defective gene and then insert it into the bone marrow of those with sickle cell disease. This, they hope, will prompt the body to produce normal hemoglobin. Recent experiments show promise. In December 2001, scientists at Harvard Medical School and MIT announced that they had corrected sickle cell disease in mice using gene therapy.
11
Researchers bioengineered mice so that their genetic material contained the defective human hemoglobin-Beta gene that causes sickle cell disease. Bone marrow containing the gene was removed from some of the mice and genetically "corrected." This was done by adding a copy of the human hemoglobin-Beta gene that researchers altered. This altered gene inhibits the production of abnormal hemoglobin that causes cells to assume a sickle shape.
12
Then, researchers removed the bone marrow from some of the other bioengineered mice. The “corrected” marrow was transplanted into these mice. The mice with sickle cell disease began producing high levels of normal red blood cells. They also showed a large reduction in sickle cells. Scientists are hopeful that this technique could also be used to help people with sickle cell disease.
The Punnett square below represents the possible genotypes for the offspring of one parent with two copies of the defective sickle cell gene (genotype: aa) and one parent without the defective gene (genotype: AA). Drag and drop the genotypes that BEST complete the Punnett square into the boxes. Answers can be used once, more than once, or not at all.
Answers
GPT-4o mini
To complete the Punnett square, we need to understand the genotypes of the parents.
- One parent has two copies of the defective sickle cell gene (homozygous recessive) with genotype **aa**.
- The other parent does not have the defective gene (homozygous dominant) with genotype **AA**.
When creating a Punnett square, we place one parent's alleles on one side and the other parent's alleles on the other side. We'll arrange it as follows:
```
A A
------------
a | Aa | Aa |
------------
a | Aa | Aa |
------------
```
Now, filling in the squares:
- The alleles from the first parent (aa) are **a** and **a**.
- The alleles from the second parent (AA) are **A** and **A**.
Therefore, all offspring will have the genotype **Aa**, meaning they carry the sickle cell trait but do not have the disease.
So, the completed Punnett square contains:
- All four squares will have **Aa** in them.
In summary, the genotype that BEST completes the Punnett square is **Aa** for all boxes.
- One parent has two copies of the defective sickle cell gene (homozygous recessive) with genotype **aa**.
- The other parent does not have the defective gene (homozygous dominant) with genotype **AA**.
When creating a Punnett square, we place one parent's alleles on one side and the other parent's alleles on the other side. We'll arrange it as follows:
```
A A
------------
a | Aa | Aa |
------------
a | Aa | Aa |
------------
```
Now, filling in the squares:
- The alleles from the first parent (aa) are **a** and **a**.
- The alleles from the second parent (AA) are **A** and **A**.
Therefore, all offspring will have the genotype **Aa**, meaning they carry the sickle cell trait but do not have the disease.
So, the completed Punnett square contains:
- All four squares will have **Aa** in them.
In summary, the genotype that BEST completes the Punnett square is **Aa** for all boxes.