THE POLYADENYLATION SITE MUTATION IN THE ALPHA-GLOBIN GENE-CLUSTER
- 1 February 1988
- journal article
- research article
- Vol. 71 (2) , 313-319
Abstract
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 .fwdarw. 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 arise as a result of a recombination between two misaligned chromosomes bearing the .alpha.T Saudi .alpha. defect.This publication has 19 references indexed in Scilit:
- Hemoglobin I Mutation Encoded at Both α-Globin Loci on the Same Chromosome: Concerted Evolution in the Human GenomeScience, 1984
- A technique for radiolabeling DNA restriction endonuclease fragments to high specific activityAnalytical Biochemistry, 1983
- Genetic and molecular diversity in nondeletion Hb H disease.Proceedings of the National Academy of Sciences, 1981
- Mutation in an intervening sequence splice junction in man.Proceedings of the National Academy of Sciences, 1981
- A New Genetic Basis for Hemoglobin-H DiseaseNew England Journal of Medicine, 1980
- The chromosomal arrangement of human α-like globin genes: Sequence homology and α-globin gene deletionsCell, 1980
- Triplicated alpha-globin loci in humans.Proceedings of the National Academy of Sciences, 1980
- The molecular basis of α-thalassemias: Frequent occurrence of dysfunctional α loci among non-Asians with Hb H diseaseCell, 1979
- Identification of a Nondeletion Defect in α-ThalassemiaNew England Journal of Medicine, 1977
- Localization of the human α-globin structural gene to chromosome 16 in somatic cell hybrids by molecular hybridization assayCell, 1977