EVIDENCE OF A LOCUS FOR SCHIZOPHRENIA AND RELATED DISORDERS ON THE SHORT ARM OF CHROMOSOME-5 IN A LARGE PEDIGREE

We attempted to identify a locus for schizophrenia and related disorde rs in 24 nuclear families of schizophrenic probands using a predefined classification system for affected cases that included those disorder s most clearly identified as sharing a genetic relationship with schiz ophrenia-schizoaffective disorder and schizotypal personality disorder . Initially, we evaluated 8 markers on chromosome 5 on the first 12 fa milies with available genotyping and diagnostic assessments and, assum ing autosomal dominant transmission, found a lod score of 2.67 for the D5S111 locus (5p14.1-13.1) in one large nuclear family (no, 17; sibsh ip: n = 12; schizophrenia: n = 3; schizotypal personality disorder: n = 2); the other 11 families were much smaller, less complete, and prov ided little additional information, Other branches of no. 17 were then assessed and the 2-point lod score for family 17 rose to 3.72; using multipoint analysis the lod score in 17 was 4.37. When only schizophre nia was used to define affectedness, the positive evidence for linkage to D5S111 was greatly reduced, Sensitivity analysis indicated that th e lod score is heavily dependent upon the predefined diagnostic criter ia, Our studies of other families of schizophrenic probands eventually totalled 23, but linkage to D5S111 in these yielded a -2.41 lod score , The results provide evidence for genetic linkage of the D5S111 locus to schizophrenia and related disorders in one family, It may be of in terest that over several generations, almost all the ancestors of fami ly 17 could be traced back to a small, relatively isolated, hill regio n of Puerto Rico. (C) 1996 Wiiey-Liss, Inc.