GENETIC STUDIES OF HUMAN PIGMENTATION DISORDERS

描述（改编自研究者摘要）：由于其 容易明显的临床表型，色素沉着障碍是其中 人类第一次发现的遗传疾病 其中最严重的 是视觉通路的眼皮肤白化病缺陷， 因此视力低下，易患皮肤癌，以及各种 其它问题. 这里提出的研究计划的目标是扩大 人类OCA基因的长期研究。 第一个具体目标 是继续对已知的OCA基因进行突变和功能分析， 特别是与OCA 2相关的P基因。 第二个具体目标是 完成赫尔曼斯基-普德拉克基因的定位克隆 综合征，一种与致死性溶酶体贮积症相关的OCA形式 和出血素质。 这将允许突变分析，特别是 HPS高危人群，以及人类的特征 和小鼠HPS基因以及HPS基因产物的功能分析。 这些 研究应该为开发特定的药理学打开大门， 也许最终能用基因疗法治疗HPS 第三个具体目标是 定位和克隆一个新的主要的人类OCA基因座，并进行 该基因的最终突变和功能分析及其 多肽。

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.