β-globin cluster haplotypes in normal individuals and β039-thalassemia carriers from Sardinia, Italy

Abstract

Seven polymorphic sites in the beta-globin cluster in association with specific thalassemia mutations were analyzed in a sample from Sardinia, Italy. In order to verify previous works carried out on normal samples (beta(A)/beta(A)) and family studies on beta-thalassemia homozygotes individuals, the haplotype frequencies in both normal individuals (beta(A)/beta(A)) and beta(0)39-thalassemia carriers (beta(A)/beta0) were studied. In our work chromosomes carrying beta(0)39 mutation are characterized by a prevalence of haplotype II (- + + - + + +) (52%) relative to haplotype I (+- - - - + +) (29%), in contrast, among chromosomes with beta(A) the frequency of haplotype I is much greater than that of haplotype II. These data confirm what was found by other authors. Nevertheless, our results disagree with those of previous studies of Sardinians, both in frequencies values and in the numbers of haplotypes identified. Population analysis performed with samples carrying the beta-thalassemic mutation highlighted the peculiarity of Sardinians with respect to other Mediterranean populations. The Corsican population is most similar to the Sardinian population, confirming previous analyses performed with both classical markers and mitochondrial and genomic DNA.

Production of β‐globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous β039 thalassemia patients

“…There are numerous examples of inherited diseases caused by nonsense mutations, such as cystic fibrosis [7,8], lysosomal storage disorders [9], Duchenne muscular dystrophy [10,11], and thalassemia [12,13]. There are also noninherited diseases associated to de novo formation of stop codons.…”

“…As far as thalassemia syndromes, in the b 0 39-thalassemia, the CAG (Gln) codon is mutated to an UAG stop codon [12,13], leading to premature translation termination and to mRNA destabilization through NMD [19,20]. The b 0 39-thalassemia mutation is very frequent in Italy (about 70% of the total b-thalassemia mutations) [21] and, in general, in the whole Mediterranean area.…”

Development of K562 cell clones expressing β‐globin mRNA carrying the β039 thalassaemia mutation for the screening of correctors of stop‐codon mutations

“…For instance, in β 0 39-thalassaemia the CAG (glutamine) codon of the β -globin mRNA is mutated to the UAG stop codon [7,8], leading to premature translation termination and to mRNA destabilization through the well-described NMD (nonsense-mediated mRNA decay) [3,4]. Other examples of stop mutations of the β -globin mRNA occur at positions 15 [9], 37 [10,11] and 127 [12] of the mRNA sequence.…”

A Novel Frameshift Mutation (+A) at Codon 18 of the β-Globin Gene Associated with High Persistence of Fetal Hemoglobin Phenotype and δβ-Thalassemia

“…In contrast to α-thalassemia, where deletions in the α-globin gene cluster account for the disease, the molecular defects causing β-thalassemia are usually point mutations involving only 1 or few nucleotide(s) [4]. For instance, β⁰39-thalassemia is caused by a stop codon mutation that leads to premature termination of β-globin chain synthesis [5]; the β⁰IVSI-1 mutation suppresses correct maturation of the β-globin RNA precursor, while in thalassemia with the β + IVSI-110 mutation normal and abnormal spliced β-globin RNA precursors coexist [6]. …”