Schizophrenia is considered a complex genetic disorder with no clear Medelian pattern of inheritance. Markers for a genetic locus have not been identified in consistently replicated studies using standard lod score analyses; however, thus far, no one has yet attempted to use the sib-pair approach to screen the genome in schizophrenia. Molecular genetic screening of a moderate number of sibling pairs, has been successful in finding markers linked to at least one other complex genetic disorder, diabetes, and several confirmed linkages using standard approaches have been successful in identifying chromosomal regions for other neuropsychiatric disorders, such as Alzheimer s disease. Over the past seven years the present investigators have identified over 400 families in the United States, a catchment area of Northwest London, UK, and a region of Northern Italy, with multiple ill members with DSM-III-R schizophrenia or schizoaffective disorder. Thus far, approximately 235 of these families (comprising 319 sib-pairs) have lymphoblastoid cell lines maintained in culture for continual DNA studies. An additional 33 families have DNA available from whole blood. This project is presently focusing its laboratory approach on a systematic genomic search of all chromosomes in the same families to establish (by sib-pair analyses) whether more than one locus is involved in the genetics of schizophrenia. In addition, other work simultaneously pursued includes continuing to examine the hypothesis that an X/Y homologous gene is a candidate for schizophrenia, and that unstable repeat sequences may identify a candidate locus. These different approaches are being carried out in separate laboratory facilities, but communication and cooperation between collaborators is directed by the PI s of the project. The present proposal is thus for the extension of the collection of the pedigrees with ill sib-pairs (150 new), and follow-up clinical evaluations for the application of molecular genetic techniques to the screening of DNA from this set of families. The funding will be directed toward maintaining the quality of the clinical sample. It is hoped that this valuable clinical cohort will be an important resource in future laboratory searches for gene(s) for schizophrenia.
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