Mystery of the Crooked Cell


mystery-of-crooked-cellMystery of the Crooked Cell is an activity developed by MDBio Foundation to help students explore genetic diseases and tracing genetics through the use of Punnett squares and gel electrophoresis.

Sickle cell anemia is a hereditary disease that is passed down to an individual from their parents. The disease causes red blood cells to form into an abnormal crescent shape, which prevents the cells from efficiently carrying oxygen to the body’s tissues.

Learning Objectives

Upon completion of the Mystery of the Crooked Cell Lab, students will be able to:

  • Illustrate how amino acids interact to create a protein
  • Identify an enzyme’s specific substrate
  • Recognize the symptoms of sickle cell anemia and hemoglobin’s role in the disease
  • Differentiate between a patient with sickle cell anemia and a patient without sickle cell anemia using gel electrophoresis
  • Calculate the probability of an offspring having a specific phenotype using a Punnett square
  • Analyze a pedigree to track a gene through a family
  • Show how a point mutation can change the function of a protein

Background Information

The crescent, or sickle, shape is due to a mutation in the gene that codes for  a protein in red blood cells which binds to oxygen. The mutation codes for a specific amino acid that results in a mutated hemoglobin protein called valine, which is hydrophobic. This hydrophobia causes the sickle shape of the red blood cell.

Normal Hemoglobin: This phenotype occurs when an individual has two wild alleles (in this lab, we represent this genotype as NN).

Sickle Hemoglobin: This phenotype only occurs when an individual receives two mutated alleles (represented as SS).

Carrier: An individual who receives one normal and one sickle allele from their parents is a carrier for sickle cell anemia (genotype represented as NS). A carrier may go into “sickle cell crisis,” experiencing the symptoms of sickle cell under severe circumstances. However, a sickle cell carrier is also more resistant to the infectious disease malaria.

Pre-Laboratory Engagement

Pre-Lab Questions:

  • What causes sickle cell anemia and how is it passed through genetics?
  • What is the difference between being heterozygous for a gene and homozygous for a gene?
  • What is the difference between a genotype and a phenotype?

Click here for the Pre-lab Classroom Activity for a group activity investigating patient history, manipulating models of alleles, and gathering evidence to aid in discussion of sickle cell anemia.

Laboratory Activity

A local high school football player was rushed to the hospital after collapsing on the field. The player reported to the emergency room physician, Dr. James Herrick, that he had experienced similar symptoms multiple times during his childhood. These symptoms include extreme fatigue after non-strenuous exercise, being unusually short of breath, extreme pain in his joints and muscles, a yellowish tint in the whites of his eyes, and tenderness in his abdomen. Consequently, the patient would often have to spend time in bed after a “crisis”.

A look at his immediate family history reveals that neither of his parents have had similar symptoms. However, upon further investigation, it is revealed that the patient’s paternal uncle and grandmother shared the same symptoms under the same circumstances. Based on this medical history, Dr. Herrick believes the patient may have sickle cell anemia.

Dr. Herrick has asked for your help in confirming his diagnosis. To do so, you will be testing the patient’s hemoglobin protein using gel electrophoresis. Based on your results, you can then confirm the patient’s diagnosis.

Post-Laboratory Extension

Click here to see our Post-Lab Classroom Activity, with discussion prompts and real-world applications to the sickle cell lab.

Specifications

  • Skill Level: Intermediate
  • Focus: Genetics, human diseases, cell biology, physiology
  • Time: 50 – 60 minutes

Student Handout

NGSS Alignment

HS-LS-1 From Molecules to Organisms: Structures and Processes

HS-LS-3 Genetics: Inheritance and Variation of Traits

Key Words

Hemoglobin, gel, electrophoresis, symptoms, patient, agarose, sickle, family, disease, protein, genotype, phenotype, Punnett square, point mutation, homozygous, heterozygous, dominant, recessive, pedigree

Additional Resources

For useful information regarding this lab, follow these links:

Other useful links:

What is a gene?

Proteins are the Body’s Workers
Look into amino acids, the building blocks of proteins

Sickle Cell Explained
Explanation of sickle cell disease

Center for Disease Control
One stop shop for information from the CDC on Sickle Cell Disease

CDC Resource for family history

A Brief History of Hemoglobin
Look into amino acids, the building blocks of proteins

Inheriting Genetic Conditions
Frequently asked questions on how diseases can travel through families

Point Mutations
NIH definition of point mutations

Quickgrabs

DNA Learning Center
3-D animation of the sickle cell mutation

Gel Electrophoresis Tools
Run a virtual gel electrophoresis

Hemglobin
3-D Model’s of the hemoglobin protein with options to show specific features of each side chain