The Genetic Basis of Hereditary Liver Disease

遗传性肝病的遗传基础

• 批准号: 6325448
• 负责人: LAURA N BULL
• 金额: $ 23.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6325448
• 关键词: RNase protection assay; artificial chromosomes; cholestasis; clinical research; computer assisted sequence analysis; congenital biliary tract disorder; fluorescence microscopy; gene expression; gene mutation; genetic disorder; genetic mapping; genetic markers; genetic screening; genotype; human genetic material tag; immunocytochemistry; in situ hybridization; laboratory mouse; liver disorder; lymphedema; molecular pathology; northern blottings; western blottings

DESCRIPTION (Investigator's abstract): The goals of this project are to identify and characterize the molecular bases for two forms of inherited liver disease, cholestasis-lymphedema syndrome (CLS) and familial hyperbileacidemia (FHB). We will work toward this goal through the following three specific aims: 1) identify the gene mutated in CLS, and further genetically characterize this disorder; 2) characterize the expression pattern of the CLS gene and protein; and 3) identify the gene mutated in FHB, and further genetically characterize this disorder. These genes will be genetically localized through use of recently developed, highly efficient genetic mapping techniques, and then candidate genes identified through analysis of available sequence databases, and use of laboratory-based gene identification techniques. Mutations causing CLS and FHB will be identified, and clinical data examined to identify any correlations between the type of mutation present in a patient, and the characteristics of that patient's disease. The types of cells in which the CLS gene is expressed will be identified using in situ hybridization approaches, and the cellular and subcellular localization of the CLS protein will be characterized, using immunohistochemical techniques. The identification of genes mutated in hereditary disorders, and the subsequent characterization of their protein products, has become a valuable tool for increasing our understanding of the pathophysiology of diseases, including disorders of the hepatobiliary system, which affect millions of people in the U.S. Identification of the genetic cause of a disease assists in diagnosis, and also aids further study that may lead to better treatment and prevention. Most importantly, the identification of a disease gene provides specific insight into the biological pathways that are deranged in the illness, and tools for further study of these pathways.

描述（调查员的摘要）：该项目的目标是 识别和表征两种形式的遗传肝脏的分子碱基 疾病，胆汁淤积 - 淋巴水肿综合征（CLS）和家族性高血压血症 （FHB）。我们将通过以下三个特定目标来朝着这个目标努力： 1）确定CLS中突变的基因，并进一步遗传表征这一点 紊乱; 2）表征CLS基因和蛋白质的表达模式； 3）确定在FHB中突变的基因，并进一步遗传表征 这个疾病。这些基因将通过使用 最近开发了高效的遗传学映射技术，然后 候选基因通过分析可用序列数据库的分析， 并使用基于实验室的基因识别技术。引起的突变 CLS和FHB将被识别，并检查了临床数据以确定任何 患者存在突变类型与 该患者病的特征。 CLS的细胞类型 表达基因将使用原位杂交方法识别 CLS蛋白的细胞和亚细胞定位将是 使用免疫组织化学技术来表征。识别 基因在遗传性疾病中突变，随后的表征 他们的蛋白质产品已成为增加我们的宝贵工具 了解疾病的病理生理学，包括 肝胆系统，影响美国数百万人 鉴定疾病的遗传原因有助于诊断，也有助于 AIDS进一步的研究可能会导致更好的治疗和预防。最多 重要的是，疾病基因的鉴定提供了特定的见解 进入疾病中危险的生物学途径和工具 进一步研究这些途径。