Using molecular genetic techniques, the chief objectives of this proposal are to home in on the disease gene in X-linked bipolar affective illness and to detect other major genes in the transmission of the disorder. These goals will be attained by 1. gene mapping and related DNA techniques; and 2. conducting linkage studies with DNA markers in suitable pedigrees segregating bipolar and related affective disorders. The study will also aim to characterize linked vs. unlinked cases on clinical measures in an attempt to identify and define homogeneous subsets of the disorder and to compare different populations and ethnic groups for possible genetic differences. Long-term goals will include cloning of the defective genes; determination of their structure; searching for their biological products; and assessment o( gene-environment interaction. Israel is the data collection site. There are six main reasons for this choice: 1. X-linked pedigrees have already been identified. 2. Availability of large multigenerational pedigrees with multiple affected cases that are readily accessible for study. 3. Low rates of alcoholism and drug use, conditions that confound the psychiatric diagnosis. 4. An opportunity to compare different populations and culture. 5. Previous successful collaboration and intriguing findings that require extension. 6. The relatively low cost of human research. Israel, probably uniquely, meets all these requirements. The availability of a unique population, coupled with recent methodological advances such as molecule genetic techniques, approaches to systematically obtaining family data, structured interviews, precise diagnostic criteria with improved reliability; and a range of genetic models, holds much promise for unraveling the genetic mechanisms that underlie affective illness. This, in turn, could have major implications for the etiology, nosology, pathophysiology and, possibly, prevention and treatment of these disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH043979-03
Application #
3383448
Study Section
Psychopathology and Clinical Biology Research Review Committee (PCB)
Project Start
1989-02-01
Project End
1993-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
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Park, N; Juo, S H; Cheng, R et al. (2004) Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia. Mol Psychiatry 9:1091-9
Segurado, Ricardo; Detera-Wadleigh, Sevilla D; Levinson, Douglas F et al. (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder. Am J Hum Genet 73:49-62
Liu, J; Juo, S H; Dewan, A et al. (2003) Evidence for a putative bipolar disorder locus on 2p13-16 and other potential loci on 4q31, 7q34, 8q13, 9q31, 10q21-24, 13q32, 14q21 and 17q11-12. Mol Psychiatry 8:333-42
Baron, M (2001) Genetic linkage and bipolar disorder: a cautionary note. J Affect Disord 67:267-73
Liu, J; Juo, S H; Terwilliger, J D et al. (2001) A follow-up linkage study supports evidence for a bipolar affective disorder locus on chromosome 21q22. Am J Med Genet 105:189-94
Aita, V M; Liu, J; Knowles, J A et al. (1999) A comprehensive linkage analysis of chromosome 21q22 supports prior evidence for a putative bipolar affective disorder locus. Am J Hum Genet 64:210-7
Gecz, J; Barnett, S; Liu, J et al. (1999) Characterization of the human glutamate receptor subunit 3 gene (GRIA3), a candidate for bipolar disorder and nonspecific X-linked mental retardation. Genomics 62:356-68
Knowles, J A; Rao, P A; Cox-Matise, T et al. (1998) No evidence for significant linkage between bipolar affective disorder and chromosome 18 pericentromeric markers in a large series of multiplex extended pedigrees. Am J Hum Genet 62:916-24
Baron, M (1997) Genes and manic depression. Psychiatr Genet 7:49-51

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