Analysis of ?-globin gene haplotypes in Asian Indians: origin and spread of ?-thalassaemia on the Indian subcontinent

Varawalla, Nermeen; Fitches, Alison C.; Old, John

doi:10.1007/bf00220475

Cited by 107 publications

(62 citation statements)

References 18 publications

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“…Five mutations, IVSI-5(G[C), IVSI-1(G[T), 619-bp del, Codon 41/42(-TCTT) and Codon 8/9(?G) accounted for 90% of all mutations (Kazazian et al 1984;Thein et al 1988). The results were replicated in follow-up collaborative studies undertaken in Indian and Western centres, mainly focused on the populations of Gujarat, Punjab and Maharashtra (Varawalla et al 1991a(Varawalla et al , 1992Garewal et al 1994). On the basis of these findings it therefore was assumed that in India the prevalence of b-thalassaemia was highest in the Sindhi and Punjabi communities, and it was only towards the end of the twentieth century that reports from other Indian states demonstrated the wide distribution and extensive heterogeneity of b-thalassaemia mutations in different Indian sub-populations.…”

Section: Introductionmentioning

confidence: 66%

Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes

Sinha

Black

Agarwal

et al. 2009

HUGO J

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Thalassaemia and sickle cell disease have been recognized by the World Health Organization as important inherited disorders principally impacting on the populations of low income countries. To create a national and regional profile of b-thalassaemia mutations in the population of India, a meta-analysis was conducted on 17 selected studies comprising 8,505 alleles and offering nearnational coverage for the disease. At the national level 52 mutations accounted for 97.5% of all b-thalassaemia alleles, with IVSI-5(G[C) the most common disease allele (54.7%). Population stratification was apparent in the mutation profiles at regional level with, for example, the prevalence of IVSI-5(G[C) varying from 44.8% in the North to 71.4% in the East. A number of major mutations, such as Poly A(T[C), were apparently restricted to a particular region of the country, although these findings may in part reflect the variant test protocols adopted by different centres. Given the size and genetic complexity of the Indian population, and with specific mutations for b-thalassaemia known to be strongly associated with individual communities, comprehensive disease registries need to be compiled at state, district and community levels to ensure the efficacy of genetic education, screening and counselling programmes. At the same, time appropriately designed community-based studies are required as a health priority to correct earlier sampling inequities which resulted in the under-representation of many communities, in particular rural and socioeconomically under-privileged groups.

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Section: Introductionmentioning

confidence: 66%

Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes

Sinha

Black

Agarwal

et al. 2009

HUGO J

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“…Among the ␤-thalassemia mutations, IVS1-5 (G➝C) and Hb E are the most common mutations, occurring at percentages of 28.75 and 25, respectively. IVS1-5 (G➝C) happens to be the most frequent mutation in many other parts of India as well, i.e., Punjab, Gujrat, Maharastra, and southern India [2,15,20]. Characterization of the mutation patterns revealed from such study should provide the basis for prenatal diagnosis and genetic counseling of affected individuals.…”

Section: Discussionmentioning

confidence: 99%

“…␤-Thalassemia carriers and ␤-thalassemia major were defined by the phenotypic characteristics (high levels of Hb A 2 , >3.5%, and transfusion dependence) [14]. Common mutations IVS1-1 (G➝T), IVS1-5 (G➝C), codon 8/9 (+G), codon 26 (G➝A), codon 41/42 (−TCTT), codon 15 (G➝A), and codon 30 (G➝C) described in the Indian population [15] were screened by ARMS. Five different mutations were detected as shown in Table II: IVS1-5 (G➝C), Hb E:codon 26 (G➝A), codon 41/42 (−TCTT), codon 15 (G➝A), and codon 30 (G➝C).…”

Section: Spectrum Of ␤-Thalassemia Mutations In Eastern Indiamentioning

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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“…The genomic DNA was first amplified by Polymerase Chain Reaction (PCR) by using published primers [17][18][19], followed by restriction digestion and agarose gel inspection. The presence of an A or T nucleotide at in the 6 th codon of the β-globin was confirmed for all the DNA samples by using restriction enzyme DdeI analysis.…”

Section: Methodsmentioning

confidence: 99%

Fetal Haemoglobin and β -globin Gene Cluster Haplotypes among Sickle Cell Patients in Chhattisgarh

Bhagat

Patra²,

Thakur³

2013

JCDR

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Analysis of ?-globin gene haplotypes in Asian Indians: origin and spread of ?-thalassaemia on the Indian subcontinent

Cited by 107 publications

References 18 publications

Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes

Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes

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

Fetal Haemoglobin and β -globin Gene Cluster Haplotypes among Sickle Cell Patients in Chhattisgarh

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