The same beta-globin gene mutation is present on nine different beta-thalassemia chromosomes in a Sardinian population.

Pirastu, Mario; Galanello, Renzo; Doherty, Mark; Tuveri, T; Cao, Antonio; Kan, Yuet Wai

doi:10.1073/pnas.84.9.2882

Cited by 53 publications

(25 citation statements)

References 28 publications

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“…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). Its distribution in the Arab world is more or less consistent with the reign of the Roman Empire, which extended up to the fifth century BC.…”

Section: Introductionmentioning

confidence: 71%

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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Section: Introductionmentioning

confidence: 71%

Epidemiological profile of common haemoglobinopathies in Arab countries

2012

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“…Moreover, their analysis may be an important tool to track the origin, evolution and spread of a specific mutant gene. This type of study applied to the world wide spread sickle gene [3][4][5] and to P°-thalassemia Sardinian type [6] has shown that different combina tions of restriction endonuclease patterns (haplo types) may be linked to the same pathological gene even within a single population [4][5][6]. In the majority of cases the origin of this diversity has been accounted for by multiple crossing overs in a 'hot spot' region for recombinations between the vpP and the p gene [7], but in some cases multiple (sickle or p° 39 nonsense) mutations must have occurred in order to explain all the patterns observed.…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of Italian Chromosomes Carrying the Lepore Boston Gene

Camaschella¹,

Serra²,

Bertero³

et al. 1989

Acta Haematol

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Hemoglobin Lepore Boston is characterized by abnormal non-α-chains that are the product of a fusion δβ gene originated from an unequal crossing over between misaligned δ and β genes. The investigation of the restriction fragment length polymorphisms (RFLP) of the β-globin gene cluster in 18 Italian Lepore Boston chromosomes indicates that the hybrid gene is linked to two RFLP patterns. The majority of chromosomes show a pattern which corresponds to haplotype V and a minority to haplotype I according to Orkin’s classification. A single Hb Lepore Boston homozygote was homozygous for haplotype V. The two haplotypes differ only for a single site 3´ to the β cluster. Our data allow the speculation that in Italy the Lepore Boston gene might be the result of multiple recombination events.

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“…Sardinian population is genetically separated from that of the rest of Italy as well as from other European populations, due to strong genetic drift. All the monogenic disorders analysed, such as thalassemia (Pirastu et al, 1987), seem to be associated with a single founder mutation throughout the island. Therefore, it seems possible that such a founder effect could also be identified for a complex disease like cancer.…”

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confidence: 99%

Identification of a founder BRCA2 mutation in Sardinia

et al. 2000

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Breast cancer is the most common malignancy in women, with an incidence that varies between 40 and 90 per 100 000 (standardized rate) worldwide. Breast cancer is the most frequent female tumour in Italy, representing about 25% of all female tumours as reported in Italian registries (Zanetti et al, 1997).A positive family history is known to be a high risk factor for developing the disease: 5-10% of all breast cancers arise in individuals carrying a germline mutation and are usually considered hereditary forms (Claus et al, 1991). Two major breast cancersusceptibility genes, BRCA1 and BRCA2, have been cloned (Miki et al, 1994;Wooster et al, 1995) and both are thought to account for 30-60% of hereditary breast cancer (Serova et al, 1997;Szabo et al, 1997;Vehmanen et al, 1997aVehmanen et al, , 1997b. However, large-scale mutation analyses conducted in several populations suggest the existence of additional breast cancer-susceptibility gene(s). BRCA1 mutations are responsible for the majority of familial breast cancer associated with ovarian carcinoma, for about 50% of cases with breast cancer alone and for very few male breast cancer cases (Easton et al, 1993;Stratton et al, 1994;Narod et al, 1995). It has been estimated that women carrying a germline mutation in BRCA1 have a risk ranging from 80 to 90% for developing breast cancer and from 44 to 63% for developing ovarian cancer (Easton et al, 1993(Easton et al, , 1995Ford et al, 1994; Miki et al, 1994;Wooster et al, 1994). BRCA2 mutations account for a similar proportion of inherited breast cancer and are frequently associated with male breast cancer (Wooster et al, 1995). Breast cancer risk in females carrying BRCA2 mutations is calculated to be similar to that conferred by BRCA1 mutations (Easton et al, 1993Ford et al, 1994; Miki et al, 1994;Wooster et al, 1994). BRCA1 and particularly BRCA2 families are often affected by other tumours such as prostate, liver, pancreas, lung, stomach and colorectum (Wooster et al, 1995;Gudmundsson et al, 1996;Phelan et al, 1996;Thorlacius et al, 1996;Vehmanen et al, 1997b;Tonin et al, 1998). Except for higher incidences of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 of BRCA2 (the so-called ovarian cancer cluster region [OCCR]; Gayther et al, 1997), no other significant association between genotype and phenotype was described. BRCA1 and BRCA2 mutations are for the most part frame-shifts due to small deletions leading to premature translation termination (Wooster et al, 1995;Phelan et al, 1996;Tavtigian et al, 1996;Gayther et al, 1997).Some of these mutations are prevalent in genetically homogeneous populations as a consequence of a founder effect. A single BRCA2 mutation accounts for the majority of hereditary breast cancer in Iceland Thorlacius et al, 1996) and for 40% of male breast cancer cases , whereas three different founder mutations (185delAG and 5382insC in BRCA1, and 6174delT in BRCA2) have a high frequency in Ashkenazi Jews (Roa et al, 1996). Although at different rates, BRCA1 and BRCA2 f...

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The same beta-globin gene mutation is present on nine different beta-thalassemia chromosomes in a Sardinian population.

Cited by 53 publications

References 28 publications

Epidemiological profile of common haemoglobinopathies in Arab countries

Epidemiological profile of common haemoglobinopathies in Arab countries

Molecular Characterization of Italian Chromosomes Carrying the Lepore Boston Gene

Identification of a founder BRCA2 mutation in Sardinia

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