Dr. Brownstein and his coworkers in the NHGRI continue to study the genetic basis of familial prostate cancer. At the end of genotyping the original set of 400 samples and analyzing the data, we found significant evidence for linkage to a locus on chromosome 1, and suggestive evidence for linkage at 3 additional loci. We shall continue to study prostate cancer, and plan to begin investigating additional familial diseases at the end of the f.y. when our laboratories in building 36 are finally renovated. Drs. Trent and Brownstein have entered into a CRADA with ABD to develop a second-generation marker panel to use for human genotyping. The dreverse primers will all be """"""""pig-tailed"""""""" to guarantee non-templated addition of adenosine to the PCR products and facilitate automated calling of alleles. Drs. Brownstein and Mezey and their coworkers in Colorado (C. Kunst and D.Patterson) have shown that mutant forms of SOD1 have novel interactions with other cellular proteins. These may contribute to the development of ALS. Dr. Brownstein and his coworkers in the NINDS and NHGRI have shown that synuclein is a major component of Lewy bodies and protein deposits in neurites in brains of patients with sporadic Parkinson's disease (PD). Thus, synuclein may be important in the pathogenesis of sporadic as well as familial forms of PD, and perhaps in other illnesses characterized by intracullular protein aggregates as well. Dr. Brownstein participated in a study of the phenotype of enkephalin """"""""knockout"""""""" mice. The animals had exaggerated responses to certain painful stimuli but normal tail flick responses. Studies of pain will be a major focus of the Section. As part of this effort, Dr. Palkovits will characterize pain pathways in mice and look for functional anatomical alterations in knockout animals. After Dr. Hunyady leaves, he will probably not continue to work on transmitters in the gastroinestinal tract even though this has been a very productive area of endeavor and has resulted in several excellent publications. Dr. Clark has published her study of the topology of the GAT-1 transporter, and has completed her investigation of PTH/PTHrp-PTH2 receptor chimers, and has defined receptor domains responsible for ligand selectivity. She and A. Lam will now attempt to clone and define the properties of novel GABA-B receptors.
