Inheritance of Sickle Cell
Sickle cell is an inherited disease. Thus, a person who has sickle cell is born with it. Learning more about inheritance can help you understand how sickle cell and sickle cell trait are passed from parents to a child.
How Is Sickle Cell Inherited?
Genes usually come in pairs: one copy of a gene comes from each biological parent. This pair of genes is known as a genotype. Sickle cell disease is caused by inheriting two copies (one from each parent) of an altered HBB gene, which causes the production of an abnormal form of beta (β)-globin, such as hemoglobin S (HbS). Scientists have identified hundreds of variations in the HBB gene that cause abnormal beta-globin to form and cause disease. As a result, there is more than one type of sickle cell, which depends on the specific combination of alterations of the HBB gene you inherit. These different forms are described as your sickle cell genotype.
Determining Inheritance Tool
Use the interactive diagram below, called a Punnett square, to see the likelihood of a child inheriting a form of sickle cell disease or sickle cell trait. This Punnett square can help you see how genes can be passed from a parent to a child in every single pregnancy, regardless of the genotypes of previous children. Note that the “sickle cell disease” selection for this tool is for the most common type of sickle cell, hemoglobin SS. However, you can create your own Punnett square by following the format below and using a different genotype (such as hemoglobin SC or hemoglobin S beta-zero) in place of “SS”.
Select a genotype (ie, AA, no sickle cell disease; AS, sickle cell trait carrier; or SS, sickle cell disease) for both the male and female, then select “View Results” to see the chances of a child inheriting sickle cell trait or sickle cell disease.
Normal HBB gene
Sickle HBB gene
Types of Sickle Cell
As previously mentioned, there are hundreds of variations in the HBB gene that can cause abnormal beta-globin to form, and a genotype describes the alteration of the HBB gene that a person inherits from their parents. In other words, the genotype describes the type of sickle cell.
The most common alteration in the HBB gene leads to the SS genotype. Other types of sickle cell are a result of inheriting one hemoglobin S gene and one different abnormal beta-globin gene. For example, inheriting one hemoglobin S gene and one hemoglobin C gene would result in an HbSC genotype. Some sickle cell genotypes are more common than others, with the severity of symptoms and complications varying across these different types.
| TYPES OF SICKLE CELL | ||
|---|---|---|
| Genotype | Genotype Breakdown | |
| Most common | ||
| Hemoglobin SS | Inheriting two HbS genes | |
| Hemoglobin SC | Inheriting one HbS gene and one HbC gene | |
| Hemoglobin Sβ+ (beta) thalassemia | Inheriting one HbS gene and one Hb beta-thalassemia gene | |
| Hemoglobin Sβ0 (beta zero) thalassemia | Inheriting one HbS gene and one Hb beta zero thalassemia gene | |
| Less common | ||
| Hemoglobin SD | Inheriting one HbS gene and one HbD gene | |
| Hemoglobin SE | Inheriting one HbS gene and one HbE gene | |
| Hemoglobin SO | Inheriting one HbS gene and one HbO gene | |
Sickle Cell Trait
A person who carries the sickle cell trait inherits one copy of an abnormal (sickle) HBB gene and one copy of a normal HBB gene. This means that although their red blood cells contain some HbA, a portion of their red blood cells (20%-45%) consists of HbS. The levels of HbS in people with sickle cell trait are largely genetically determined. At rest, their red blood cells appear healthy—smooth and disc-shaped. However, under certain circumstances, their red blood cells can appear sickle shaped, and trait carriers can experience some of the symptoms of sickle cell. Conditions such as high altitudes, severe dehydration, and low oxygen can lead to complications including:
- Reduced blood supply to the spleen
- Muscle breakdown (rhabdomyolysis)
- Kidney damage and chronic kidney disease
- Bleeding (hyphema) and increased pressure in the eye (glaucoma) following eye injuries
- Sudden death with extreme exertion
- Kidney cancer (renal medullary carcinoma), exceedingly rare
Because a person who carries the sickle cell trait may not experience symptoms, they may be unaware that they are a carrier. However, they are still able to pass the abnormal (sickle) HBB gene along to their children. A simple blood test from your doctor can determine if you are a carrier and at risk of passing along the abnormal gene.