Inactivation of human alpha-globin gene expression by a de novo deletion located upstream of the alpha-globin gene cluster
| Autor: | Stephen A. Liebhaber, F E Cash, I M Weiss, D. R. Higgs, J Horst, H Ayyub, E U Griese |
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| Jazyk: | angličtina |
| Rok vydání: | 1990 |
| Předmět: |
Adult
Reticulocytes Genotype Restriction Mapping Gene mutation Biology Gene mapping hemic and lymphatic diseases Gene expression Gene cluster Humans Globin Cloning Molecular Gene Genetics Regulation of gene expression Multidisciplinary Chromosomes Human Pair 11 DNA Molecular biology Globins Gene Expression Regulation Genes Haplotypes Regulatory sequence Multigene Family RNA Female Chromosome Deletion Chromosomes Human Pair 16 Research Article |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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