Spectrum of ? thalassemia mutations and their linkage to ?-globin gene haplotypes in the Indo-Mauritians

Kotea, Navaratnam; Ramasawmy, Rajendranath; Lu, Changyuan; Fa, Nathalie Sem; Gérard, Nathalie; Beesoon, Sanjay; Ducrocq, Rolande; Surrun, Soondal Koomar; Nagel, Ronald L.; Krishnamoorthy, Rajagopal

doi:10.1002/(sici)1096-8652(200001)63:1<11::aid-ajh3>3.0.co;2-d

Cited by 10 publications

(5 citation statements)

References 16 publications

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“…In this report, association of β-thalassemia mutations with the β-globin gene frameworks coincided with the majority reports (6)(7)(8)(9)(10)(14)(15)(16)(17) . With the exception in codon 41/42 (-TCTT), there is only one type of β-globin gene framework in each β-thalassemia mutations in this study.…”

Section: Discussionsupporting

confidence: 86%

Associations of Common -Thalassemia Mutations With -Globin Gene Frameworks in Northern Thailand

Sanguansermsri

Shimbu

Wongvilairat

et al. 2017

AJSTD

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This study aimed to characterize polymorphism of the b-globin gene (framework) among common b-thalassemia mutations found in northern Thailand. Thirty-one homozygous b-thalassemia major patients admitted to Chiang Mai University Hospital were identified using direct DNA sequencing method. Among 15 patients with homozygous of codon 41/42 (-TCTT), eight were homozygous of framework 1 (FW1), one was homozygous of FW3A, and the remainders were heterozygousof FW1 and FW3A. The gene frequencies of FW1 and FW3A in the patients were 0.733 (22/ 30) and 0.267 (8/30), respectively. All 11 patients with homozygous of codon 17 (A-T) were homozygous of FW3A, while three patients with homozygous of intron 1 nt 1 (G-T) were homozygous of FW1. Both patients with homozygous of codon 71/72 (+A) were FW3A. In this report, the numbers of b-globin gene frameworks were restricted in each b-thalassemia mutation. This investigation may provide further information for the study of the evolution of common mutations causing b-thalassemia major in northern Thailand.

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Section: Discussionsupporting

confidence: 86%

Associations of Common -Thalassemia Mutations With -Globin Gene Frameworks in Northern Thailand

Sanguansermsri

Shimbu

Wongvilairat

et al. 2017

AJSTD

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“…This indicates that the sequence repeat polymorphisms present in the ␤-globin gene cluster are common polymorphisms [6,7,10,16], and although they may not be necessarily associated with the hematological characteristic of ␤-thalassemia, they could play an important role in subtle expression of the locus as a whole [16]. We speculate that the genetic determinant may lie either in other unexamined cisacting sequences, i.e., phylogenetically conserved regions of the LCR, 5Ј of the -globin gene, 5Ј of the ␦-globin gene, other 3Ј sequences of the ␤-globin gene, or elsewhere in the genome, which may involve the function of a gene encoding for a transcription factor regulating the function of the ␤-globin gene [27,30]. With the recent success of the Human Genome Project, it is anticipated that more genetic modifiers and environmental factors will be discovered that can help in understanding the variations in phenotypes of ␤-thalassemia.…”

Section: Discussionmentioning

confidence: 98%

“…The haplotypes associated with this mutation are also represented among the normal alleles of this population. In India this mutation is strongly linked with eight different haplotypes and two different sequence frameworks, 2 and 3 [27], but it is also found in the same percentage in other populations, such as Indo-Mauritians, with three varied haplotypes on an identical sequence framework [27]. Recently Bandyopadhyay et al [2] found this mutation to be strongly linked (82%) with a + − − − − + haplotype (HindII , HindIII ␥ G , HindIII ␥ A , HindII 5Ј ␤, HindII 3Ј ␤, and HinfI ␤) in an eastern Indian population.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of β‐thalassemia mutations and their association with allelic sequence polymorphisms at the β‐globin gene cluster in an eastern Indian population

et al. 2002

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In this report, the spectrum of ␤-thalassemia mutations and genotype-to-phenotype correlations were defined in large number of patients (␤-thalassemia carriers and major) with varying disease severity in an Eastern Indian population mainly from the state of West Bengal. The five most common ␤-thalassemia mutations were detected, which included IVS1-5 (G➝C), codon 15 (G➝A), codon 26 (G➝A), codon 30 (G➝C), and codon 41/42 (−TCTT). These accounted for 85% in 80 ␤-thalassemic alleles deciphered from 56 patients, including ␤-thalassemia major and carriers, and 15% of alleles remained uncharacterized in these patients. Expression of the human ␤-globin gene is regulated by an array of cis-acting DNA elements, including five DNase I hypersensitive sites (HSs) in the locus control region (LCR), promoters that incorporate certain silencer elements, and enhancers at 3 of the ␤-globin gene. For detailed studies and to understand the molecular basis of ␤-thalassemia, we studied two groups of subjects: a group of 12 patients from four families having ␤-thalassemia major and carrier phenotype and a control group of 26 healthy individuals. In these two groups, we examined portions of the ␤-globin gene locus control region HSs 1, 2, 3, and 4, which included the (CA) x (TA) y repeat motif, the (AT) x N y (AT) z repeat motif, the inverted repeat sequence TGGGGACCCCA, the promoter region of the G ␥-globin gene, an (AT) x (T) y repeat 5 of the silencer region, and the ␤-globin gene and its 3 flanking region. We investigated the allelic sequence polymorphisms in these regions and their association with the ␤-thalassemia mutations to know the possible genotype-phenotype relationship in ␤-thalassemia patients. An analysis of cisacting regulatory regions showed varied sequence haplotypes associated with some frequent ␤-thalassemia mutations in this Eastern Indian population. Am.

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“…Conversely, this mutation was linked to haplotypes I and III in Hormozgan and Fars provinces 19 . Mansoori et al have shown that this mutation was predominantly associated with haplotype IV in Azarbayjan-Sharghi province 16 . The association of this mutation with haplotypes III and V among the Turkish population 23 and with haplotypes I and III among the Palestinian 24 and Lebanese 25 populations have been reported, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…The most common mutation was c.315+1G>A (26.66%), followed by c.92+5G>C (10%) and c.93-21G>A (3.33%). The c.315+1G>A mutation was found to be the most frequent mutation in the Kurdistan, Azarbayjan-Sharghi, and Fars provinces of Iran as well as most of the Arab countries 14 - 16 .…”

Section: Discussionmentioning

confidence: 99%

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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Spectrum of ? thalassemia mutations and their linkage to ?-globin gene haplotypes in the Indo-Mauritians

Cited by 10 publications

References 16 publications

Associations of Common -Thalassemia Mutations With -Globin Gene Frameworks in Northern Thailand

Associations of Common -Thalassemia Mutations With -Globin Gene Frameworks in Northern Thailand

Spectrum of β‐thalassemia mutations and their association with allelic sequence polymorphisms at the β‐globin gene cluster in an eastern Indian population

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

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