The HBB gene has been the subject of immense research because of the severe diseases that results from its mutations, most notably among them being the inherited blood disorder sickle cell anemia, a common form of sickle cell disease, and the sickle cell trait. I will begin from a broad standpoint, discussing the evolutionary importance of the sickle cell trait as a protective measure against the often-lethal disease malaria. Then, the I will explore the molecular and biological details surrounding the sickle cell mutation, ranging from why the sickle cell trait is considered milder compared to sickle cell disease, how exactly the sickle cell trait confers resistance against malaria, why infants have a greater resistance to the disease compared to adults, and finally, the specific missense mutation that results in the disease itself.
Before going further, the terminology distinction between sickle cell trait and sickle cell disease should be explained. The sickle cell trait occurs if a person inherits both the gene for hemoglobin S, the abnormal allele of the HBB gene, and the gene for hemoglobin A, the unaffected allele of the HBB gene—in other words, the sickle cell trait occurs if the offspring is heterozygous, or a carrier, for sickle cell disease. Conversely, sickle cell anemia, a form of sickle cell disease,describes the condition where the offspring is homozygous, inheriting a mutated copy of the sickle-cell gene from both parents. While sickle cell disease may provide higher resistance against malaria than the sickle cell trait, it is highly damaging on its own, and can prove to be fatal. Sickle cell trait, by contrast, is milder—the reason for which will be explained in sec. II—and provides an effective compromise between its own deleterious effects and the resistance it confers against malaria.
The mutated form of normal hemoglobin tends to stick to other hemoglobin molecules within a red blood cell, forming sickle-shaped strands and, thus, a sickle cell—the reason for which will be discussed in sec. V as well. Compared to normal red blood cells, sickle cells die far more quickly and are unable to be replaced quick enough. Consequently, anemia can develop to the severe deficiency of red blood cells. Additionally, it is difficult for sickle cells to fit through small blood vessels. As a result, blockages within the blood vessels can form, and oxygenated blood may be unable to reach tissues and organs. In addition to severe pain, affected people may suffer from damaged tissues and organs, which could lead to more dangerous complications such as stroke and an impaired immune system. Other complications could include an enlarged spleens and infections, delayed growth, acute chest syndrome, and painful crises.
“Sickle Cell Disease | Sickle Cell Anemia.” MedlinePlus, U.S. National Library of Medicine, 30 June 2021, https://medlineplus.gov/sicklecelldisease.html.
“Sickle Cell Disease.” National Heart Lung and Blood Institute, U.S. Department of Health and Human Services, https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease.
William C. Shiel Jr., MD. “21 Sickle Cell Anemia Symptoms, Treatment, Life Expectancy, Genetics.” MedicineNet, MedicineNet, 22 June 2021, https://www.medicinenet.com/sickle_cell/article.htm.