Rearrangements of the beta-globin gene cluster in apparently typical beta(s) haplotypes

Background and Objectives. The majority of the chromosomes with the beta (S ) gene have one of the five common haplotypes, designated as Benin, Bantu, Senegal, Cameroon, and Arab-Indian haplotypes. However, 5-10% of the chromo somes have less cam mon haplotypes, usually referred to as atypical haploty pes. We have demonstrated that most atypical haplotypes are generated by re combinations. The present study was carried out in order to explore whether recombination also occurs in chromosomes with the common (or typical) hapl otypes. Design and Methods. We screened the HS-2 region of the beta -globin gene lo cus control region (LCR) in 244 sickle cell patients who had typical restri ction fragment length polymorphism (RFLP)-defined haplotypes of the beta (s )-gene cluster. Far 14 cases in which the expected and the observed LCR rep eat-sequence sizes were discrepant, the analysis was extended to other unex plored polymorphic markers of the Ps-globin gene cluster, i.e.: pre-(G)gamm a framework, pre-(G)gamma 6-bp deletion, HS-2 LCR (AT)xR(AT)y and pre- beta (AT)xTy repeats, and the intragenic beta -globin gene framework. Results. in all 14 cases (15 chromosomes) in which the LCR repeat-sequence sizes were discrepant, a recombination involving a typical 3' segment of th e beta (S) globin gene cluster was demonstrated. In most of the cases, the recombination site was located between the beta -globin gene and the beta L CR. Nine cases involving recombination were detected among 156 Brazilian Hb S homozygotes and five among 88 African patients homozygotes for the Benin haplotype. Interpretation and Conclusions, Thus, 3.1% of apparently typical haplotypes linked ta the sickle cell gene involve recombinations similar to those tha t generate the atypical haplotypes, a finding that reinforces the picture o f the beta -globin gene cluster as highly dynamic. (C) 2001, Ferrata Storti Foundation.