MOLECULAR-BASIS OF BETA-THALASSEMIA IN THE MALDIVES

We have systematically analyzed beta-thalassemia genes using polymeras e chain reaction-related techniques, dot-blot hybridization with oligo nucleotide probes, allele specific-polymerase chain reaction, and sequ encing of amplified DNA fragments from 41 unrelated patients, includin g 37 beta-thalassemia homozygotes, three with beta-thalassemia/Hb E, a nd one with beta-thalassemia/Hb S. Four different beta-thalassemia mut ations were detected in 78 alleles. These are the IVS-I-5 (G-->C), cod on 30 (A (G) under bar G-->A (C) under bar G) [also indicated as IVS-I (-1)], IVS-I-1 (G-->A), and codons 41/42 (-TTCT) mutations. The distr ibution of the beta-thalassemia mutations in the Maldives is 58 allele s (74.3%) with the IVS-I-5 (G-->C) mutation, 12 (15.4%) with the codon 30 (A (G) under bar G-->A (C) under bar G) mutation, seven (9%) with the IVS-I-1 (G-->A) mutation, and one with the codons 41/42 (-TTCT) mu tation. The first three mutations account for 98.7% of the total numbe r of beta-thalassemia chromosomes studied. These mutations are cluster ed in the region spanning 6 bp around the junction of exon 1 and the f irst intervening sequence of the beta-globin gene. These observations have significant implications for setting up a thalassemia prevention and control program in the Maldives. Analysis of haplotypes and framew orks of chromosomes bearing each beta-thalassemia mutation suggested t hat the origin and spread of these mutations were reflected by the his torical record.