The Genetic Basis of Hereditary Liver Disease

遗传性肝病的遗传基础

• 批准号: 6524295
• 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/6524295
• 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（研究者的摘要）：该项目的目标是 识别和表征两种形式遗传性肝脏的分子基础 疾病、胆汁淤积-淋巴水肿综合征 (CLS) 和家族性高胆汁酸血症 （食物及卫生局）。我们将通过以下三个具体目标来实现这一目标： 1）识别CLS中突变的基因，并进一步对其进行遗传学表征 紊乱; 2)表征CLS基因和蛋白的表达模式； 3) 鉴定FHB中突变的基因，并进一步进行遗传表征 这种紊乱。这些基因将通过使用进行遗传定位 最近开发的高效遗传图谱技术，然后 通过分析可用序列数据库确定的候选基因， 以及基于实验室的基因鉴定技术的使用。突变导致 将识别 CLS 和 FHB，并检查临床数据以识别任何 患者体内存在的突变类型与 该患者的疾病特征。 CLS 所在的细胞类型 将使用原位杂交方法鉴定表达的基因， CLS 蛋白的细胞和亚细胞定位将是 使用免疫组织化学技术进行表征。鉴定 遗传性疾病中的基因突变，以及随后的特征 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，包括疾病 肝胆系统，影响着美国数百万人 确定疾病的遗传原因有助于诊断，而且 有助于进一步研究，从而更好地治疗和预防。最多 重要的是，疾病基因的识别提供了具体的见解 深入了解疾病中紊乱的生物途径，以及治疗疾病的工具 进一步研究这些途径。