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Sickle Cell Anemia: Blood Video Questions and Translation Practice Worksheet

Blood video/Sickle Cell Background

After watching the video Blood is Life and reading the handout Sickle Cell Anemia and Genetics: Background Information, answer the following questions.

1. Rosalyn has sickle cell anemia. Describe her symptoms.

 

2. Describe the structure of hemoglobin. (How many chains are there? What types? Why is iron necessary for blood?)

 

3. How does sickle hemoglobin differ from normal hemoglobin?

 

Sickle Cell at the Molecular Level

In sickle cell anemia, there is a mutation in the gene that encodes the b chain of hemoglobin. Within this gene (located on Chromosome 11), ONE BASE in the DNA is replaced with another base, and this mutation causes the normal amino acid #6 to be replaced by another amino acid.

1. Making a Normal Beta Chain of Hemoglobin

The sequence below is the first part of the DNA sequence for the b chain of normal hemoglobin. Fill in the complementary DNA strand using the base-pairing rules for making DNA (A pairs with T, C pairs with G).

DNA: GTG CAC CTG ACT CCT GAG GAG

DNA:

Now make the messenger RNA from the new, complementary strand of DNA that you just wrote down. Use the RNA base-pairing rules (same as DNA but use U instead of T).

mRNA:

Now, using the Genetic Code chart in your textbook, translate this mRNA into a sequence of amino acids.

Amino Acids:

2. Making Sickle Cell Hemoglobin

In sickle cell anemia, there is a mutation at the seventeenth nucleotide of DNA in this gene; the nucleotide is changed from A to T. Fill in the complementary DNA strand, mRNA, and amino acid sequence in the hemoglobin protein.

DNA: GTG CAC CTG ACT CCT GTG GAG

DNA:

mRNA:

Amino Acids:

3. The Effect of Changing One Amino Acid

You can see that in normal hemoglobin, amino acid #6 is glutamic acid (Glu) and in sickle cell hemoglobin, amino acid #6 is valine (Val). Observe the two structural formulas for these amino acids:
Note: if these amino acid figures do not display correctly on your browser, please refer to your textbook or to the pdf downloadable version of this document.

H O | || óóNóóCóóCóó | | H CH2 | CH2 | C // \ O O- glutamic acid

H O | || óóNóóCóóCóó | | H CH // \ CH3 CH3       valine

Describe which amino acid is polar and which one is nonpolar. How can you tell which is which?

Although the altered b globin has only one amino acid changed out of the total of 146, itís a crucial amino acid. When this new amino acid is at position #6 instead of the correct amino acid, the overall hemoglobin b chain becomes more hydrophobic. As a result, when the hemoglobin chains fold into their 3-dimensional shape and assemble together, the resulting molecules tend to STICK TOGETHER, forming long chains of hemoglobin.

This altered hemoglobin deforms the normally rounded cell into the sickle shape. These red blood cells are destroyed at an increased rate, causing anemia. They are also prone to becoming stuck in capillaries, causing pain, organ damage, and often premature death.

Summary

1. How does sickle cell hemoglobin differ from normal hemoglobin at the primary level of protein structure (order of amino acids)?

 

2. How does sickle cell hemoglobin differ from normal hemoglobin at the fourth level of protein structure (the sum of all the folded protein chains)?

 

3. What is the effect on the red cell containing this altered hemoglobin?

 

Genetics review

Let A=allele for normal hemoglobin and S=allele for sickle hemoglobin.

1. What inheritance pattern does sickle cell anemia follow? (dominant, recessive, or other?)

 

2. What is Rosalynís genotype?

 

3. If Rosalyn has a child, what are the chances the child would have sickle cell anemia if the father was a sickle cell carrier? Show using a Punnett square.

Contributed by Jeanne Ting Chowning, BioLab, Seattle, WA
Provided jointly by the GENETICS Project and the Genetics Education Partnership http://genetics-education-partnership.mbt.washington.edu