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.
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