SCA _ 1111

SCA & The Mitochondrion

The Inheritance Pattern of SCA

SCA & Meiosis

Sickle Cell Anemia

Info

Info

Info

SCD Symptoms & Treatments

The Genetics Behind SCA

SCA Statistics

Mice & SCA

Dr. KT Lemon

Info

Info

Sickle Cell Anemia (SCA)

• Sickle cell anemia is an autosomal recessive disorder.

• People who have SCA have abnormal hemoglobin, a protein that carries oxygen.

• The abnormal protein is produced because of mutations in the HBB gene.

Hemoglobin is shown above. It has four subunits, two alpha chains and two beta chains. The HBB gene makes the beta chains of hemoglobin.

The Genetics Behind SCA

• The HBB gene is located on chromosome 11 (11p15.4).

• A single nucleotide change in the HBB gene causes the production of valine (a hydrophobic amino acid), thereby changing the function of the hemoglobin Beta protein.

• The original DNA sequence was GAG, but the mutation changes it to GTG.

Effects of the Mutation

• The red blood cells (RBCs) become sickled and tend to stick together.
• The sickled cells block blood flow and die early, leading to anemia.

• Common symptoms experienced by people with SCA include shortness of breath, delayed growth and development, fatigue, jaundice, and painful swelling in the hands and feet.

The Genotypes of SCA

SCA is the only condition we will discuss that utilizes two different letters to represent the genotype.

• A = represents normal hemoglobin
• S = represents abnormal hemoglobin

A blood test can diagnose SCA as shown above.

The Inheritance Pattern of SCA

• SCA is inherited in an autosomal recessive pattern
• Two bad copies of the HBB gene are needed for an individual to develop SCA.
• Individuals with hemoglobin S and A are considered carriers of the SCA trait.

Pedigree Details

• I-1 is a male who is a carrier. His genotype is AS.
• I-2 is a female who is a carrier. Her genotype is AS.
• They have three children, II-2 (female with SCA; genotype SS), II-3 (male carrier; genotype AS), and II-4 (normal female; genotype- AA).
• II-2 is married to II-1 (normal male; genotype AA).
• They have one child, III-1 (carrier male; genotype AS).

Pedigree of SCA

NOTE- SCA is the only condition we will discuss that utilizes two different letters to represent genotype.

SCA & Meiosis

• SCA is a genetic disorder that is inherited through meiosis.

• This is because meiosis is the process of cell division that creates gametes.

• The diagram to the right depicts the two gametes produced during meiosis and the process of creating a diploid organism.

SCA & Meiosis continued

• The pedigree shown can be used to showcase how SCA is associated with meiosis.
• I-1 produced the sperm cell partially responsible for producing II-2. That sperm cell carried one mutated copy of the HBB gene.

• I-2 produced the egg cell partially responsible for producing II-2. It too carried one mutated copy of the HBB gene.

• The result of the two sex cells uniting was a girl who had sickle cell anemia, II-2.

Pedigree of SCA

SCA & Mitochondria

Mitochondria are specialized organelles responsible for cellular energy production.

Normally, mitochondria are lost when RBCs mature.

In patients who have SCA, mature RBCs maintain their mitochondria (the red structures).

A 3D rendering of mitochondria (red) inside a sickled RBC

SCA & the Model Mouse

• Researchers have created a transgenic mouse model of sickle cell using Mus musculus (common name- house mouse) to detail the pathophysiology of the disease and to assist in the development of treatment options for SCA.
• A transgenic organism carries a foreign gene that has been deliberately inserted into its genome. The foreign gene is constructed using recombinant DNA methodology.

The diagrams above explain why mice are a good choice for SCA research.

SCA Quiz

Now that you completed the interactive infographic, navigate to the quiz on GAVIEW.