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

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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 βs 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 aγt 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 βs-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 βS chromosome were those commonly associated with the African origins of βS 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.