Structural analysis of the 5 prime flanking region of the. beta. -globin gene in African sickle cell anemia patients: Further evidence for three origins of the sickle cell mutation in Africa

Journal Article · Wed Jun 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.12.4431· OSTI ID:5412140

Chebloune, Y; Pagnier, J; Trabuchet, G; Faure, C; Verdier, G; Labie, D; Nigon, V ^[1]

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1. Universite Claude Bernard-Lyon, Villeurbane (France)

Haplotype analysis of the {beta}-globin gene cluster shows two regions of DNA characterized by nonrandom association of restriction site polymorphisms. These regions are separated by a variable segment containing the repeated sequences (ATTTT){sub n} and (AT){sub x}T{sub y}, which might be involved in recombinational events. Studies of haplotypes linked to the sickle cell gene in Africa provide strong argument for three origins of the mutation: Benin, Senegal, and the Central African Republic. The structure of the variable segment in the three African populations was studied by S1 nuclease mapping of genomic DNA, which allows a comparison of several samples. A 1080-base-pair DNA segment was sequenced for one sample from each population. S1 nuclease mapping confirmed the homogeneity of each population with regard to both (ATTTT){sub n} and (AT){sub x}T{sub y} repeats. The authors found three additional structures for (AT){sub x}T{sub y} correlating with the geographic origin of the patients. Ten other nucleotide positions, 5{prime} and 3{prime} to the (AT){sub x}T{sub y} copies, were found to be variable when compared to homologous sequences from human and monkey DNAs. These results allow us to propose an evolutionary scheme for the polymorphisms in the 5{prime} flanking region of the {beta}-globin gene. The results strongly support the hypothesis of three origins for the sickle mutation in Africa.

• OSTI ID: 5412140
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:12; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENES
MOLECULAR STRUCTURE
RFLPS
BIOLOGICAL EVOLUTION
SICKLE CELL ANEMIA
GENETICS
BENIN
CENTRAL AFRICAN REPUBLIC
DNA
DNA SEQUENCING
GLOBIN
HUMAN POPULATIONS
MUTATIONS
NUCLEASES
PATIENTS
PHOSPHORUS 32
SENEGAL
AFRICA
ANEMIAS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGY
DAYS LIVING RADIOISOTOPES
DEVELOPING COUNTRIES
DISEASES
ENZYMES
ESTERASES
HEMIC DISEASES
HYDROLASES
ISOTOPES
LIGHT NUCLEI
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHODIESTERASES
PHOSPHORUS ISOTOPES
POPULATIONS
RADIOISOTOPES
STRUCTURAL CHEMICAL ANALYSIS
SYMPTOMS
550401* - Genetics- Tracer Techniques