The PI has completed a linkage study of 29 genetic markers in 26 pedigrees of panic disorder and found weak evidence of linkage at two loci: alpha-haptoglobin, LOD score 1.7, recombination fraction 0.0-0.1; and Bf, LOD score 1.5, recombination fraction 0.1-0.2. This proposal will extend the study through the addition of new pedigrees and the use of recombinant DNA probes to analyze both the new families and the noninformative old ones. The molecular genetics will be carried out in Dr. Jeff Murray's laboratory where the PI is currently working. The research plan is the following: I. Collect 5 new multiplex pedigrees per year (5 have already been identified and 3 completed). II. Extract DNA from WBC saved on the original 26 families. III. Analyze the Hp and Bf loci using DNA probes on new families and old ones that were noninformative at these loci. We have a Hp DNA probe in our laboratory and are in the process of obtaining probes to the MHC, where the Bf locus is found. Traditional markers and HLA types will be obtained on the new families as well. IV. If the LOD scores fall below 1.0 at these loci we will obtain a battery of DNA probes so that, as far as possible, one probe on each arm of each chromosome not already tested will be examined. V. If a LOD score exceeds 3.0, establishing linkage, we will obtain any probes available in the genomic region of the positive locus in order to find the closest possible probe to the disease locus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH034728-05
Application #
3375578
Study Section
(PCBB)
Project Start
1987-01-01
Project End
1990-07-31
Budget Start
1989-01-01
Budget End
1990-07-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Logue, Mark W; Bauver, Sarah R; Knowles, James A et al. (2012) Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families. Am J Med Genet B Neuropsychiatr Genet 159B:274-80
Logue, Mark W; Vieland, Veronica J; Goedken, Rhinda J et al. (2003) Bayesian analysis of a previously published genome screen for panic disorder reveals new and compelling evidence for linkage to chromosome 7. Am J Med Genet B Neuropsychiatr Genet 121B:95-9
Crowe, R R; Goedken, R; Samuelson, S et al. (2001) Genomewide survey of panic disorder. Am J Med Genet 105:105-9
Goedken, R; Ludington, E; Crowe, R et al. (2000) Drawbacks of GENEHUNTER for larger pedigrees: application to panic disorder. Am J Med Genet 96:781-3
Wang, Z; Valdes, J; Noyes, R et al. (1998) Possible association of a cholecystokinin promotor polymorphism (CCK-36CT) with panic disorder. Am J Med Genet 81:228-34
Garvey, M J; Crowe, R R; Wang, Z (1998) An association of NAG levels and a mutation of the CCK gene in panic disorder patients. Psychiatry Res 80:149-53
Crowe, R R; Wang, Z; Noyes Jr, R et al. (1997) Candidate gene study of eight GABAA receptor subunits in panic disorder. Am J Psychiatry 154:1096-100
Kato, T; Wang, Z W; Zoega, T et al. (1996) Missense mutation of the cholecystokinin B receptor gene: lack of association with panic disorder. Am J Med Genet 67:401-5
Schmidt, S M; Zoega, T; Crowe, R R (1993) Excluding linkage between panic disorder and the gamma-aminobutyric acid beta 1 receptor locus in five Icelandic pedigrees. Acta Psychiatr Scand 88:225-8
Wang, Z W; Crowe, R R; Noyes Jr, R (1992) Adrenergic receptor genes as candidate genes for panic disorder: a linkage study. Am J Psychiatry 149:470-4

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