Aghajani Faeghe, Mahdavi Mohammad Reza, Kosaryan Mehrnoush, Mahdavi Mehrad, Hamidi Mohaddase, Jalali Hossein
Thalassemia Research Center, Mazandaran University of Medical Sciences.
Sina Mehr Research Center.
Genes Genet Syst. 2017 May 13;91(6):311-313. doi: 10.1266/ggs.16-00005. Epub 2016 Dec 21.
Carrier frequency of the β allele has been reported to be 0.19% in Mazandaran province, northern Iran. Haplotype analysis of the β allele helps trace the origin of its encoded hemoglobin (Hb) variant, Hb S, in a region. The aim of this study was to investigate the haplotypes associated with β alleles in Mazandaran province. Capillary electrophoresis was carried out to detect individuals suspected to have a β allele(s). DNA analysis (PCR-RFLP) was used for final confirmation. To identify 5' to 3' β-globin gene cluster haplotypes associated with β alleles, family linkage analysis was applied. Six polymorphic sites (HincII 5' to ε, XmnI 5' to γ, HindIII in γ, HindIII in γ, HincII 3' to ψβ and AvaII in β) were investigated using the PCR-RFLP method. Five different haplotypes were linked to β alleles, while β alleles were associated with nine haplotypes. Among the β alleles, 53.9% were associated with the Benin (----++) haplotype, and the Arab-Indian (+++-++) haplotype had the second-highest frequency (23%). Unlike southern provinces, where the Arab-Indian haplotype is prominent, the Benin haplotype is the most frequent haplotype in northern Iran, and this may represent a founder effect. Since the Benin haplotype does not carry the XmnI polymorphism 5' to the γ gene, which is responsible for high expression of Hb F, a severe form of sickle cell disease can be anticipated in patients that are homozygous for the β allele in the northern region.
据报道，伊朗北部马赞德兰省β等位基因的携带频率为0.19%。对β等位基因进行单倍型分析有助于追踪该地区其编码的血红蛋白（Hb）变体Hb S的起源。本研究的目的是调查马赞德兰省与β等位基因相关的单倍型。采用毛细管电泳检测疑似携带β等位基因的个体。DNA分析（PCR-RFLP）用于最终确认。为了确定与β等位基因相关的5'至3'β珠蛋白基因簇单倍型，应用了家系连锁分析。使用PCR-RFLP方法研究了六个多态性位点（ε基因5'端的HincII、γ基因5'端的XmnI、γ基因中的HindIII、γ基因中的HindIII、ψβ基因3'端的HincII和β基因中的AvaII）。有五种不同的单倍型与β等位基因连锁，而β等位基因与九种单倍型相关。在β等位基因中，53.9%与贝宁单倍型（----++）相关，阿拉伯-印度单倍型（+++-++）频率次之（23%）。与阿拉伯-印度单倍型占主导的南部省份不同，贝宁单倍型是伊朗北部最常见的单倍型，这可能代表了奠基者效应。由于贝宁单倍型在γ基因5'端不携带负责Hb F高表达的XmnI多态性，预计北部地区β等位基因纯合的患者会出现严重形式的镰状细胞病。
