A nucleotide change at a splice junction in the human β-globin gene is associated with β 0-thalassemia

M. Baird, C. Driscoll, H. Schreiner, G. V. Sciarratta, G. Sansone, G. Niazi, F. Ramirez, A. Bank

Research output: Contribution to journalArticle

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Abstract

β 0-thalassemia is a heterogeneous group of disorders associated with absence of β-globin. In a survey of DNAs from patients with β 0-thalassemia of diverse ethnic origins, a change at the splice junction at the 5' end ot the large intervening sequence (IVS 2) of the human β-globin gene has been found in one patient of Italian and another two of Iranian ethnic origins. The enzyme Hph I recognizes a change at this site and generates a larger-than-normal fragment of DNA, which hybridizes specifically to a β-globin IVS 2 probe. No other changes in β-globin gene DNA structure or organization are detectable by extensive restriction endonuclease analysis. The enzyme HinfI which recognizes a sequence beginning three nucleotides from the 5' end of the IVS 2 splice junction, produces normal fragments and localizes the defect to a G-G-T sequence at the 5'-end IVS 2 splice junction. This sequence is known to be remarkably conserved in all globin genes from many species and in most other genes examined to date. Thus, in at least some β 0-thalassemia patients, the β 0-thalassemia defect is associated with a nucleotide change at a splice junction. These patients provide unique examples of naturally occurring defects in splice junctions of eukaryotic genes associated with absence of specific gene function.

Original languageEnglish (US)
Pages (from-to)4218-4221
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume78
Issue number7 I
DOIs
StatePublished - 1981
Externally publishedYes

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Thalassemia
Globins
Nucleotides
Genes
DNA
DNA Restriction Enzymes
Enzymes
Introns

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A nucleotide change at a splice junction in the human β-globin gene is associated with β 0-thalassemia. / Baird, M.; Driscoll, C.; Schreiner, H.; Sciarratta, G. V.; Sansone, G.; Niazi, G.; Ramirez, F.; Bank, A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 78, No. 7 I, 1981, p. 4218-4221.

Research output: Contribution to journalArticle

Baird, M. ; Driscoll, C. ; Schreiner, H. ; Sciarratta, G. V. ; Sansone, G. ; Niazi, G. ; Ramirez, F. ; Bank, A. / A nucleotide change at a splice junction in the human β-globin gene is associated with β 0-thalassemia. In: Proceedings of the National Academy of Sciences of the United States of America. 1981 ; Vol. 78, No. 7 I. pp. 4218-4221.
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AU - Niazi, G.

AU - Ramirez, F.

AU - Bank, A.

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AB - β 0-thalassemia is a heterogeneous group of disorders associated with absence of β-globin. In a survey of DNAs from patients with β 0-thalassemia of diverse ethnic origins, a change at the splice junction at the 5' end ot the large intervening sequence (IVS 2) of the human β-globin gene has been found in one patient of Italian and another two of Iranian ethnic origins. The enzyme Hph I recognizes a change at this site and generates a larger-than-normal fragment of DNA, which hybridizes specifically to a β-globin IVS 2 probe. No other changes in β-globin gene DNA structure or organization are detectable by extensive restriction endonuclease analysis. The enzyme HinfI which recognizes a sequence beginning three nucleotides from the 5' end of the IVS 2 splice junction, produces normal fragments and localizes the defect to a G-G-T sequence at the 5'-end IVS 2 splice junction. This sequence is known to be remarkably conserved in all globin genes from many species and in most other genes examined to date. Thus, in at least some β 0-thalassemia patients, the β 0-thalassemia defect is associated with a nucleotide change at a splice junction. These patients provide unique examples of naturally occurring defects in splice junctions of eukaryotic genes associated with absence of specific gene function.

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