β-Cluster Haplotypes, α-Gene Status, and Hematological Data from SS, SC, and S-β-Thalassemia Patients in Southern California

Abstract

The β-gene-cluster haplotype and α-gene status were determined for 221 patients with sickle cell anemia, 41 with SC disease, and 21 with S-β-thalassemia.

Among SS patients, eleven β^s haplotypes were found in 21 combinations. Three haplotypes — the Benin (Ben) [—+−], the Central African Republic (CAR) [+—−+], and the Senegal (Sen) [+−+++] —comprise 61%, 21%, and 10% of the chromosomes, respectively. Cleavage at the Xmn I sie 5′ to the ^Gγ gene was observed only when the Senegalese arrangement was present. The linear correlation which exists between the absolute value of the Gy chains and the Hb F for each haplotype combination suggests a feed-back mechanism which controls the ^Gγ to ^Aγ ratio and thus the Hb F level (or vice versa). The ^aγ^t chain was present with specific haplotypes [++−++] and [++−+−].

Heterozygous or homozygous α-thalassemia-2 was present in 36% of the SS patients and was randomly distributed among β^s-gene-cluster haplotypes.

The variable levels of hemoglobin, MCV, Hb F, ^Gγ chains, and Hb A2 are in response to the heterogeneous genetic mix of the βs-gene-cluster haplotypes and α-thalassemia-2 in American patients with sickle cell anemia. The influence of α-thalassemia-2 on the level of Hb F is dependent on the βs-cluster haplotype. Hb A₂ levels increased with decrease in the number of a genes.

Among SC and S-B-thalassemia patients the β-cluster polymorphisms on the β^S chromosome were those commonly associated with the African origins of β^S haplotype. The haplotype [+−-+−] was present on the C chromosome in 90% of the cases. Most β-thalassemia chromosomes had haplotypes that matched the common African polymorphisms. An a-gene deletion was found in 29% of the SC and S-β-thalassemia patients.