Contributed by Ziad Jowhar, Elie Nwefo, Yasmine Alkhalid, Sai Greeshma Magam, Rasika Tangutoori, & Shray Ambe
Imagine waking up everyday with fatigue and joint pain. You constantly fear having a stroke or heart attack that could cause your premature death. Unfortunately, this is a reality for patients dealing with severe forms of sickle cell disease (SCD).
SCD is caused by a recessive mutation on chromosome eleven and primarily affects the cardiovascular system. Red blood cells are essential for transporting oxygen to the rest of your body. These cells are normally round, allowing them to fit through small blood vessels. Individuals with SCD, who are homozygous for the sickle cell allele, have red blood cells that are crest-shaped instead. This deformity can cause blood clots, ultimately leading to tissues in the body to become oxygen deprived. If this blockage occurs in a major vessel, it can cause a stroke, heart attack, or even death. However, there is hope for individuals with the disease, as recent research has found that SCD can be cured through bone marrow transplant. Sadly though, there are limitations — it has been more successful in younger patients who receive transplants from a full sibling or matched donor.
But how can such a harmful disease manage to survive? One misconception is that the fittest organisms in a population are the healthiest. Shouldn’t the sickle cell trait have been erased from the human population long ago since it lowers life expectancy?
Before we dive into why the sickle cell trait still exists, let’s take a step back and learn a little more about SCD’s effects and treatment options from Dr. Kirshma Khemani, a specialist in pediatric hematology and oncology:
- Could you give a brief background on yourself and your current research?
- What are the symptoms of sickle cell disease?
- What are the current treatment options for sickle cell disease?
- What are the risks of each treatment option for sickle cell disease?
- Recently stem cell therapy has been identified as a potential cure for sickle cell disease, what are your views on these findings?
Now, let’s get back to the big question: how could this trait continue to prevail? The sickle cell trait has been found in regions of the world where malaria occurs: 10-40% of the population carries the sickle cell mutation. But wait a second. What is malaria and how is it related to SCD?
Malaria is a life threatening disease that is caused by a parasite and is transmitted through mosquito bites. There is a correlation between malaria and SCD: individuals who carry the sickle cell trait, who are heterozygous for the sickle cell allele, have a protective advantage against malaria. This occurs because the parasite that causes malaria cannot mature in the oxygen-deprived sickled red blood cells and dies.
Although SCD does have several disadvantages, the sickle cell trait has been able to survive in the population due to its protective role against malaria.
For additional information, see the following references:
Gemmell NJ, Slate J. 2006. Heterozygote advantage for fecundity. PLoS ONE 1(1).
Kwiatkowski, D. P. 2005. How malaria has affected the human genome and what human genetics can teach us about malaria. The American Journal of Human Genetics, 77(2), 171-192.
Larremore, D. B. et al. 2015. Ape parasite origins of human malaria virulence genes. Nature Communications Nat Comms, 6.
Saraf, S. L. et al. 2015. Nonmyeloablative stem cell transplantation with alemtuzumab/low-dose irradiation to cure and improve the quality of life of adults with sickle cell disease. Biology of Blood and Marrow Transplantation.
Sellis, D., Callahan, B. J., Petrov, D. A., & Messer, P. W. 2011. Heterozygote advantage as a natural consequence of adaptation in diploids. Proceedings of the National Academy of Sciences, 108(51), 20666-20671.
Williams, T. N. et al. 2005. An immune basis for malaria protection by the sickle cell trait. PLoS Med PLoS Medicine 2: 441-445.