β-Globin-like Gene Cluster Haplotypes in Hemoglobinopathies

  • Shanmugakonar Muralitharan
  • Rajagopal Krishnamoorthy
  • Ronald L. Nagel
Part of the Methods in Molecular Biology™ book series (MIMM, volume 82)


The pioneering work of Kan and Dozy (1) revealed by restriction endonuclease mapping a genetic variation in an HpaI recognition site about 5000 nucleotides from the 3′ end of the β-globin gene. Instead of a normal 7.6-kb fragment containing the β-globin gene, 7.0- and 13.0-kb variants were detected and were found in African Americans, Asians, and Caucasians. The 13.0-kb variant (HpaI+) was frequently associated with the sickle hemoglobin (Hb) mutation. Kan and Dozy (1) predicted that polymorphisms in a restriction enzyme site could be considered a new class of genetic marker and may offer a new approach to linkage analysis and anthropological studies. Based on limited data (2), they reported that linkage to the wild-type HpaI-positive site was characteristic of West Africans while an HpaI-negative site typified East Africans. This finding did not show definitively that the mutation had occurred in two different chromosomal backgrounds, because a secondary mutation at the HpaI site could have postdated the sickle mutation.


Polymerase Chain Reaction Reaction Major Haplotype Polymerase Chain Reaction Cycling Condition Thalassemic Mutation XmnI Polymorphism 
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Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Shanmugakonar Muralitharan
    • 1
  • Rajagopal Krishnamoorthy
    • 2
  • Ronald L. Nagel
    • 3
    • 4
  1. 1.Department of MedicineAlbert Einstein College of MedicineBronx
  2. 2.INSERM U468Hôpital Robert DebrùParisFrance
  3. 3.Division of Hematology, Department of MedicineAlbert Einstein College of MedicineBronx
  4. 4.Department of Physiology and BiophysicsAlbert Einstein College of MedicineBronx

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