Abstract

Background: A variety of mutations influencing gene transcription, translation, or mRNA processing have been identified in β-thalassemia. Several studies demonstrated a nonrandom linkage of particular RFLP haplotypes with specific β-thalassemia mutations. Linkage analysis using β-globin haplotypes is a valuable tool for indirect mutation detection. Our aim was to determine the spectrum and frequency of β-thalassemia mutations among Northwestern Iranians (Azeri Turkish population) along with determining the heterozygosity and polymorphism information content (PIC) value for seven β-globin markers. Method: We investigated spectrum of β-thalassemia mutations via ARMS-PCR technique followed by sequencing technique. Also β-globin gene cluster haplotypes was determined by PCR-RFLP technique on DNA samples of the patients and his (her) parents or siblings. Result: We detected 36 different mutations among 554 non-identical mutant chromosomes. The most frequent mutation was IVSII-1 (G>A) (23.6%), followed by IVSI-110 (G>A) (11.9%) and CD8 (-AA) (10.5%). Of the various β- globin gene cluster haplotypes, haplotypes I and IV were found to be most common among normal (21.36%) and mutant (15.76%) chromosomes, respectively. The highest observed heterozygosity (48%) was found for the HindIII Gγ and HindII 5'ψß polymorphic sites, whereas the highest expected heterozygosity (50%) was predicted for the HindIII Gγ and HindII sites, which also had the highest PIC value of 0.37. Conclusion: The current study implies mutational heterogeneity among investigated population. Haplotype study results (heterozygosity and PIC), clarifies β-globin markers usefulness for tracking mutant alleles as a complementary method to confirm the genotype in prenatal diagnosis (PND) among investigated population.

Keywords: β-thalassemia; Haplotypes; DNA polymorphism; Prenatal diagnosis