The long-term objective of this proposal is the identification of genes contributing to schizophrenia susceptibility. The investigators propose to first identify the genomic regions which may harbor such genes by performing linkage studies in genetically isolated populations (populations that originated from a small number of founders and expanded in relative isolation). To this end, the investigators have collected families afflicted with schizophrenia from genetically isolated founder populations with accessible genealogy that differ in their demographic characteristics (sample size, growth rate) as well in their age of ancestry. Specifically, they have collected families from the island populations of Kosrae and Yap in Micronesia (genetic isolates of recent origin), and the Afrikaners in South Africa (genetic isolate of 'older' origin). All three sites offer excellent genealogical data that could significantly improve the ability to assess the evidence for increased allele or segment sharing among affected individuals by taking into account all known genealogical relationships. The investigators propose to perform a 10-cM genome-wide scan in the families they have collected and examine all 'candidate regions' identified through the 10-cM scan by denser marker coverage and construction of haplotypes. The identification of genes that increase susceptibility to schizophrenia is expected to have a major impact on the understanding of disease pathogenesis and, ultimately, lead to the development of new, less empirical therapies.
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