This is an application for an ADAMHA SDAC for additional research training in the area of modern genetic methods and their use in unraveling the genetic basis of anxiety disorders. The objective of the training plan is to provide education and experience in current techniques and applications in molecular genetics and quantitative genetics. This training will be advanced through a research program investigating genetic factors in anxiety disorders using linkage and association studies. The career development plan provides for collection of DNA from members of kindreds where panic disorder appears to be inherited; collection of DNA from unrelated individuals with panic disorder and other anxiety disorders; linkage studies with the panic disorder pedigrees, using restriction fragment length polymorphism (RFLP), polymerase chain reaction (PCR), and denaturing gradient electrophoresis (DGE) techniques; and association studies using those same techniques with candidate genes in individuals with panic disorder and other anxiety disorders. Comparable skills will also be developed through continued fine structure mapping of loci on chromosome 11q (near DRD2 dopamine receptor). Other laboratory techniques are expected to evolve over the five year course of the project and these will be employed whenever appropriate; applying state-of-the-art techniques is a core purpose. The plan also provides for intensive training in computer analysis of these data as they are accumulated, research into improved methods of data analysis, and for tutorial and formal didactic training in theoretical aspects of quantitative genetics. The ultimate scientific objective is to locate a gene important in conferring susceptibility to panic disorder (through linkage or association studies) or to generalized anxiety disorder or post traumatic stress disorder (through association studies focussing on candidate genes), and to map genes potentially important in psychiatry; the ultimate career development objective is to fully train a psychiatrist in human genetics. The preceptor for this project is Dr. Kenneth K. Kidd, who is unusually well qualified to supervise the kind of comprehensive training in methods in linkage and quantitative genetics (as applied to psychiatry) described here.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Unknown (K20)
Project #
5K20MH000931-03
Application #
3088924
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1991-09-30
Project End
1996-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Gelernter, J; Cubells, J F; Kidd, J R et al. (1999) Population studies of polymorphisms of the serotonin transporter protein gene. Am J Med Genet 88:61-6
Gelernter, J; Kranzler, H; Satel, S L (1999) No association between D2 dopamine receptor (DRD2) alleles or haplotypes and cocaine dependence or severity of cocaine dependence in European- and African-Americans. Biol Psychiatry 45:340-5
Gelernter, J; Kranzler, H; Coccaro, E F et al. (1998) Serotonin transporter protein gene polymorphism and personality measures in African American and European American subjects. Am J Psychiatry 155:1332-8
Gelernter, J; Kranzler, H; Lacobelle, J (1998) Population studies of polymorphisms at loci of neuropsychiatric interest (tryptophan hydroxylase (TPH), dopamine transporter protein (SLC6A3), D3 dopamine receptor (DRD3), apolipoprotein E (APOE), mu opioid receptor (OPRM1), and ciliary neurotrophic facto Genomics 52:289-97
Cubells, J F; van Kammen, D P; Kelley, M E et al. (1998) Dopamine beta-hydroxylase: two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation. Hum Genet 102:533-40
Bonvicini, K A (1998) The art of recruitment: the foundation of family and linkage studies of psychiatric illness. Fam Process 37:153-65
Gelernter, J; Van Dyck, C; van Kammen, D P et al. (1997) Ciliary neurotrophic factor null allele frequencies in schizophrenia, affective disorders, and Alzheimer's disease. Am J Med Genet 74:497-500
Cubells, J F; Kobayashi, K; Nagatsu, T et al. (1997) Population genetics of a functional variant of the dopamine beta-hydroxylase gene (DBH). Am J Med Genet 74:374-9
Gelernter, J; Kranzler, H; Coccaro, E et al. (1997) D4 dopamine-receptor (DRD4) alleles and novelty seeking in substance-dependent, personality-disorder, and control subjects. Am J Hum Genet 61:1144-52
Gelernter, J; Kranzler, H; Cubells, J F (1997) Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects. Hum Genet 101:243-6

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