β-Globin Gene Cluster Haplotype Analysis as a Predictor of Sickle Cell Disease Severity

Abstract

The origin of sickle cell disease has been traced to Africa and is due to a genetic mutation in the βglobin gene. Factors contributing to the variance in disease severity include levels of fetal hemoglobin, the presence of α-thalassemia, and the type of hemoglobin haplotype linked to the βglobin gene complex. Five different haplotypes (haplotypes 19, 20, 17, 3, 31) have been identified. Patients with haplotypes 3 and 31 have the highest levels of fetal hemoglobin and mild disease presentation. Patients with haplotype 20 have the lowest levels of fetal hemoglobin and the most severe disease presentation. Patients with haplotype 19 and 17 have intermediate levels of fetal hemoglobin and moderate disease severity. The relative amounts of G γ, A γ chains in patients with haplotypes 3 and 31 are different from those of haplotypes 19, 20, and 17. Knowledge of the β-globin gene cluster haplotypes may serve as markers for predicting disease severity.