Morales Karina R, Magaña Maria T, Ibarra Bertha, Perea Francisco J
División de Genetica, Centro de Investigación Biomédica de Occidente, Centro Medico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
Hemoglobin. 2009;33(1):66-71. doi: 10.1080/03630260802625923.
beta-Globin haplotypes have been used to investigate the origin and spread of beta-globin mutations such as Hb S [beta 6(A3)Glu-->Val, GAG>GTG], Hb E [beta 26(B8)Glu-->Lys, GAG>AAG], and beta-thalassemia (beta-thal). Molecular analyses revealed the presence of 17 beta-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 beta-globin gene.
β-珠蛋白单倍型已被用于研究β-珠蛋白突变的起源和传播，如Hb S[β6(A3)谷氨酸→缬氨酸，GAG>GTG]、Hb E[β26(B8)谷氨酸→赖氨酸，GAG>AAG]和β-地中海贫血(β-地贫)。分子分析显示墨西哥人群中存在17种β-地贫突变；其中最常见的是无义密码子39(C>T)、内含子1-1(G>A)、内含子1-110(G>A)和-28(A>C)。为了增进我们对其起源的了解，我们通过限制性片段长度多态性分析了5'单倍型。观察到密码子39突变(n = 17)与五种5'单倍型相关：1型(59%)、2型(23%)以及4型、6型和9型(各6%)。内含子1-1突变(n = 15)与五种5'单倍型相关：1型(73.6%)、2型、3型、5型和11型(各6.6%)，而内含子1-110突变(n = 9)和-28突变(n = 1)仅与单倍型1相关。在所研究的人群中，密码子39和内含子1-1突变显示多中心起源，而内含子1-110和-28突变有明显的单一起源。需要进一步研究来分析β-珠蛋白基因周围的多态性。
