MAPPING SCHIZOPHRENIA GENES IN DAGHESTANIAN ISOLATES

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DESCRIPTION: (Directly from Abstract): Schizophrenia, which afflicts an estimated 0.5 to 1% of the world's population, is a devastating psychiatric syndrome that causes untold suffering and losses. A notable aspect of the disease is that despite differing cultures and environments of the world, the prevalence and presentation of disease are most noted for being similar. The presentation and course of schizophrenia is no different in Daghestan, Russia, but the population structure of Daghestan presents unique opportunities to explore the genetic etiology of this devastating illness. In particular, a large fraction of its population is rural, living in isolated villages called auls, with substantial intermarriage among members of the same aul. Thus the auls are essentially extended families, with some families have numerous affected individuals and yet the disease is absent in others. This pattern suggests a largely genetic origin of schizophrenia in Daghestan, as is true for other populations around the world. Our principal objective is to identify genes that underlie susceptibility to schizophrenia in the ethnically diverse population of Daghestan. We will ascertain 12 large "schizophrenia" families from primary genetic isolates; each containing a large number of affected individuals. Most of the 12 genetically isolated families will be from the Dargin ethnic group; a large group founded about 2000 years ago. To date, 9 large extended families have been partially ascertained, of which 3 are Dargin families; one Dargin family has 20 cases of schizophrenia, another has 30 and the largest has 60. The three new families, containing at least 10 affected individuals, also will be of Dargin origin. In addition, 100 smaller Dargin families having at least two affected individuals will be ascertained. We will use DNA samples from the large families to perform a genome scan and linkage analyses to detect regions of the genome harboring genes affecting liability to schizophrenia. These regions, called candidate regions, will be evaluated further by genetic and statistical analyses of all DNA samples, with the goal to distinguish between true and false signals from the genome scan and to refine the location of liability genes. Finally genetic and statistical analyses will attempt to define liability genes themselves by evaluating a dense set of markers in a few candidate regions and by close evaluation of genes in those regions plausibly having an impact on schizophrenia.