Dr. Brownstein and his coworkers in the NCHGR (Drs. Smith, Carpten, Trent, and Collins) have continued to study the genetic basis of familial prostate cancer. We have genotyped more than 50% of our original set of 400 samples. After we finish genotyping these samples and analyzing the data, we hope to confirm the results of the initial screen by analyzing additional samples we have in hand from the US and Sweden. In addition, we look forward to obtaining samples from Finland in the near future. In parallel with the genotyping, we have developed panels of markers and methods for using them to greater advantage. We discovered a method to eliminate the problem of non-templated addition of nucleotide seen with Taq polymerase, and can now reliably use markers that have alleles differing size from one another by 1 base pair. We shall make a second generation panel of genotyping markers in the next year and plan to begin constructing a panel of mouse markers to exploit differences among mouse strains in complex traits. With the equipment currently available, we can realistically take on projects that involve the genotyping 2000 or more samples. We intend to continue to work in the field of tumor genetics and hope to investigate the genetic underpinnings of schizophrenia as well. Dr. Clark has nearly completed her work on two related projects: studies of the role of N-linked glycosylation in cell surface expression of functional GAT-1 GABA transporters and examination of the transmembrane topology of GAT-1. In addition, she has begun to use PTH/PTHrp-PTH2 receptor chimers to determine the receptor domains responsible for ligand selectivity. Dr. Button has continued to use aequorin to study alterations in free calcium levels induced by drugs and chemical messengers in specific intracellular organelles. He has discovered the strengths and limitations of targeted aequorin constructs. When he leaves in September, we shall no longer pursue this work.
