Abnormal processing of beta-Malay globin RNA.
Hemoglobin Malay (alpha 2 beta 2 19 Asn----Ser) has been observed in a few Malaysian patients with thalassemia intermedia. The beta Malay substitution increases the homology of the cryptic splice site at codons 17/18/19 of the beta-globin gene to the donor consensus splice sequence, suggesting that the beta-thalassemia associated with this mutation may be due to the generation of a new splice site. To test this hypothesis, we constructed a hybrid gene where we replaced part of a normal beta-globin gene with a PCR amplified region of the beta Malay gene. The expression of this mutant gene was studied in a heterologous transient expression system. The data show that nearly 25% of globin mRNA produced by this gene is abnormally spliced at the new splice site, providing a molecular mechanism for the beta-thalassemia associated with the mutation.
Gonzalez-Redondo
J M
JM
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Brickner
H E
HE
Atweh
G F
GF
D001483:Base Sequence; D005784:Gene Amplification; D005914:Globins / Q000235:genetics*; D006367:HeLa Cells; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D013789:Thalassemia / Q000235:genetics*; D014162:Transfection
D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; D005914:Globins