Diversity of sequence haplotypes associated with β-thalassaemia mutations in Algeria: implications for their origin

Perrin, Pascale; Bouhassa, Rachid; Mselli, Leı̈la; Garguier, Nathalie; Nigon, Victor; Bennani, C.; Labie, Dominique; Trabuchet, G

doi:10.1016/s0378-1119(98)00200-5

Cited by 24 publications

(15 citation statements)

References 20 publications

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“…The AT dinucleotide insert accompanies either the presence or the absence of a T➝A replacement at −528, showing a +ATA,−T event as reported previously [23]. These variants have also been described by Perrin et al [24], Ragusa et al [25], and Gasperini et al [26] mostly in Sicily, Algerian, and Sardinian populations. The (AT) 9 (T) 5 motif has been studied with varying implications.…”

Section: Discussionsupporting

confidence: 78%

“…This type of molecular heterogeneity underlies the wide spectrum of clinical manifestations of the disease. In brief, this analysis revealed the association of some common ␤-thalassemia mutations with the varied haplotypes which would be generated due to the large size of the chromosomal portion and the existence of hot spots for meiotic recombinations leading to many recombinations, substitutions, or conversions with the adjacent regions [24]. This exercise gives us an opportunity to determine the allele diversity associated with the ␤-thalassemia mutations; it also allows us to study the nucleotide variations in the ␤-globin gene cluster and their associations with the ␤-thalassemia mutations in order to explore the genetic basis of the clinical diversity of the disease in eastern part of India, primarily the state of West Bengal.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 78%

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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“…IVS-I-110 is associated with four RFLP haplotypes (I, II, IV and IX) in Turkey, suggesting that it may have originated in Turkey (Anatolia) probably in the Neolithic period, and then spread to other parts in the Eastern Mediterranean area and North Africa by the Greeks, Phoenicians or later by Othmans (Haj Khelil et al 2010;Tadmouri et al 2001;Tadmouri and Gulen 2003). Sequence haplotypes have supported the latter suggestion since it was found that IVS-I-110 was associated with six haplotypes in Turkey, two in Lebanon and two in Algeria and Tunisia (Haj Khelil et al 2010;Perrin et al 1998;Tadmouri et al 2001;Zahed et al 2002). & Codon 39 is a Western Mediterranean mutation of possibly a Roman origin, having its highest worldwide prevalence in Sardinia where it is associated with nine different haplotypes (Pirastu et al 1987).…”

Section: Introductionmentioning

confidence: 82%

Epidemiological profile of common haemoglobinopathies in Arab countries

2012

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Haemoglobinopathies including the thalassemias and sickle cell disease are known to be prevalent inherited disorders in most Arab countries with varying prevalence rates and molecular characterisation. β-thalassemia is encountered in polymorphic frequencies in almost all Arab countries with carrier rates of 1-11 % and a varying number of mutations. The most widespread mutation in Lebanon, Egypt, Syria, Jordan, Tunisia and Algeria is the IVS-I-110 (G>A). In the Eastern Arabian Peninsula, the Asian Indian mutations (IVS-I-5 (G>C), codons 8/9 (+G) and IVS-I (−25 bp del)) are more common. The α-thalassemias are encountered in the majority of Arab countries in frequencies ranging from 1 to 58 % with the highest frequencies reported from Gulf countries. The (−α 3.7 ) mutation is the most frequent followed by the non-deletional α2 polyadenylation signal mutation (AATAAA>AATAAG) and the α2 IVS1 5-bp deletion. The rates of sickle cell trait in Arab countries range from 0.3 to 30 %, with the Benin, the Arab-Indian and the Bantu haplotypes constituting the bulk of the haplotypes, leading to two major phenotypes; a mild one associated with the Arab-Indian and a severe one with the Benin and Bantu haplotypes. Public health approaches targeting prevention of haemoglobinopathies in Arab countries include newborn screening for sickle cell disease, and premarital screening for carriers of β-thalassemia and sickle cell disease. These services are still patchy and inadequate in many Arab countries recommending the upgrade of these services with strengthening of the education and training of health care providers and raising public awareness on the feasibility of prevention and care for haemoglobinopathies.

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“…However, these estimates ignore possible homogenization of the SMN genes by means of gene conversion. Gene conversion can increase sequence diversity by exchanging mutations or polymorphisms from a pseudogene to its functional coding counterpart (Killeen et al 1998;Patrinos et al 1998;Perrin et al 1998;Watnick et al 1998), or it can homogenize sequences between duplicated regions thereby reducing genetic diversity (Slighton et al 1987;Fitch et al 1990;Papdakis and Patrinos 1999). In both cases, gene conversion would obscure evolutionary relationships inferred by molecular clock data, as has been demonstrated for a number of loci (Boissinot et al 1998;Kitano and Saitou 1999;White and Crother 2000).…”

Section: Discussionmentioning

confidence: 99%

SMN gene duplication and the emergence of the SMN2 gene occurred in distinct hominids: SMN2 is unique to Homo sapiens

2001

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The spinal muscular atrophy (SMA) region on chromosome 5q13 contains an inverted duplication of about 500 kb, and deleterious mutations in the survival motor neuron 1 (SMN1) gene cause SMA, a common lethal childhood neuropathy. We have used a number of approaches to probe the evolutionary history of these genes and show that SMN gene duplication and the appearance of SMN2 occurred at very distinct evolutionary times. Molecular fossil and molecular clock data suggest that this duplication may have occurred as recently as 3 million years ago in that the position and identity repetitive elements are identical for both human SMN genes and overall sequence divergence ranged from 0.15% to 0.34%. However, these approaches ignore the possibility of sequence homogenization by means of gene conversion. Consequently, we have used quantitative polymerase chain rection and analysis of allelic variants to provide physical evidence for or against SMN gene duplication in the chimpanzee, mankind's closest relative. These studies have revealed that chimpanzees have 2-7 copies of the SMN gene per diploid genome; however, the two nucleotides diagnostic for exons 7-8 and the SMNdelta7 mRNA product of the SMN2 gene are absent in non-human primates. In contrast, the SMN2 gene has been detected in all extant human populations studied to date, including representatives from Europe, the Central African Republic, and the Congo. These data provide conclusive evidence that SMN gene duplication occurred more than 5 million years ago, before the separation of human and chimpanzee lineages, but that SMN2 appears for the first time in Homo sapiens.

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Diversity of sequence haplotypes associated with β-thalassaemia mutations in Algeria: implications for their origin

Cited by 24 publications

References 20 publications

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

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

Epidemiological profile of common haemoglobinopathies in Arab countries

SMN gene duplication and the emergence of the SMN2 gene occurred in distinct hominids: SMN2 is unique to Homo sapiens

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