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

Journal Article · Sat Dec 01 00:00:00 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), Vol. 87:23; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

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