Inheritance of Sickle Cell

Sickle Cell

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.

How is Sickle Cell Inherited?

Genes usually come in pairs: one copy of a gene comes from a female parent and one copy from a male parent your mother, and one copy comes from your father. This set of genes is known as a genotype. Sickle cell disease is caused by inheriting two copies (one from each parent) of an altered (mutated) HBB gene, which causes the production of an abnormal form of beta (β)-globin, hemoglobin S (HbS).

Abnormal (sickle) HBB gene a gene mutation that produces hemoglobin S, which causes red blood cells to sickle

Normal HBB gene Gene that provides cells with instructions for making a protein called β‑globin (beta-globin)

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.

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.