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. 1990 Dec;87(23):9431–9435. doi: 10.1073/pnas.87.23.9431

Inactivation of human alpha-globin gene expression by a de novo deletion located upstream of the alpha-globin gene cluster.

S A Liebhaber 1, E U Griese 1, I Weiss 1, F E Cash 1, H Ayyub 1, D R Higgs 1, J Horst 1
PMCID: PMC55179  PMID: 1701260

Abstract

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.

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