The broad objective of this continuation application to detect and localize susceptibility loci in bipolar and related affective disorders. This goal will be attained by 1. typing 50 extended high-density bipolar pedigrees with polymorphic DNA markers (these are 20 previously ascertained medium- to-large sized kindreds with established cell lines on over 1000 informative members and an additional 30 like pedigrees to be collected); marker typing will focus on systematic scan of the genome, including candidate genes, with special emphasis on PCR based technology and microsatellite polymorphisms; 2. performing linkage analysis using a range of phenotypic and genetic models; 3. assessing the impact of diagnostic update and extension of pedigrees on the linkage results (this will be accomplished by a follow-up study of the pedigrees already identified using comprehensive clinical ratings and operational diagnostic criteria). Pending the results of the linkage analyses, long-range goals will include: Identification and characterization of the disease gene(s); definition of linked disease forms on clinical and biological measures; elucidation of gene-environment interaction; and expansion of the pedigree roster to replicate linkage results, assess genetic heterogeneity, an generate, if appropriate, sufficient meiotic events for the cloning procedures. Israel is the data collection site. There are several reasons for this choice: 1. Availability of multigenerational pedigrees with multiple affected cases that are readily accessible for study. 2. Low rates of alcoholism and drug use, conditions that confound the psychiatric diagnosis. 3. An opportunity co compare different populations and cultures. 4. Previous successful collaboration and intriguing findings that require extension. 5. The relatively low cost of human research. israel, probably uniquely, meets all these requirements. The availability of a unique series of pedigrees, coupled with recent advances in diagnostic procedures, molecular genetic techniques, and linkage analysis, holds promise for unraveling the genetic mechanisms that underlie some forms of major affective illness. This, in turn, may have important 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 #
5R01MH043979-07
Application #
2445488
Study Section
Special Emphasis Panel (SRCM (09))
Project Start
1989-02-01
Project End
2000-06-30
Budget Start
1997-07-01
Budget End
2000-06-30
Support Year
7
Fiscal Year
1997
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
Xu, Haiyan; Cheng, Rong; Juo, Suh-Hang et al. (2011) Fine mapping of candidate regions for bipolar disorder provides strong evidence for susceptibility loci on chromosomes 7q. Am J Med Genet B Neuropsychiatr Genet 156:168-76
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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