Genetics Sickle Cell SH

The Genetics of Sickle Cell Anemia and Sickle Cell Trait[footnoteRef:1] [1: By Dr. Ingrid Waldron, Dept. Biology, Univ. Pennsylvania, © 2020. This Student Handout and Teacher Notes are available at https://serendipstudio.org/exchange/bioactivities/geneticsSCA.]

Sickle Cell Anemia

Red blood cells are full of hemoglobin, the protein that carries oxygen. Normal hemoglobin dissolves in the watery cytosol of the red blood cell. Red blood cells with normal hemoglobin are disk-shaped and flexible, so they can squeeze through the smallest blood vessels (Figure A).

In contrast, sickle cell hemoglobin tends to clump into long rods that cause the red blood cells to be shaped like a sickle or a banana (Figure B). These sickle cells can block blood flow, which causes pain and damage to body organs. In addition, the sickle cells do not survive as long as normal red blood cells, so there are fewer red blood cells in the blood. This anemia can lead to a feeling of low energy. Thus, sickle cell hemoglobin causes the symptoms of sickle cell anemia.

To learn more, view the video, “How This Disease Changes the Shape of Your Cells”, available at

https://www.youtube.com/watch?v=hRnrIpUMyZQ

1. Complete this flowchart by filling in the intermediate steps that describe how sickle cell hemoglobin can cause pain, damage to body organs, and anemia.

→

→

→

Pain + damage to body organs

Sickle cell hemoglobin

Anemia (low red blood cells)

This chart shows how two alleles of the hemoglobin gene determine whether a person has sickle cell anemia.

Genotype

Protein

Phenotype (characteristics)

HH

Normal hemoglobin dissolves in the cytosol of red blood cells.

Disk-shaped red blood cells normal health

hh

Sickle cell hemoglobin tends to clump in long rods inside red blood cells.

Banana-shaped red blood cells pain, damage to body organs, and anemia = sickle cell anemia

2. Describe how the hh genotype can result in banana-shaped red blood cells.

Sickle Cell Trait

A person who is heterozygous for the sickle cell allele has sickle cell trait. In a heterozygous Hh person, each red blood cell has roughly half sickle cell hemoglobin and half normal hemoglobin. The normal hemoglobin in the red blood cells prevents the sickle cell hemoglobin from forming long rods. As a result, people with sickle cell trait almost never experience the pain, organ damage and anemia that occur in sickle cell anemia.

3. What evidence supports the claim that the H allele is dominant and the h allele is recessive?

Although the H allele is described as dominant, heterozygous Hh people do not have exactly the same phenotype as homozygous HH people. Heterozygous Hh people have less severe malaria infections than homozygous HH people. The malaria parasite, which infects red blood cells, cannot reproduce as well if the red blood cells contain sickle cell hemoglobin. This explains why people with sickle cell trait have less severe malaria.

4. Complete this chart to describe how each allele in a heterozygous Hh person influences his or her phenotype.

Allele

Protein

How This Protein Affects the Hh Phenotype

H

h

5. A single gene often affects more than one phenotypic characteristic. For example, multiple phenotypic characteristics are affected by the different genotypes of the hemoglobin gene. Support this claim by completing the table below. (For the second column, remember that H = allele for normal hemoglobin and h = allele for sickle cell hemoglobin.)

Three Different Phenotypic Effects that the Alleles of the Hemoglobin Gene Can Have

Genotype of Person Where This Phenotypic Effect has been Observed

Inheritance of the Sickle Cell Allele

This pedigree chart shows the inheritance of sickle cell anemia in three generations of a family. Each male is symbolized by a square (□) and each female is symbolized by a circle (○). A person who has sickle cell anemia is symbolized by a dark square or circle. The couple labeled 1 and 2 had five children, including one daughter with sickle cell anemia (5). The son labeled 3 and his wife (4) had four children, including one son with sickle cell anemia (6).

6. Explain how a person can inherit sickle cell alleles from parents who do not have sickle cell anemia. Include a Punnett square for parents 1 and 2 in your answer.

7. In the pedigree, write the genotypes of each person who is labeled with a number.

8a. If parents 3 and 4 had another child, what is the probability that this child would have sickle cell trait? 0%___ 25% ___ 50% ___ 75%___ 100%___

8b. Explain your reasoning.

A model is a simplified representation of a complex biological process. A model does not include all of the features of the process it represents; instead, the model highlights certain key features of the process. For example, pedigree charts and Punnett squares provide different types of information about inheritance.

9a. Compare pedigree charts with Punnett squares. What is an advantage of a pedigree chart as a model of inheritance?

9b. What are some advantages of Punnett Squares as a model of inheritance?

Challenge Questions

10. Currently, all newborns in the US are tested for sickle cell anemia and sickle cell trait. Before 2006, some newborns were not tested. If a person has sickle cell anemia, he or she will usually experience symptoms that will lead to a diagnosis. However, a person who has sickle cell trait often is unaware of this condition, unless he or she has been tested. Explain why.

In the US, people with sickle cell trait have the same life expectancy as the general population. However, people with sickle cell trait have an increased risk of some health problems. For example, people with sickle cell trait have a greater risk of sudden death during extremely strenuous exercise (e.g. Division I football or basic training in the military). These deaths are very rare, but tragic when they occur. Sudden death can almost always be prevented if the exercising person consumes adequate fluids and avoids excessive overheating. These same precautions are important to prevent sudden death for people who don't have sickle cell trait.

11. What do you think is the best way to reduce the risk of sudden death for people with sickle cell trait? Should athletes and military recruits be tested for sickle cell trait? Explain your reasoning.

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