The polyadenylation site mutation in the alpha-globin gene cluster.
In a previous study, we described a form of nondeletion alpha-thalassemia (alpha T Saudi alpha) found in subjects of Saudi Arabian origin. In the current study, using synthetic oligoprobe hybridization and restriction enzyme analysis, we have demonstrated that the molecular basis of alpha T Saudi alpha is due solely to a single base mutation (AATAAA----AATAAG) in the polyadenylation signal of the alpha 2 gene and that the frameshift mutation in codon 14 of the linked alpha 1 gene is the result of a cloning artefact. The alpha 2 polyadenylation signal mutation occurs in other Middle Eastern and the Mediterranean populations and is responsible for the clinical phenotype of Hb H disease in some Saudi Arabian individuals with five alpha genes (alpha T Saudi alpha/(alpha alpha alpha)T Saudi). Evidence suggests that the (alpha alpha alpha)T Saudi haplotype has arisen as a result of a recombination between two misaligned chromosomes bearing the alpha T Saudi alpha defect.
Thein
S L
SL
Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Headington, England.
Wallace
R B
RB
Pressley
L
L
Clegg
J B
JB
Weatherall
D J
DJ
Higgs
D R
DR
D000483:Alleles; D005787:Gene Frequency; D005914:Globins / Q000235:genetics*; D006447:Hemoglobin H; D006801:Humans; D007557:Israel / Q000208:ethnology; D005810:Multigene Family; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D010375:Pedigree; D011061:Poly A / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012529:Saudi Arabia / Q000208:ethnology; D013789:Thalassemia / Q000235:genetics*
D009838:Oligodeoxyribonucleotides; D011061:Poly A; D005914:Globins; D006447:Hemoglobin H