Detection of −α 3.7 and _ _SEA deletions in α-globin gene in the Bangladeshi population

Abstract

Abstract Background: α-thalassemia, resulting largely from deletions in the α-globin chain of hemoglobin, is one of the most common inherited blood disorders among the Asian population. The α-globin gene locus (HBA1 and HBA2), located on chromosome 16p13.3, includes two highly homologous genes that produce identical α-globin protein products after translation. The most common single α-gene deletions are −α3.7 , −α4.2, – –SEA, – –FIL, – –THAI, – –MED and – –(α)20.5). Patients with α-thalassemic mutations often suffer from severe anemic conditions. In Bangladesh, the prevalence of α-thalassemia, mutation spectrum, and carrier frequency are unknown. This study aimed to detect the carrier frequency of the two most frequent α-gene mutations namely -α3.7 deletion and _ _SEA deletion in the α-globin gene in the Bangladeshi population. Methods: Blood samples from 1824 participants were randomly collected from different educational institutions in Bangladesh. Complete Blood Counts (CBC) and Hemoglobin electrophoresis were performed for MCH (Mean Corpuscular Hemoglobin), MCV (Mean Corpuscular volume), and HbA2 analysis to initially screen individuals with abnormal α-globin chains. For molecular analysis, genomic DNA extraction followed by conventional gap-PCR to detect -α3.7 deletion and real-time PCR-based melting-curve analysis to identify _ _SEA deletion were conducted. Sanger sequencing was performed for the detection of Single Nucleotide Polymorphisms (SNP) within the α-globin gene. Results: 63 participants with decreased levels of MCH, MCV, and HbA2% were identified as suspected to have α-globin mutation. Among the suspected group, silent carrier status of -α3.7 deletion (αα/-α3.7) was found in 17.5% (11/63) samples, while 1 participant had trait genotype (-α3.7/-α3.7 or --/αα) and one individual had the triplicated genotype (αα/αααanti 3.7). A total of 37 healthy participants without any abnormal hematological parameters were also included in the deletion analysis. In 37 healthy samples, the deletion frequency was 8.1% (3/37) for (αα/-α3.7) deletion, 2.7% (1/37) for the trait, and 2.7% (1/37) for the triplicated genotype. The _ _SEA deletion was not found in any sample, but SNP rs2541677(G>A) was detected within the region. For (rs2541677 (G>A) of α-globin, 91% (N = 91) wild type GG alleles, 6% (N = 6) AG alleles. 3%(N=3) AA alleles had been reported in this study among the enrolled population Conclusion: These data provide a comprehensive picture of the common α deletion in the Bangladeshi population.