What is the genetic basis of sickle-cell disease?

Sickle-cell disease is an autosomal recessive disorder, which means that an individual must inherit two copies of the mutated gene—one from each parent—to express the disease. The disorder is primarily caused by a mutation in the hemoglobin-beta gene (HBB) located on chromosome 11. This mutation leads to the production of abnormal hemoglobin known as hemoglobin S, which causes red blood cells to assume a rigid, sickle shape under low-oxygen conditions.

In individuals with sickle-cell disease, the sickle-shaped cells can block blood flow and break down prematurely, leading to various health complications such as pain episodes, anemia, and increased risk of infections. Since it is a recessive disorder, individuals with only one copy of the mutated gene (heterozygotes) are typically asymptomatic and are referred to as carriers or have sickle-cell trait, which highlights the importance of inheriting two defective copies to develop the disease.

This genetic inheritance pattern distinguishes sickle-cell disease from other options such as X-linked disorders, which primarily affect males and are tied to genes on the X chromosome, or autosomal dominant disorders, where only one copy of the mutated gene is sufficient to cause the disease. Mitochondrial disorders