Schroeder W A, Powars D R, Kay L M, Chan L S, Huynh V, Shelton J B, Shelton J R
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.
Hemoglobin. 1989;13(4):325-53. doi: 10.3109/03630268909003397.
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.
对221例镰状细胞贫血患者、41例SC病患者和21例S-β地中海贫血患者进行了β基因簇单倍型和α基因状态的检测。在SS患者中，发现了11种βS单倍型，存在21种组合。三种单倍型——贝宁型（Ben）[---+-]、中非共和国型（CAR）[+---+]和塞内加尔型（Sen）[+-]——分别占染色体的61%、21%和10%。仅当存在塞内加尔排列时，才观察到在Gγ基因5'端的Xmn I位点处的切割。每种单倍型组合的Gγ链绝对值与Hb F之间存在的线性相关性表明存在一种反馈机制，该机制控制Gγ与Aγ的比例，从而控制Hb F水平（反之亦然）。AγT链与特定单倍型[++-++]和[++-+-]同时存在。36%的SS患者存在杂合或纯合α地中海贫血-2，且随机分布于βS基因簇单倍型之间。美国镰状细胞贫血患者血红蛋白、平均红细胞体积、Hb F、Gγ链和Hb A2的水平各异，这是对βS基因簇单倍型和α地中海贫血-2的异质基因组合的反应。α地中海贫血-2对Hb F水平的影响取决于βS簇单倍型。Hb A2水平随着α基因数量的减少而升高。在SC和S-β地中海贫血患者中，βS染色体上的β簇多态性是那些通常与βS单倍型的非洲起源相关的多态性。在90%的病例中，C染色体上存在单倍型[+--+-]。大多数β地中海贫血染色体的单倍型与常见的非洲多态性相匹配。在29%的SC和S-β地中海贫血患者中发现了α基因缺失。
