Haplotypes inside the beta-globin gene: use as new biomarkers for beta-thalassemia prenatal diagnosis in north of Iran

Hashemi‐Soteh, Mohammad Bagher; Mousavi, Seyed Saeed; Tafazoli, Alireza

doi:10.1186/s12929-017-0396-y

Cited by 10 publications

(9 citation statements)

References 16 publications

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“…The strong linkage disequilibrium of beta gene cluster haplotypes with prevalent mutations has been reported previously 20 - 22 . In our population, c.315+1G>A mutation is in linkage disequilibrium with haplotypes III (43.75%), I (31.25%), VII (20%), and IV (5%), respectively .…”

Section: Discussionmentioning

confidence: 68%

Investigation of RFLP Haplotypes β- Globin Gene Cluster in Beta-Thalassemia Patients in Central Iran

Sajadpour

Amini‐Farsani

Motovali-Bashi

et al. 2019

IJHOSCR

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Introduction: Beta-thalassemia is one of the most prevalent inherited blood diseases among Iranians. The aim of this study was to elucidate the chromosomal background of beta-thalassemia mutations in Esfahan province, Iran. Materials and Methods: In this study, we investigated three frequent mutations (c.315+1G>A, c.93-21G>A and c.92+5G>C in β-globin gene, the frequency of RFLP haplotypes, and LD between markers at β-globin gene cluster) in 150 beta-thalassemia patients and 50 healthy individuals. The molecular and population genetic investigations were performed on RFLP markers HindIII in the c.315+1G>A of Gγ (HindIIIG) and Aγ (HindIIIA) genes, AvaII in the c.315+1G>A of β-globin gene and BamHI 3' to the β-globin gene. All statistical analyses were performed using Power Marker software and SISA server. Results: Fifty percent of beta-thalasemia patients were associated with these mutations. Haplotype I was the most prevalent haplotype among beta-thalassemia patients (39.33%) and normal individuals (46%). The commonest c.315+1G>A mutation in our population was tightly linked with haplotype III (43.75%) and haplotype I (31.25%). The second prevalent mutation, c.92+5G>C, was 90%, 6.66%, and 3.33% in linkage disequilibrium with haplotypes I, VII, and III, respectively. The c.93-21G>A mutation indicated a strong association with haplotype I (80%). Conclusion: Our study participants like beta-thalassemia patients from Kermanshah province was found to possess a similar haplotype background for common mutations. The emergence of most prevalent mutations on chromosomes with different haplotypes can be explained by gene conversion and recombination. High linkage of a mutation with specific haplotype is consistent with the hypothesis that chromosomes carrying beta-thalassemia mutations experienced positive selection pressure, probably because of the protection against malaria experienced by beta-thalassemia carriers.

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Section: Discussionmentioning

confidence: 68%

Investigation of RFLP Haplotypes β- Globin Gene Cluster in Beta-Thalassemia Patients in Central Iran

Sajadpour

Amini‐Farsani

Motovali-Bashi

et al. 2019

IJHOSCR

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“…Beside, four intragenic polymorphisms (C2(T > C), IVS‐II‐16(G > C), IVS‐II‐74(T > G), and IVS‐II‐666(C > T)) have been identified, which define three Frameworks. Framework identification could be used as an indirect method in prenatal diagnostic programs to track variant alleles and thus differentiate between normal and mutant alleles (Akhavan‐Niaki et al, 2012 ; Hashemi‐Soteh et al, 2017 ). Furthermore, two other polymorphisms at the UTR region (3′UTR + 34(C > A) and 3′UTR + 101(G > C)) were found.…”

Section: Discussionmentioning

confidence: 99%

Molecular heterogeneity of β‐thalassemia variants in the Eastern region of Morocco

Belmokhtar

Lhousni

Errahhali

et al. 2022

Molec Gen & Gen Med

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Background β‐thalassemia syndromes are the most common hereditary blood disorders in the world and are recognized as a major health problem in Morocco. They are characterized by the reduction or the absence of β‐globin chain synthesis. The severity of the disease depends on the nature of the variants affecting the β‐globin gene ( HBB ), and each ethnic group has its own mutation spectrum. Hereby, we present, for the first time, the molecular profile of β‐thalassemia in the Eastern region of Morocco. Methods This study concerns 39 cases from 33 families who were enrolled in the BRO Biobank. Nineteen were diagnosed with β‐thalassemia major and 20 with β‐thalassemia minor. To detect mutations of the β‐globin gene, we have used RFLP‐PCR and Sanger sequencing. Results Nine known β‐thalassemia variants have been identified. Among these, we reported, for the first time in the Moroccan population, the Czechoslovakian variant C38/39(‐C) at homozygous state. The C39(C > T) was the most frequent variant (72.54%), followed by FSC5(‐CT) (5.88%), FSC6(−A), IVS‐1‐110(G > A), −29(A > G), C38/39(‐C) (3.92% each), and finally by IVS‐I‐1(G > A), IVS‐II‐1(G > A), and −56(G > C) (1.96%). Of particular interest this mutational spectrum of β‐thalassemia is very different from that found in previous studies in Morocco or in other North African countries. Conclusion This study is the first contribution to the description of the molecular profile of β‐thalassemia in the Eastern region of Morocco. It shows the high molecular heterogeneity of β‐thalassemia in our country. Therefore, these results can be valuable for the implementation of carrier screening, genetic counseling, and prenatal diagnosis programs.

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“…The novel haplotype constructed in this study may provide a better representation of the actual genetic background of these mutations than those previously constructed. Previous β-globin gene haplotype studies have had the limitation of a recombination hot spot near the 5′ end of the β-globin gene, which may lead to mistakes in detecting mutated alleles [ 8 , 11 , 13 , 22 ]. To increase the accuracy of the indirect genetic background analysis, the evaluation of new polymorphic sites and molecular analysis of β-thalassemia are investigated [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…Only two DNA polymorphisms on 3′ haplotypes are useful for studying the genetic background of β-globin genes: Ava II (IVS II-16) (rs10768683; C > G), located on the β-globin gene, and Hinf I (rs10837631; T > A), located on the 3′ β-globin gene [ 11 , 12 ]. Newly intragenic polymorphisms of the β-globin gene are informative polymorphisms in haplotype analysis associated with genetic background and clinical linkage studies of β-thalassemia mutations [ 13 , 14 , 15 ]. However, studies of these intergenic polymorphisms have yet to be comprehensively reported for the Thai population [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Background Studies of Eight Common Beta Thalassemia Mutations in Thailand Using β-Globin Gene Haplotype and Phylogenetic Analysis

Karnpean

Tepakhan

Suankul

et al. 2022

Genes

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Single nucleotide polymorphisms are informative for haplotype analysis associated with genetic background and clinical linkage studies of β-thalassemia mutations. Hence, the aim of this study was to investigate five polymorphisms (codon 2 (C/T), IVS II-16 (C/G), IVS II-74 (G/T), IVS II-81 (C/T) and the Hinf I (T/A) polymorphism) on the β-globin gene, related to eight common β-thalassemia mutations in Thailand, including NT-28 (A > G), codon 17 (A > T), codon 19 (A > G), HbE (G > A), IVS I-1 (G > C), IVS I-5 (G > C), codon 41/42 (-TTCT) and IVS II-654 (C > T). The strongest LD (100%) between the β-thalassemia mutation allele and all five SNPs was found in NT-28 (A > G), codon 17 (A > T) and codon 19 (A > G). In the haplotype analysis, we found three haplotypes (H1, H2 and H7) related to Hb E, whereas we only found two haplotypes related to codon 41/42 (-TTCT) (H1, H3) and IVS I-1 (G > C) (H3, H4). Of interest is the finding relating to a single haplotype in the remaining β-thalassemia mutations. Furthermore, phylogenetic tree analysis revealed three clusters of these common β-thalassemia mutations in the Thai population and enabled us to determine the origin of these mutations. Here, we present the results of our study, including four intragenic polymorphisms and the finding that the Hinf I polymorphism could be informative in genetic background analysis, population studies and for predicting the severity of β-thalassemia in Thailand.

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Haplotypes inside the beta-globin gene: use as new biomarkers for beta-thalassemia prenatal diagnosis in north of Iran

Cited by 10 publications

References 16 publications

Investigation of RFLP Haplotypes β- Globin Gene Cluster in Beta-Thalassemia Patients in Central Iran

Investigation of RFLP Haplotypes β- Globin Gene Cluster in Beta-Thalassemia Patients in Central Iran

Molecular heterogeneity of β‐thalassemia variants in the Eastern region of Morocco

Genetic Background Studies of Eight Common Beta Thalassemia Mutations in Thailand Using β-Globin Gene Haplotype and Phylogenetic Analysis

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