In cooperation with the medical genetics program, cytogenetic methods were used to investigate over 200 patients participating in clinical protocols of the various institutes. Studies of Alzheimer's disease and adult Down syndrome patients were completed. The only constitutional variation correlated with dementia was typical trisomy 21. Secondary sex chromosomal aberrations of some experimental and control subjects were correlated with age but not disease. Data from cytological analysis of ribosomal DNA gene activity of the nucleolus-organizing regions (NORs) is being analyzed. A study off the NORs in Down syndrome parents and controls was concluded; NOR variants and duplication (dNOR) were not associated with trisomy 21. NOR activity was not significantly different in control and experimental groups and was not influenced by age and sex. Risk of having a child with Down syndrome could not be determined from NOR analysis. Data from a collaborative study of the fragile X chromosome in 48 schizophrenic males and controls were reported. All affected subjects were fragile X negative; one individual with 47,XYY was found among controls. The fra(X) mutation at Xq27 may not be a major genetic factor in typical schizophrenia; the relationship of schizophrenia to mental disorders observed in some fra(X) carriers remains unexplained. Our studies of recognized syndromes with high-resolution analysis confirmed the association of mental retardation, aniridia, and genitourinary anomalies with deletion of 11p13. No abnormalities were found in familial eosinophilia, familial pheochromocytoma, multiple endocrine neoplasia I, fibrodysplasia ossificans progressiva, McCune-Albright syndrome, Cockayne syndrome with xeroderma pigmentosum, and Beckwith-Wiedemann syndrome. In situ hybridization experiments with high-resolution chromosome preparations and previously localized probes are still in progress, and collaborative work with unmapped DNA sequences is planned.
