GENETIC STUDIES OF HUMAN PIGMENTATION DISORDERS

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DESCRIPTION (Adapted from the Investigator's Abstract): Because of their readily apparent clinical phenotypes, disorders of pigmentation were among the first genetic diseases recognized in humans. The most severe of these are the oculocutaneous albinism defects of the visual pathways and consequent low visual acuity, susceptibility to skin cancer, and various other problems. The goal of the research program proposed here is to extend the longstanding investigations of human OCA genes. The first specific aim is to continue mutational and functional analyses of known OCA genes, particularly the P gene, associated with OCA2. The second specific aim is to complete the positional cloning of the gene for Hermansky-Pudlak syndrome, a form of OCA associated with a lethal lysosomal storage disorder and bleeding diathesis. This will permit mutational analyses, especially of populations at high risk for HPS, as well as characterization of the human and mouse HPS genes and functional analyses of the HPS gene product. These studies should open the door to the development of specific pharmacologic and perhaps eventual gene therapies to HPS. The third specific aim is to map and positionally clone a novel major human OCA locus, and to carry out eventual mutational and functional analyses of this gene and its polypeptide.