MOLECULAR GENETICS OF USHER SYNDROME III, IIB, AND IA

Usher 综合征 III、IIB 和 IA 的分子遗传学

• 批准号: 6317792
• 负责人: Janos Sumegi
• 金额: $ 16.33万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-12-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6317792
• 关键词: chromosome aberrations; clinical research; congenital deafness; denaturing gradient gel electrophoresis; diagnosis design /evaluation; disease /disorder classification; gene expression; gene mutation; genetic disorder diagnosis; genetic mapping; genetic polymorphism; human genetic material tag; human subject; immunocytochemistry; in situ hybridization; molecular cloning; molecular pathology; nucleic acid sequence; polymerase chain reaction; regulatory gene; retinitis pigmentosa; sequence tagged sites; single strand conformation polymorphism; southern blotting; vestibular apparatus

Usher syndrome is a hereditary disorder that causes congenital hearing loss and retinitis pigmentosa. The three major clinical types, Usher syndrome type (USH1), type II (USH2) and type III of vestibular dysfunction. At least ten distinct genetic loci are now identified as being associated with the three clinical types of the disease. Of the ten Usher loci, two genes, USH1B and USH2A, have been identified. The USH1B encodes MYO7A, an unconventional myosin and USH2A encodes a putative extracellular matrix protein. What, if any, relation is there between these different classes of molecules and they relate to the other Usher genes' products. To address this question, we wish to identify additional Usher genes. We have the family resources to initiate such project. In the present proposal we wish to identify the Usher syndrome type 1A, type 2B and type 3 genes and their products. We will apply standard positional cloning strategy based on the construction of Sequence Tagged Site (STS) maps, integrated YAC/BAC/PAC contig maps and transcript maps for the respective critical regions. The Usher type 1A, 2B and 3 genes will be identified as genes carrying disease causing mutations in their coding or regulatory regions in the affected individuals. The identification of the various Usher genes not only provides an insight into a group of genes whose products play an important role in normal hearing, vision and vestibular function but establishes the possibility of gene based genetic diagnosis of the disease. It will provide insights into the development and the temporal and spatial organization of the inner ear and retina where the defect is believed to originate and will allow us to design therapies.

Usher综合征是一种遗传性疾病，会导致先天性听力损失和色素性视网膜炎。前庭功能障碍的三种主要临床类型，USHER综合征类型（USH1），II型（USH2）和III型。现在，至少十个不同的遗传基因座被确定为与该疾病的三种临床类型有关。在十个USHER基因座中，有两个基因，USH1B和USH2A。 USH1b编码MyO7a，一种非常规肌球蛋白，USH2A编码了推定的细胞外基质蛋白。这些不同类别的分子之间存在关系，它们与其他usher基因的产品有关。为了解决这个问题，我们希望确定其他usher基因。我们有家庭资源来启动该项目。在本提案中，我们希望确定1A型Usher综合征，2B型和3型基因及其产品。我们将根据序列标记位点（STS）映射的构建，YAC/BAC/PAC重叠群图和转录本图的构建标准位置克隆策略以及相应关键区域的转录图。 1A型，2b和3型基因将被鉴定为携带疾病的基因，该基因在受影响个体的编码或调节区域中引起突变。鉴定各种usher基因不仅可以洞悉一组基因，这些基因在正常的听力，视力和前庭功能中起着重要作用，而且确定了基于基因的遗传诊断的可能性。它将提供有关内耳和视网膜的发展和时间和空间组织的见解，在该内部和视网膜中，缺陷被认为是起源的，并使我们能够设计疗法。