Gene dosage effect in acquired monosomy 7: distinct behaviour of β-glucuronidase and phosphoserine phosphatase.

Evidence for gene dosage effect for β-glucuronidase (GUSB) and phosphoserine phosphatase (PSP), whose genes are mapped on chromosone 7, was searched in a group of 13 patients with myeloproliferative disorders and acquired monosomy 7. The monosomy 7 was the sole anomaly in nine patients and was associated with other chromosome changes in four. A group of 19 patients with similar diseases but with normal karyotype or with anomalies not involving chromosone 7 served as control. β-galactosidase and arylsulphatase A, whose genes are not on chromosome 7, were tested as control enzymes. We obtained evidence for a gene dosage effect for GUSB, but not for PSP. When all cases with monosomy 7 were compared with controls, no dosage effect was observed for PSP, but when this group was split into two, according to the presence of anomalies additional to the monosomy 7, the values of activity in the group with additional anomalies were significantly lower than in the controls. Thus, in the case of PSP, the loss of one allele is not followed immediately by reduction in activity, and this could be due to the specific importance of PSP in nucleic acid metabolism. We postulate that some regulatory mechanisme are able to keep normal levels of PSP even in the presence of only one allele, and that they are overwhelmed only when additional chromosome changes are present. These changes tend to involve chromosomes carrying genes for enzymes involved in a metabolic pathway closely related to PSP functions, and only then is a gene dosage effect for PSP detectable.