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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.

Original publication




Journal article


Proceedings of the National Academy of Sciences of the United States of America

Publication Date





9431 - 9435


Howard Hughes Medical Institute, Department of Human Genetics, University of Pennsylvania, Philadelphia 19104.


Reticulocytes, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 16, Humans, Chromosome Deletion, Globins, DNA, RNA, Restriction Mapping, Cloning, Molecular, Gene Expression Regulation, Genotype, Haplotypes, Genes, Multigene Family, Adult, Female