β-Thalassemia and β^A globin gene haplotypes in Mexican mestizos

Abstract

β-globin haplotypes of 20 β-thalassemia (β-thal) and 87 β^A Mexican mestizo chromosomes were analyzed to ascertain the origin of the β-thal alleles and the frequencies and distribution of the β^A haplotypes among northwestern Mexican mestizos. Sixteen β-thal chromosomes carried six Mediterranean alleles [five codon 39 C→T; two IVS1:1 G→A; two IVS1:5 G→A; three IVS1:110 G(A; one codon 11 (–T) and three (δβ)°-thal]; the remaining four were linked to three rare alleles (two –28 A→C and one each: –87 C→T and initiation codon ATG→GTG). Among the 87 β^A chromosomes, 17 different 5′ haplotypes with frequencies for 1, 3, 2 and 5 of 39.0%, 17. 2%, 9.2% and 6.9%, respectively, were observed. The β-haplotype analysis showed that 13 out of 16 Mediterranean chromosomes could easily be explained by gene migration; however, one codon 39 associated with haplotype 4 (– – – – + + –), one IVS1:1 with haplotype 1(+ – – – – + +) and one IVS1:5 G→A, may represent separate mutational events. Analysis of the rare alleles showed that the –28 A→C mutation was associated with the commonest β^A haplotype in Mexican mestizos, Mediterraneans and the total world population; therefore an independent origin cannot be ruled out. The –87 C→T and initiation codon ATG→GTG were found with β-haplotypes different from the reported ones, suggesting an indigenous origin.