Investigation of RFLP Haplotypes β- Globin Gene Cluster in Beta-Thalassemia Patients in Central Iran

Abstract

Introduction: Beta-thalassemia is one of the most prevalent inherited blood diseases among Iranians. The aim of this study was to elucidate the chromosomal background of beta-thalassemia mutations in Esfahan province, Iran.
 Materials and Methods: In this study, we investigated three frequent mutations (c.315+1G>A, c.93-21G>A and c.92+5G>C in β-globin gene, the frequency of RFLP haplotypes, and LD between markers at β-globin gene cluster) in 150 beta-thalassemia patients and 50 healthy individuals. The molecular and population genetic investigations were performed on RFLP markers HindIII in the c.315+1G>A of Gγ (HindIIIG) and Aγ (HindIIIA) genes, AvaII in the c.315+1G>A of β-globin gene and BamHI 3' to the β-globin gene. All statistical analyses were performed using Power Marker software and SISA server.
 Results: Fifty percent of beta-thalasemia patients were associated with these mutations. Haplotype I was the most prevalent haplotype among beta-thalassemia patients (39.33%) and normal individuals (46%). The commonest c.315+1G>A mutation in our population was tightly linked with haplotype III (43.75%) and haplotype I (31.25%). The second prevalent mutation, c.92+5G>C, was 90%, 6.66%, and 3.33% in linkage disequilibrium with haplotypes I, VII, and III, respectively. The c.93-21G>A mutation indicated a strong association with haplotype I (80%).
 Conclusion: Our study participants like beta-thalassemia patients from Kermanshah province was found to possess a similar haplotype background for common mutations. The emergence of most prevalent mutations on chromosomes with different haplotypes can be explained by gene conversion and recombination. High linkage of a mutation with specific haplotype is consistent with the hypothesis that chromosomes carrying beta-thalassemia mutations experienced positive selection pressure, probably because of the protection against malaria experienced by beta-thalassemia carriers.

Prevalence of RDB, RSa, Hinc and Xmn polymorphisms and HBBS11D haplotypes in patients with thalassemia minor

“…The results showed that 50% of betathalassemia patients were associated with these mutations. The most common haplotype of this study was observed in 39.33% of patients and 46% of normal individuals [25]. It was identified [26] that 20 different mutations in the beta-globin gene associated with beta-thalassemia disease.…”

“…It was related [25] that 150 patients with beta-thalassemia and 50 healthy individuals with RFLP polymorphisms were studied. Also, three abundant mutations named c.315G> A, c.93-21G> A, and c.92 + 5G> C were examined.…”

To Study the β-Globin Haplotype Pattern of Descent of a Set of Linked Alleles Occurring on the Same Chromosome in the Northern Province of India

“…The samples were screened by five restriction enzymes via restriction fragment length polymorphism (RFLP): Hinc II, Hind III, Hinf I, Ava II, and BamHI [20]. The β-globin gene cluster and the location of the different restriction sites used in the study are shown in Figure 1 [21]. The targeted restriction sites were amplified through polymerase chain reaction (PCR) using mutation-specific primers and procedures [22][23][24].…”