Types of Sickle Cell Disease~
~An Introduction to the Genetics of Sickle Cell~
Author: Kara Martina, Biopsychology B. Sc.
Sickle Cell Disease is comprised of four main types. All are determined by our genetic code. Hemoglobin is the protein inside our red blood cells’ solution that carries oxygen and allows us to breathe, use energy and live our lives. The structure of this protein determines whether or not an individual has Sickle Cell complications…..
Which chromosomes code for hemoglobin?
Two chromosomes code for the four part structure of hemoglobin: 11 and 16. But over fifteen chromosomes work together to create your blood’s phenotype, as outlined by the HUGO Gene Nomenclature Committee in their list of genes in the blood group family. Although many genes change the type of blood you carry, the hemoglobin inside red blood cells is only modified by chromosome 11 and 16 which create the beta (ß) and alpha (α) subunits…
Which chromosome is responsible for Sickle Cell disease?
Chromosome 11, responsible for coding the beta chain (1). Genetic mutations in hemoglobin’s beta chain give rise to the disorders we classify under Sickle Cell Disease. According to the US National Library of Medicine, this mutation results in the production of an abnormal version of beta-globin called hemoglobin S or HbS. Hemoglobin S then changes both ß-chains in hemoglobin. The mutation changes a single amino acid in beta-globin. More specifically, the amino acid glutamic acid is replaced with the amino acid valine at position 6 in beta-globin.
Is Hemoglobin S the only mutation that causes Sickle Cell complications?
No. Full fledged, typical ‘Sickle Cell Anemia’ is indeed the result of two inherited HbS mutations on chromosome 11, one from the father and one from the mother. But this condition is only ONE type of Sickle Cell Disease. This homozygous state is short-handed HbSS or SS. Usually the most severe form of the disease, this SS genotype expresses Sickle Cell hemoglobin 100% of the time.
What other types are there?
Someone can inherit the HbS mutation form one parent but not from the other. These heterozygous people express less sickle hemoglobin, but the complications can still be as severe depending on the other gene they inherited. From the other parent, an individual can inherit:
An abnormal hemoglobin called “C”. In this case, the amino acid lysine has replaced glutamic acid at position 6. This produces unstable hemoglobin that forms crystals in the blood cells, eventually leading to an increase in the viscosity of the blood. The spleen effectively removes these crystal-containing cells and the result is usually a milder form of SCD.
Beta thalassemia (β0 and β+ ):
Beta thalassemia gene codes for another type of anemia where the entire production of the ß-globin chain is either hindered or completely stopped. Within this anemia an individual can be β0 or β+ .Those with HbS/β0 usually have a severe form of SCD while those with HbS/β+ tend to have a milder form.
Abnormal type of hemoglobin (“D”, “E”, or “O”):
There are over 350 hemoglobin abnormalities that can be inherited in combination with the HbS trait but the most common include HbD, HbE and HbO (2). By themselves, these genetic variants aren't lethal. They result in different types of anemia, HbO causing a similar anemia to HbC. But their combination in sync with the sickle trait escalates the severity, as is the case with HbD and HbO, abnormalities found in populations of North India and East Africa respectively. The Hb E, found mostly in South East Asian populations, is the most common variant and again is another form of mild anemia on its own, but once inherited with the sickle trait results in greater complications.
Normal gene (“A”) HbAS:
The normal gene codes for a healthy beta-chain in the hemoglobin molecule! Individuals with the HbAS combination have the sickle cell trait (SCT) and usually do not have any signs of the disease and live a normal life. They can obviously pass the trait on to their children and may experience some uncommon health problems that might be linked to the trait.
How can genetic research help those with SCD?
According to the National Institute of Health, new research efforts include studies of:
· Genetic factors affecting sickle cell disease symptoms
· Regulation of hemoglobin production
· Development of drugs to increase fetal hemoglobin production
· Gene therapy
Science Daily made claim of a gene regulator that targeted hemoglobin production, which in turn could be used to manipulate its production (3). This discovery, back in 2013, may be the beginning of new insights into the mechanisms of the Sickle Cell. Being a genetic disease whose symptoms and complication can only be treated, chromosome 11 is looking like a promising place to start for a Sickle Cell cure….
1 King M. (2014). Hemoglobin. Retrieved from themedicalbiochemistrypage.org/hemoglobin-myoglobin.php
2 Centers for Disease and Control Prevention. (2014). Sickle Cell Disease (SCD). Retrieved from www.cdc.gov/ncbddd/sicklecell/facts.html
3 Dana-Farber Cancer Institute. (2013, October 10). Newly discovered gene regulator could precisely target sickle cell disease. ScienceDaily. Retrieved June 20, 2014 from www.sciencedaily.com/releases/2013/10/131010142752.htm