Genetic heterogeneity of "normal" human erythrocyte glucose-6-phosphate dehydrogenase: an isoelectrophoretic polymorphism.

Abstract

Quantitative determination of glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate: NADP+ 1-oxidoreductase, EC 1.1.1.49) activity was carried out in 214 male Nigerian children of 84 mothers with known Gd genotype. The relative intrasibship difference in G6PD activity (normalized to the lowest value within the sibship) was below 0.18 in all cases but one when the children were known to have the same Gd+ allele (identical by descent); whereas it was higher than 0.18 in 18 out of 33 sibships in which children might have had either of the two maternal (electrophoretically identical) Gd+ alleles. G6PD from 10 (8 G6PD B and 2 G6PD A) children belonging to four of the sibships possessing high quantitative variation in G6PD activity was partially purified and extensively characterized. The 8 G6PD type B samples fell unambiguously into two classes on the basis of Km values for glucose 6-phosphate (determined at various pH values), and KCI gradient elution from DEAE-Sephadex columns. The two types of G6PD B were resolved from an artificial mixture on a DEAE-Sephacel column. The two G6PD type A samples were also different from each other by the same criteria. We conclude that "normal" G6PD is genetically heterogeneous and that the structural Gd alleles concerned are all polymorphic in the Nigerian population. In this instance, a human enzyme polymorphism, not associated with enzyme deficiency, is revealed by an approach other than electrophoresis. The electrophoretic analysis of proteins has made it possible to obtain a direct estimate of the variability of primary products of structural genes. However, about two out of three amino acid replacements do not affect the net charge of a protein molecule.

Diagnosis and Treatment of Plasmodium vivax Malaria

“…22 The genetic heterogeneity of phenotypically "normal" G6PD enzyme and varying environmental factors may account for the wide range of activity 10 values. 23 Patients presenting values less than 7 U/gHb are classified as G6PD deficient. G6PD activity is usually defined as a percentage of normal activity, as this provides an intuitive measure of likely vulnerability to hemolytic anemia.…”

A Further Polymorphism of the Gd Locus for Glucose-6-Phosphate Dehydrogenase Present among Blacks (Nigerians) and Apparently Absent among Caucasoids: The Quantitative Isoelectrophoretic Variation of the Gd⁺ Allele

“…The rationale of the present approach to search for a quantitative isoelectropho retic polymorphism of the Gd* gene among Sardinians and Romans was in principle the same as that adopted for Ni gerians [15]. It essentially consisted in comparing the variances found between the G6PD activities of Gd(+) brothers be longing to two sets of couples of brothers: type I = brothers who received Gd* alleles identical by descent (i.e., by the same ma ternal grandparent); type II = brothers who may have, or certainly have received, their Gd* alleles from different maternal grandparents.…”

“…As described in Modiano et al [15]. in thalassacmic individuals can be ascribed solely to their low MCH (for the G6PD in particular see [20], for the red cell en zymes in general sec [21]).…”

“…Moreover, a polymorphism splitting both GdA+ and Gdn into common alleles which, though electrophoretically indistin guishable from each other, were different for a number of structural properties as well as for the associated enzyme activ ities, was described by Modiano et al [15] among Nigerians, but it was not searched for in other races. Thus it seemed interest ing to ascertain whether or not also the quantitative isoelectrophoretic Gd poly morphism is absent among Caucasoids.…”

Estimation of relatedness in natural populations using highly polymorphic genetic markers

“…Several (Dausset, 1958;Vaiman, 1970;Klein, 1987) (Coyne, 1976;Singh et al, 1976;Modiano et al, 1979;Ramshaw et al, 1979;Singh, 1979;Keith, 1983 (Chakraborty et al, 1988), for estimates of relatedness between colonies of social insects (Pamilo and Crozier, 1982;Pamilo, 1984;Queller et al, 1988;Queller and Goodnight, 1989) (Lynch, 1988;Brookfield, 1989; Lewin, 1989 (Lynch, 1988). The expression proposed by Nei and Li (1979) …”