β-Globin Gene Cluster Haplotypes in Iranian Patients with β-Thalassemia

Introduction: β-globin gene cluster haplotypes are useful in diagnosis of particular molecular defects in β-thalassemia, prenatal diagnosis of β-thalassemia, and elucidating population affinities. Methods: β-globin gene cluster haplotypes were studied in 150 β-thalassemia minor and 52 healthy in-dividuals from the Fars province of Iran. DNA was extracted from leukocytes of whole blood by phe-nol-chloroform. Haplotype was determined by PCR-RFLP technique. Results: There were 26 out of 150 with homozygous haplotypes. Haplotype I was found as the most prevalent haplotype among both patients and normal individuals. Out of 26 patients bearing homozy-gous haplotypes, 12 (46.2%) had typical haplotype I and 3 (11.5%) had atypical haplotype I. The prevalence of haplotype I in normal control subjects was around 43% (45 out of 104 βA chromo-somes). The second prevalent haplotype was haplotypes V (15.4%) and III (15.4%) for homozygous patients and controls, respectively. The most frequent mutation in patients was IVS II.1 (G→A) that was not linked to a single haplotype. IVS I.110 (G→A) mutation was linked to haplotype I. Mutation in codon 30 (G→A) was associated with haplotype V. Conclusion: Being Haplotype I the most prevalent haplotype in β-thal and βA chromosomes, implies that β-thalassemia mutations might have arisen in the chromosomal background common in the popula-tion, rather than due to selection pressure or gene flow (migration). Patients with haplotype IX had the highest HbF levels compared to other haplotypes.