Two β‐globin cluster‐linked polymorphic loci in thalassemia patients of variable levels of fetal hemoglobin

Abstract

The senegal haplotype and the polymorphism at -158 of G(gamma) was linked to the high-HbF phenotype.

Persistent Fetal γ-Globin Expression in Adult Transgenic Mice following Deletion of Two Silencer Elements Located 3′ to the Human Aγ-Globin Gene

“…Furthermore, the configuration (AT) 9 T 5 of the polymorphic sequence motif residing 0.5 kb 5′ to the β-gene has been considered to confer high γ-globin levels in β-thalassemia patients in association with the XmnI polymorphism (12)(13)(14), although other studies (15) have found no effect. Furthermore, analysis of mutants with rare point mutations either in the Gγ or Aγ promoter associated with a hereditary persistence of fetal hemoglobin (HPFH) phenotype (11,16) have provided insights for the mechanisms of continued HbF synthesis based on the alterations in DNAprotein binding sites, resulting either in the creation of a new motif that allows trans-activator binding, or in the abolishment of a repressor protein binding motif, leading to de-repression of fetal genes (11,16).…”

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

“…Additionally, with hematological stress (e.g. Sickle Cell disease, Beta Thalasemia, hemolysis, pregnancy), the XmnI polymorphism has been shown to be at least partly responsible for an even greater increase in total Hb F and F cell levels [1,7,18,25,33,60,66,94,98].…”

The study of sequence configuration and functional impact of the (AC)n(AT)xTy motif in human β‐globin gene promoter

“…Cycle sequencing was performed on a The (AC) 3 (AT) 7 T 5 motif is in bold and is found to be associated with high HbF level in our patient cohort. Note.…”

“…The three different type of (AC) n (AT) x T y motifs were subcloned as NheI-Eco72I fragments into the respective sites of the pCR2.1_ATxTybHSneo vector which consisted of a human b-globin gene (from +474 (Eco72I) to +3,422 (BglII) with relative to the cap site of the b-globin gene), HS2 and HS3 of the human b-globin LCR and a neomycin resistance gene. Using this strategy, three different recombinant plasmids were generated: pCR2.1_ATxTybHSneo (AC) 2 (AT) 8 T 5 , (AC) 3 (AT) 7 T 5 , and (AC) 2 (AT) 9 T 5 . The map of the construct is shown in Fig.…”

“…Alleviation of the clinical severity of the disease is observed in patients who coinherited hereditary persistence of hemoglobin (HPFH), where fetal g-globin gene is expressed (HbF: a 2 g 2 ) during adult life [2]. Studies on thalassaemia patients of mainly European and African descent showed that different (AT) 9 T 5 configurations in the promoter led to variations in bglobin gene expression [3]. As b-globin gene expression requires the cooperation of a variety of regulatory elements, any variations in these regulatory regions may modify the clinical phenotype of the patients [4,5].…”