The heterogeneity of the gamma-chain of fetal hemoglobin in HbS heterozygotes.
The relative quantities of the three types of gamma chain (G gamma, A gamma I, A gamma T) were determined in 18 AS parents of selected SS patients, in 15 additional HbS heterozygotes, as well as in additional SS patients, and in 35 SS and 24 AS newborn babies. The low amount of HbF in all AS adults (less than 1%) made it necessary to further improve the isolation procedure of HbF, which was accomplished by introducing an HPL chromatographic method. The additional data for older SS patients confirmed the existence of two groups characterized by either low G gamma (40%) or high G gamma (60%) values in their HbF. A distinction into "high G gamma" and "low G gamma" producers could also be made for HbS heterozygotes. Family studies, however, make it unlikely that the "high G gamma" condition is inherited in a simple mendelian fashion assuming a change in a regulatory mechanism. The presence of the A gamma T mutation, occurring either in cis or in trans to the beta S mutation, has been used to evaluate the possible contribution by specific gamma-chain genes to the gamma-chain composition of the HbF of adult AS persons. No clear pattern because evident, suggesting that most of the gamma-chain of this small amount of HbF could originate from gamma-chain genes in cis or in trans to the beta S gene or from both sets of genes. It is speculated that heterogeneity among "F-cells" may be a primary cause of the observed differences in gamma-chain composition of HbF in HbS heterozygotes.
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000235:genetics; D002648:Child; D005319:Fetal Hemoglobin / Q000235:genetics / Q000302:isolation & purification; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006579:Heterozygote; D006801:Humans
D006451:Hemoglobin, Sickle; D005319:Fetal Hemoglobin