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

Journal Article · Fri Nov 30 23:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.23.9431· OSTI ID:5014705

Liebhaber, S A; Weiss, I; Cash, F E ^[1]; Griese, E U; Horst, J ^[2]; Ayyub, H; Higgs, D R ^[3]

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1. Univ. of Pennsylvania, Philadelphia (United States)
2. Univ. of Muenster (West Germany)
3. John Radcliffe Hospital, Oxford (England)

Synthesis of normal human hemoglobin A, {alpha}{sub 2}{beta}{sub 2}, is based upon balanced expression of genes in the {alpha}-globin gene cluster on chromosome 15 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{prime} 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. The authors 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{prime} from the {alpha}-globin gene cluster. They 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.

• OSTI ID: 5014705
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:23; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550401* -- Genetics-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANEMIAS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOSYNTHESIS
CARBOXYLIC ACIDS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DISEASES
DNA HYBRIDIZATION
GENE MUTATIONS
GENE REGULATION
GENES
GENETIC MAPPING
GLOBINS
HEMIC DISEASES
HEMOGLOBIN
HEREDITARY DISEASES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYBRIDIZATION
INACTIVATION
ISOTOPES
LIGHT NUCLEI
MAPPING
MESSENGER-RNA
MUTATIONS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PIGMENTS
PORPHYRINS
PROTEINS
RADIOISOTOPES
RNA
SYMPTOMS
SYNTHESIS
THALASSEMIA