title: Beta-cluster haplotypes, alpha-gene status, and hematological data from SS, SC, and S-beta-thalassemia patients in southern California.
abstract: The beta-gene-cluster haplotype and alpha-gene status were determined for 221 patients with sickle cell anemia, 41 with SC disease, and 21 with S-beta-thalassemia. Among SS patients, eleven beta 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 site 5' to the G gamma gene was observed only when the Senegalese arrangement was present. The linear correlation which exists between the absolute value of the G gamma chains and the Hb F for each haplotype combination suggests a feed-back mechanism which controls the G gamma to A gamma ratio and thus the Hb F level (or vice versa). The A gamma T chain was present with specific haplotypes [++-++] and [++-+-]. Heterozygous or homozygous alpha-thalassemia-2 was present in 36% of the SS patients and was randomly distributed among beta S-gene-cluster haplotypes. The variable levels of hemoglobin, MCV, Hb F, G gamma chains, and Hb A2 are in response to the heterogeneous genetic mix of the beta S-gene-cluster haplotypes and alpha-thalassemia-2 in American patients with sickle cell anemia. The influence of alpha-thalassemia-2 on the level of Hb F is dependent on the beta S-cluster haplotype. Hb A2 levels increased with decrease in the number of alpha genes. Among SC and S-beta-thalassemia patients the beta-cluster polymorphisms on the beta S chromosome were those commonly associated with the African origins of beta S haplotype. The haplotype [+--+-] was present on the C chromosome in 90% of the cases. Most beta-thalassemia chromosomes had haplotypes that matched the common African polymorphisms. An alpha-gene deletion was found in 29% of the SC and S-beta-thalassemia patients.
authors: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.
authors: W A
authors: WA
authors: Schroeder
authors: D R
authors: DR
authors: Powars
authors: L M
authors: LM
authors: Kay
authors: L S
authors: LS
authors: Chan
authors: V
authors: V
authors: Huynh
authors: J B
authors: JB
authors: Shelton
authors: J R
authors: JR
authors: Shelton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics*; D002140:California; D002648:Child; D002675:Child, Preschool; D015245:Deoxyribonuclease BamHI; D015246:Deoxyribonuclease EcoRI; D015252:Deoxyribonucleases, Type II Site-Specific; D005319:Fetal Hemoglobin / Q000032:analysis; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006443:Hemoglobin A2 / Q000032:analysis; D006450:Hemoglobin SC Disease / Q000097:blood / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D013789:Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D005914:Globins; D006443:Hemoglobin A2; D005319:Fetal Hemoglobin; D015245:Deoxyribonuclease BamHI; D015246:Deoxyribonuclease EcoRI; C028649:endodeoxyribonuclease XmnI; D015252:Deoxyribonucleases, Type II Site-Specific