title: Molecular basis of beta-thalassemia in the Maldives.
abstract: We have systematically analyzed beta-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 beta-thalassemia homozygotes, three with beta-thalassemia/Hb E, and one with beta-thalassemia/Hb S. Four different beta-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 beta-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 beta-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 beta-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 beta-thalassemia mutation suggested that the origin and spread of these mutations were reflected by the historical record.
authors.affiliation: Institute of Genetic Information, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Furuumi
authors.forename: N
authors.initials: N
authors.lastname: Firdous
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Ohta
authors.forename: P
authors.initials: P
authors.lastname: Winichagoon
authors.forename: S
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Y
authors.initials: Y
authors.lastname: Fukumaki
mesh_terms: D000462:Algeria / Q000208:ethnology; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006446:Hemoglobin E / Q000235:genetics; D006451:Hemoglobin, Sickle / Q000235:genetics; D006456:Hemoglobinuria / Q000150:complications / Q000235:genetics; D006801:Humans; D007194:India / Q000208:ethnology; D007195:Indian Ocean Islands / Q000453:epidemiology; D007214:Indonesia / Q000208:ethnology; D008288:Malaria / Q000453:epidemiology; D008296:Malaysia / Q000208:ethnology; D016133:Polymerase Chain Reaction; D011174:Portugal / Q000208:ethnology; D012805:Sickle Cell Trait / Q000150:complications / Q000235:genetics; D017086:beta-Thalassemia / Q000150:complications / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*
chemical_list: D003062:Codon; D006451:Hemoglobin, Sickle; D005914:Globins; D006446:Hemoglobin E