The broad objective of this continuation application is to detect and localize susceptibility loci in bipolar and related affective disorders. This goal will be attained by l. typing 39 extended high-density bipolar pedigrees with polymorphic DNA markers (these are previously ascertained medium-to-large sized kindreds with established cell lines on over 1000 informative members; the planned follow-up- see point 3 - will enlarge the sample to nearly 2000 individuals altogether); 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, and generate, if appropriate, sufficient meiotic events for the cloning procedures. 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 #
2R01MH042535-06A3
Application #
2245469
Study Section
Special Emphasis Panel (ZRG2-MGN (Q1))
Project Start
1987-07-01
Project End
1998-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
6
Fiscal Year
1995
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
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
Baron, M (1997) Genetic linkage and bipolar affective disorder: progress and pitfalls. Mol Psychiatry 2:200-10

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