Molecular basis of β-thalassemia in the Maldives

Abstract

We have systematically analyzed β-thalassemia genes using polymerase chain reaction-related techniques, dot-blot hybridization with oligonucleotide probes, allele specific-polymerase chain reaction, and sequencing of amplified DNA fragments from 41 unrelated patients, including 37 β-thalassemia homozygotes, three with β-thalassemia/Hb E, and one with β-thalassemia/Hb S. Four different β-thalassemia mutations were detected in 78 alleles. These are the IVS-I-5 (G→C), codon 30 (AGG→ACG) [also indicated as IVS-I (-1)], IVS-I-1 (G→A), and codons 41/42 (-TTCT) mutations. The distribution of the β-thalassemia mutations in the Maldives is 58 alleles (74.3%) with the IVS-I-5 (G→C) mutation, 12 (15.4%) with the codon 30 (AGG→ACG) mutation, seven (9%) with the IVS-I-1 (G→A) mutation, and one with the codons 41/42 (-TTCT) mutation. The first three mutations account for 98.7% of the total number of β-thalassemia chromosomes studied. These mutations are clustered in the region spanning 6 bp around the junction of exon 1 and the first intervening sequence of the β-globin gene. These observations have significant implications for setting up a thalassemia prevention and control program in the Maldives. Analysis of haplotypes and frameworks of chromosomes bearing each β-thalassemia mutation suggested that the origin and spread of these mutations were reflected by the historical record.