The β0‐thalassemia in an American black family is due to a single nucleotide substitution in the acceptor splice junction of the second intervening sequence

B. J. Padanilam, T. H.J. Huisman

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

An AG dinucleotide is an invariant feature of all acceptor splice sites, and deletion or substitution of (one of) these nucleotides will result in abnormal processing of the β‐globin mRNA. Restriction endonuclease mapping of DNA from an American black patient with Hb S‐β0‐thalassemia failed to detect any deletion in the β0‐globin gene region, but cloning and sequencing of the β0‐globin gene showed a point mutation (A → C) in the highly conserved dinucleotide AG of the acceptor splice junction of the IVS‐2. Blot hybridization analysis of RNA prepared from the erythroid cells of the patient showed only RNA of normal size. The patient and her daughter, who has the same condition, have high levels of Hb F (27%–35%); the mechanism responsible for the greatly increased γ chain production remains unclear.

Original languageEnglish (US)
Pages (from-to)259-263
Number of pages5
JournalAmerican Journal of Hematology
Volume22
Issue number3
DOIs
StatePublished - Jul 1986

Fingerprint

Introns
Nucleotides
RNA
Restriction Mapping
Erythroid Cells
RNA Splice Sites
Globins
Nuclear Family
Point Mutation
Genes
Organism Cloning
Messenger RNA
DNA

Keywords

  • DNA cloning
  • DNA sequencing
  • Hb F
  • S‐β‐thalassemia
  • nucleotide substitution
  • splice site
  • γ level

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "The β0‐thalassemia in an American black family is due to a single nucleotide substitution in the acceptor splice junction of the second intervening sequence",
abstract = "An AG dinucleotide is an invariant feature of all acceptor splice sites, and deletion or substitution of (one of) these nucleotides will result in abnormal processing of the β‐globin mRNA. Restriction endonuclease mapping of DNA from an American black patient with Hb S‐β0‐thalassemia failed to detect any deletion in the β0‐globin gene region, but cloning and sequencing of the β0‐globin gene showed a point mutation (A → C) in the highly conserved dinucleotide AG of the acceptor splice junction of the IVS‐2. Blot hybridization analysis of RNA prepared from the erythroid cells of the patient showed only RNA of normal size. The patient and her daughter, who has the same condition, have high levels of Hb F (27{\%}–35{\%}); the mechanism responsible for the greatly increased γ chain production remains unclear.",
keywords = "DNA cloning, DNA sequencing, Hb F, S‐β‐thalassemia, nucleotide substitution, splice site, γ level",
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AU - Padanilam, B. J.

AU - Huisman, T. H.J.

PY - 1986/7

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N2 - An AG dinucleotide is an invariant feature of all acceptor splice sites, and deletion or substitution of (one of) these nucleotides will result in abnormal processing of the β‐globin mRNA. Restriction endonuclease mapping of DNA from an American black patient with Hb S‐β0‐thalassemia failed to detect any deletion in the β0‐globin gene region, but cloning and sequencing of the β0‐globin gene showed a point mutation (A → C) in the highly conserved dinucleotide AG of the acceptor splice junction of the IVS‐2. Blot hybridization analysis of RNA prepared from the erythroid cells of the patient showed only RNA of normal size. The patient and her daughter, who has the same condition, have high levels of Hb F (27%–35%); the mechanism responsible for the greatly increased γ chain production remains unclear.

AB - An AG dinucleotide is an invariant feature of all acceptor splice sites, and deletion or substitution of (one of) these nucleotides will result in abnormal processing of the β‐globin mRNA. Restriction endonuclease mapping of DNA from an American black patient with Hb S‐β0‐thalassemia failed to detect any deletion in the β0‐globin gene region, but cloning and sequencing of the β0‐globin gene showed a point mutation (A → C) in the highly conserved dinucleotide AG of the acceptor splice junction of the IVS‐2. Blot hybridization analysis of RNA prepared from the erythroid cells of the patient showed only RNA of normal size. The patient and her daughter, who has the same condition, have high levels of Hb F (27%–35%); the mechanism responsible for the greatly increased γ chain production remains unclear.

KW - DNA cloning

KW - DNA sequencing

KW - Hb F

KW - S‐β‐thalassemia

KW - nucleotide substitution

KW - splice site

KW - γ level

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