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The β 0 ‐thalassemia in an American black family is due to a single nucleotide substitution in the acceptor splice junction of the second intervening sequence
Author(s) -
Padanilam B. J.,
Huisman T. H. J.
Publication year - 1986
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830220306
Subject(s) - microbiology and biotechnology , restriction enzyme , nucleotide , splice , rna splicing , biology , gene , genetics , southern blot , rna
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‐β 0 ‐thalassemia failed to detect any deletion in the β 0 ‐globin gene region, but cloning and sequencing of the β 0 ‐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.