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2 independent genetic factors in the beta globin gene cluster are associated with high g gamma levels in the hemoglobin of sickle cell anemia patients


, : 2 independent genetic factors in the beta globin gene cluster are associated with high g gamma levels in the hemoglobin of sickle cell anemia patients. Blood 64(2): 452-457

The .gamma.-chains of fetal Hb (HbF) of newborn babies are composed of about 70% G.gamma. and 30% A.gamma. In most babies, the G.gamma. value declines postnatally to 40%, but in about 20% of black SS patients from Georgia [USA] 5 yr and older, the G.gamma. level remains high at 60%. Some 3-4% of black newborns have high G.gamma. values of 85%. PstI digestion of DNA of 1 such high G.gamma. baby and of 1 normal newborn showed the former to be heterozygous for the -G.gamma.-G.gamma.- and -G.gamma.-A.gamma.- chromosomes. Only about 1/4 of high G.gamma. SS patients were such heterozygotes, while 3/4 were -G.gamma.-A.gamma.-/-G.gamma.-A.gamma.- homozygotes. Analysis of DNA of 38 SS patients without the -G.gamma.-G.gamma.- chromosome showed a correlation of G.gamma. values with genotype at 1 polymorphic restriction site: at the HincII site in the .psi.beta. gene, all -G.gamma.-A.gamma.-/-G.gamma.-A.gamma.- homozygotes with high G.gamma. were -/- or +/+, while low G.gamma. individuals were all -/-. Family studies, involving analyses at 4 polymorphic sites (HindIII sites in the G.gamma. and A.gamma. genes and HincII sites in the .psi.beta. gene and 3' to it), suggested the association of an unidentified high G.gamma. genetic determinant with haplotype + - + +. This indicates that a genetic factor causing high G.gamma. levels in SS patients is closely linked to the -G.gamma.-A.gamma.-.psi.beta. region of the .beta.-globin gene cluster.

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