Combinations of hemoglobin G,hemoglobin S and thalassemia occurring in one family

1. A Caucasian family is described in which, on the basis of clinical, hematologic and biochemical findings, it is postulated that the genes responsible forhemoglobins S and G and for the thalassemia defect are present.

2. On the basis of the study of this family, it is concluded that:

a. The genes responsible for hemoglobins G and S cannot be alleles.

b. The genes responsible for hemoglobin G and thalassemia cannot be alleles.

c. The absence of hemoglobin A in individuals heterozygous for two "hemoglobin genes" does not provide critical evidence concerning the allelic relations ofsuch genes.

d. In this family, heterozygosity for the gene responsible for hemoglobin Gresults in an asymptomatic trait condition, in which some 40% of the hemoglobinis abnormal. When the gene responsible for G is combined with a hemoglobin Sgene or a thalassemia gene, or both, the presence of hemoglobin G does not significantly alter the expression of these genes on their combinations. For example,an individual of the phenotype SG, whose hemoglobin contained no demonstrableA, was clinically a sickle cell trait, in that he showed no evidence of physiologichandicap.

e. Individuals heterozygous for both the G and thalassemia genes may showon electrophoresis only hemoglobin G. This illustrates the unreliability in somecases of diagnosing genotype on the basis of electrophoretic findings.

f. On the basis of these findings, hemoglobin G should probably be regardedas a normal variant of hemoglobin rather than as an abnormal type of hemoglobin.

Submitted on August 4, 1956 Accepted on September 15, 1956