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.
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