My colleagues in the National Human Genome Research Institute and I have continued to study a number of complex and Mendelian genetic traits in humans. We reported a second locus on the X chromosome linked to familial prostate cancer, and made good progress in our search for a prostate cancer gene on chromosome 1. In addition, we nearly completed a genome-wide search for linkage in samples from Australian families with > 3 cases of melanoma, and began to genotype families on Kosrae with schizophrenia. We found evidence for linkage in two traits--autosomal dominant (AD) Duane's syndrome, and autosomal recessive sitosterolemia, and are looking for mutations in candidate genes in the former. Finally, we found specific genetic alterations in two human disorders--AD progressive punctate cataracts and AD Parkinsonism. In the latter there was a missense mutation in the gamma D-crystallin gene; in the former, a missense mutation in the ubiquitin hydrolase gene. Based on our work to date, we have argued that Parkinsonism results from excessive aggregation of mutant or damaged protein or reduced metabolism of protein in nigral neurons.
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