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Synthesis of normal human hemoglobin A, alpha 2 beta 2, is based upon balanced expression of genes in the alpha-globin gene cluster on chromosome 16 and the beta-globin gene cluster on chromosome 11. Full levels of erythroid-specific activation of the beta-globin cluster depend on sequences located at a considerable distance 5' to the beta-globin gene, referred to as the locus-activating or dominant control region. The existence of an analogous element(s) upstream of the alpha-globin cluster has been suggested from observations on naturally occurring deletions and experimental studies. We have identified an individual with alpha-thalassemia in whom structurally normal alpha-globin genes have been inactivated in cis by a discrete de novo 35-kilobase deletion located approximately 30 kilobases 5' from the alpha-globin gene cluster. We conclude that this deletion inactivates expression of the alpha-globin genes by removing one or more of the previously identified upstream regulatory sequences that are critical to expression of the alpha-globin genes.

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

1990

Volume

87

Pages

9431 - 9435

Keywords

Adult *Chromosome Deletion Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 16 Cloning, Molecular DNA/blood/genetics Female *Gene Expression Regulation *Genes, Structural Genotype Globins/*genetics Haplotypes Human *Multigene Family RNA/blood/genetics Restriction Mapping Reticulocytes/metabolism Support, Non-U.S. Gov't