Boudrahem-Addour Nassima, Zidani Nadia, Carion Nathalie, Labie Dominique, Belhani Meriem, Beldjord Cherif
Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumediène, Alger, Algérie.
Hemoglobin. 2009;33(1):24-36. doi: 10.1080/03630260802626061.
This study concerns the molecular characterization of beta-thalassemia (beta-thal) alleles in 210 chromosomes. In the studied population, mutations were detected in 98% of the beta-thalassemic chromosomes. Twenty-one molecular defects have been found, where the five dominant mutations, IVS-I-110 (G>A), nonsense mutation at codon 39 (C>T), the frameshift codon (FSC) 6 (-A), IVS-I-1 (G>A), and IVS-I-6 (T>C), account for 80% of the independent chromosomes. Among the remaining alleles, 16 different mutations were identified, half of them being described for the first time in Algeria. These include the -101 (C>T) and the -90 (C>T) mutations in the distal and proximal promoter elements, respectively, the FSC 8 (-AA), IVS-I-5 (G>T), IVS-I-128 (T>G), FSC 47 (+A), IVS-II-1 (G>A), and the substitution in the polyadenylation signal (poly A) site AATAAA>AATGAA. Haplotype analyses on rare variants were performed. The possible origin of these mutations either by founder effect or by migrations is discussed, and raises the question of an adequate strategy to be used adapted to socio-economical status.
本研究涉及210条染色体上β地中海贫血（β-地贫）等位基因的分子特征。在研究人群中，98%的β-地贫染色体检测到突变。已发现21种分子缺陷，其中5种主要突变，即IVS-I-110（G>A）、密码子39处的无义突变（C>T）、移码密码子（FSC）6（-A）、IVS-I-1（G>A）和IVS-I-6（T>C），占独立染色体的80%。在其余等位基因中，鉴定出16种不同突变，其中一半是在阿尔及利亚首次描述。这些突变包括分别位于远端和近端启动子元件中的-101（C>T）和-90（C>T）突变、FSC 8（-AA）、IVS-I-5（G>T）、IVS-I-128（T>G）、FSC 47（+A）、IVS-II-1（G>A）以及聚腺苷酸化信号（poly A）位点AATAAA>AATGAA的替换。对罕见变异进行了单倍型分析。讨论了这些突变可能源于奠基者效应或迁移，并提出了根据社会经济状况采用适当策略的问题。
