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

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.