β-Globin gene inactivation by DNA translocation in γβ-thalassaemi
Abstract
The beta-globin gene present on the deletion locus in a Dutch gamma beta-thalassaemic patient was found to be identical to the normal beta-globin gene with respect to DNA sequence and its transcription in HeLa cells. DNase I sensitivity and methylation experiments show that the affected beta-globin gene is present in an inactive configuration in vivo. This is the result of a translocation of a normally inactive locus next to the beta-globin gene on the affected chromosome, or the deletion of sequences which are normally required for the maintenance of the active state.
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Non-coding enhancer deletions have been linked to severe human disease phenotypes such as beta thalassaemia and polydactyly.
“It soon became clear that enhancers also played vital roles in humans, with non-coding enhancer deletions starting to be linked to severe disease phenotypes such as beta thalassaemia and polydactyly [25–28].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [25]
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- Authors
- Kioussis, D., Vanin, E., deLange, T., Flavell, R. A., & Grosveld, F. G.
- Affiliations
- National Institute for Medical Research (GB)
- Venue
- Nature
- Published
- 1983-12
- Volume
- 306
- Issue
- 5944
- Pages
- 662-666
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2080670274
- Cited by
- 264
- References
- 32
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 11 · 2017: 4 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 6 · 2012: 8
- FWCI
- 7.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- beta-globin gene, gene inactivation, DNA translocation, gene deletion, DNA methylation, DNase I sensitivity, transcription, chromosomal rearrangements, gene silencing
- MeSH terms
- Alleles, Base Sequence, DNA, DNA Restriction Enzymes, Genes, Globins, HeLa Cells, Humans, Methylation, Mutation, Thalassemia, Transcription, Genetic, Translocation, Genetic
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