A family was studied in which two inherited defects of the non-alpha-globin cluster segregate: Greek hereditary persistence of fetal hemoglobin (HPFH) and beta-thalassemia. Fragments of the non-alpha-globin cluster from two patients were cloned in cosmid and phage lambda vectors, and assigned to either the HPFH or beta-thalassemic chromosome on the basis of the demonstration of a polymorphic BglII site in the HPFH gamma-globin cluster. The thalassemic beta-globin gene carries a mutation at nucleotide 1 of the intervening sequence I, known to cause beta zero-thalassemia; the beta-globin gene from the HPFH chromosome is entirely normal, both in the intron-exon sequence and in 5' flanking regions required for transcription. As the compound HPFH/beta-thalassemia heterozygote synthesizes HbA, these data prove that the HPFH beta-globin gene is functional, although at a decreased rate; its lower activity is likely to be due to a distant mutation. The HPFH A gamma-globin gene shows only two mutations: a T----C substitution in the large intervening sequence (responsible for the BglII polymorphic site) and a C----T substitution 196 nucleotides 5' to the cap site; the 5' flanking sequence is normal up to -1350 nucleotides upstream from the gene. Circumstantial evidence suggests that the mutation at -196 may be responsible for the abnormally high expression of the A gamma-globin gene.
A molecular study of a family with Greek hereditary persistence of fetal hemoglobin and beta-thalassemia / B. Giglioni, C. Casini, R. Mantovani, S. Merli, P. Comi, S. Ottolenghi, G. Saglio, C. Camaschella, U. Mazza. - In: EMBO JOURNAL. - ISSN 0261-4189. - 3:11(1984 Nov), pp. 2641-2645.
|Titolo:||A molecular study of a family with Greek hereditary persistence of fetal hemoglobin and beta-thalassemia|
|Parole Chiave:||Base Sequence; Cloning, Molecular; DNA Restriction Enzymes; Fetal Hemoglobin; Genes; Greece; Humans; Nucleic Acid Hybridization; Plasmids; Polymorphism, Genetic; Thalassemia|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
|Data di pubblicazione:||nov-1984|
|Appare nelle tipologie:||01 - Articolo su periodico|