Genetic Background Studies of Eight Common Beta Thalassemia Mutations in Thailand Using β-Globin Gene Haplotype and Phylogenetic Analysis

Single nucleotide polymorphisms are informative for haplotype analysis associated with genetic background and clinical linkage studies of beta-thalassemia mutations. Hence, the aim of this study was to investigate five polymorphisms (codon 2 (C/T), IVS II-16 (C/G), IVS II-74 (G/T), IVS II-81 (C/T) and the Hinf I (T/A) polymorphism) on the beta-globin gene, related to eight common beta-thalassemia mutations in Thailand, including NT-28 (A > G), codon 17 (A > T), codon 19 (A > G), HbE (G > A), IVS I-1 (G > C), IVS I-5 (G > C), codon 41/42 (-TTCT) and IVS II-654 (C > T). The strongest LD (100%) between the beta-thalassemia mutation allele and all five SNPs was found in NT-28 (A > G), codon 17 (A > T) and codon 19 (A > G). In the haplotype analysis, we found three haplotypes (H1, H2 and H7) related to Hb E, whereas we only found two haplotypes related to codon 41/42 (-TTCT) (H1, H3) and IVS I-1 (G > C) (H3, H4). Of interest is the finding relating to a single haplotype in the remaining beta-thalassemia mutations. Furthermore, phylogenetic tree analysis revealed three clusters of these common beta-thalassemia mutations in the Thai population and enabled us to determine the origin of these mutations. Here, we present the results of our study, including four intragenic polymorphisms and the finding that the Hinf I polymorphism could be informative in genetic background analysis, population studies and for predicting the severity of beta-thalassemia in Thailand.

Automated summary

This study investigated five polymorphisms related to eight common beta-thalassemia mutations in Thailand and found strong linkage disequilibrium between certain mutation sites and five SNPs. Haplotype analysis revealed multiple haplotypes associated with specific mutations, and phylogenetic tree analysis determined the origin of these mutations.