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Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree

✍ Scribed by Silverman, Jeremy M.; Greenberg, David A.; Altstiel, Larry D.; Siever, Larry J.; Mohs, Richard C.; Smith, Christopher J.; Zhou, Guilan; Hollander, Tovah E.; Yang, Xin-Ping; Kedache, Medhi; Li, Ge; Zaccario, Michele L.; Davis, Kenneth L.

Publisher: John Wiley and Sons
Year: 1996
Tongue: English
Weight: 44 KB
Volume: 67
Category: Article
ISSN: 0148-7299
DOI: 10.1002/(sici)1096-8628(19960409)67:2<162::aid-ajmg6>3.0.co;2-u

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✦ Synopsis

We attempted to identify a locus for schizophrenia and related disorders in 24 nuclear families of schizophrenic probands using a predefined classification system for affected cases that included those disorders most clearly identified as sharing a genetic relationship with schizophrenia-schizoaffective disorder and schizotypal personality disorder. Initially, we evaluated 8 markers on chromosome 5 on the first 12 families with available genotyping and diagnostic assessments and, assuming autosomal dominant transmission, found a lod score of 2.67 for the D5Slll locus (5~14.1-13.1) in one large nuclear family (no. 17; sibship: n = 12; schizophrenia: n = 3; schizotypal personality disorder: n = 2); the other 11 families were much smaller, less complete, and provided 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 schizophrenia was used to define affectedness, the positive evidence for linkage to D5Slll was greatly reduced. Sensitivity analysis indicated that the lod score is heavily dependent upon the predefined diagnostic criteria. Our studies of other families of schizophrenic probands eventually totalled 23, but linkage to D5Slll in these yielded a -2.41 lod score. The results provide evidence for genetic linkage of the D5Slll locus to schizophrenia and related disorders in one family. It may be of in-

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