Somatic-cell selection is a major determinant of the blood-cell phenotype in heterozygotes for glucose-6-phosphate dehydrogenase mutations causing severe enzyme deficiency
- Istituto Internazionale di Genetica e Biofisica, Naples (Italy); and others
X-chromosome inactivation in mammals is regarded as an essentially random process, but the resulting somatic-cell mosaicism creates the opportunity for cell selection. In most people with red-blood-cell glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme-deficient phenotype is only moderately expressed in nucleated cells. However, in a small subset of hemizygous males who suffer from chronic nonspherocytic hemolytic anemia, the underlying mutations (designated class I) cause more-severe G6PD deficiency, and this might provide an opportunity for selection in heterozygous females during development. In order to test this possibility we have analyzed four heterozygotes for class I G6PD mutations: two with G6PD Portici (1178G{r_arrow}A) and two with G6PD Bari (1187C{r_arrow}T). We found that in fractionated blood cell types (including erythroid, myeloid, and lymphoid cell lineages) there was a significant excess of G6PD-normal cells. The significant concordance that we have observed in the degree of imbalance in the different blood-cell lineages indicates that a selective mechanism is likely to operate at the level of pluripotent blood stem cells. Thus, it appears that severe G6PD deficiency affects adversely the proliferation or the survival of nucleated blood cells and that this phenotypic characteristic is critical during hematopoiesis. 65 refs., 6 figs., 3 tabs.
- OSTI ID:
- 476760
- Journal Information:
- American Journal of Human Genetics, Vol. 59, Issue 4; Other Information: PBD: Oct 1996
- Country of Publication:
- United States
- Language:
- English
Similar Records
Ionizing Particle Radiation as a Modulator of Endogenous Bone Marrow Cell Reprogramming: Implications for Hematological Cancers [Ionizing radiation as a modulator of bone marrow cell reprogramming: low doses as a driver for associated hematological cancers]
The frequency among Japanese of heterozygotes for deficiency variants of 11 enzymes
Related Subjects
BASIC STUDIES
PATIENTS
PHENOTYPE
METABOLIC DISEASES
HEMIC DISEASES
ANEMIAS
HUMAN X CHROMOSOME
MOSAICISM
GENETIC MAPPING
OXIDOREDUCTASES
ENZYME ACTIVITY
BLOOD CELLS
CELL PROLIFERATION
GENES
SOMATIC MUTATIONS
GENE MUTATIONS
GENE REGULATION
GLUCOSE
AMINO ACIDS
BLOOD FORMATION
STEM CELLS
POLYMERASE CHAIN REACTION