Diversity of the 5′ β-Globin Haplotype of Four β-Thalassemia Mutations in the Mexican Population

Abstract

β-Globin haplotypes have been used to investigate the origin and spread of β-globin mutations such as Hb S [β6(A3)Glu→Val, GAG>GTG], Hb E [β26(B8)Glu→Lys, GAG>AAG], and β-thalassemia (β-thal). Molecular analyses revealed the presence of 17 β-thal mutations in the Mexican population; the most frequent of these are the nonsense codon 39 (C>T), IVS-I-1 (G>A), IVS-I-110 (G>A), and −28 (A>C). To improve our knowledge about their origin, we analyzed the 5′ haplotypes by restriction fragment length polymorphism. The codon 39 mutation (n = 17) was observed with five 5′ haplotypes: 1 (59%), 2 (23%), and 4, 6, and 9 (6% each). The IVS-I-1 mutation (n = 15) was found with five 5′ haplotypes: 1 (73.6%), 2, 3, 5, and 11 (6.6% each), whereas the IVS-I-110 (n = 9) and −28 mutations (n = 1) were only associated with haplotype 1. In the population studied, the codon 39 and IVS-I-1 mutations show a multicentric origin, whereas the IVS-I-110 and −28 mutations have an apparent single origin. Further investigation is required for the analysis of the polymorphisms surrounding the β-globin gene.

Keywords:

• β-Globin
• Haplotype
• β-Thalassemia (β-thal)
• Mexico