Identification and characterization of the DFNB17 gene

DFNB17 基因的鉴定和表征

• 批准号: 6743956
• 负责人: JOHN H GREINWALD
• 金额: $ 19.15万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-15 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6743956
• 关键词: autosomal recessive trait; chromosome disorders; clinical research; complementary DNA; disease /disorder etiology; disease /disorder proneness /risk; family genetics; functional /structural genomics; gene expression; gene mutation; genetic disorder; genetic mapping; genetic markers; genetic regulatory element; genetic susceptibility; hearing disorders; human genetic material tag; human subject; laboratory mouse; molecular cloning; patient oriented research; polymerase chain reaction

DESCRIPTION (provided by applicant): The primary goal of this proposed research project is to determine the disease-causing mutation of the gene responsible for the seventeenth loci for autosomal recessive non-syndromic hearing loss (DFNB17), and to characterize its expression and function in the inner ear. Hereditary hearing impairment (HHI) affects approximately 1 in 1000 children and constitutes one of the most common birth defects. Because of the long-term problems with language acquisition, development and education, a further understanding of the pathophysiology of hearing impairment is warranted. Based on preliminary linkage data localizing the gene responsible for DFNB17 to a 3cM region of chromosome 7q31, we hypothesize that the deafness-causing mutation is contained within this interval. We will use a positional cloning strategy to test this hypothesis, identify the mutation responsible for DFNB17 and determine its putative functional and expression c characteristics. This project proposes to: 1) Refine and narrow the DFNB17 interval on chromosome 7q31. 2) Identify candidate cochlear expressed genes in the DFNB17 interval. 3) Identify the DFNB17 gene by determining the disease causing mutation in a family mapping the original locus and in novel families mapping to this interval. 4) Determine the expression pattern and putative function of this novel cochlear expressed gene. Secondarily, this project will serve as an opportunity for the principal investigator to acquire the skills and knowledge base to become an independent clinician-scientist. The immediate goals of the candidate are to establish an active research laboratory and study the DFNB17 gene. The long-term career goal is to be an independent clinician-scientist, focused on the study of the molecular genetics of hereditary deafness. Specifically, to identify novel hearing loss related genes, advance the science of molecular diagnostic testing for patients and provide insight into pathways for potential treatments in hearing impaired patients. All of this knowledge can then be directly applied to an otologically based clinical practice at a large pediatric tertiary care referral center to provide the highest quality of care for hearing impaired patients and families. The overall development plan to reach these goals will include a combination of dedicated laboratory time, integrating with and receiving direct support from the Division of Human Genetics with an educational plan which will consist of close association with mentor scientists, dedicated reading course, didactic inter- and extra-divisional interactive sessions and classes and prescribed lectures.

描述（由申请人提供）：这项拟议研究的主要目标 项目是确定导致疾病的基因突变 常染色体隐性非综合听力损失的第十七个基因座 （DFNB17），并表征其在内耳中的表达和功能。 遗传性听力障碍（HHI）影响了大约1000名儿童中的1个 构成最常见的先天缺陷之一。由于长期 语言获取，发展和教育的问题，进一步 有必要了解听力障碍的病理生理学。基于 关于将DFNB17的基因定位到3厘米的初步链接数据 7q31染色体区域，我们假设引起聋哑的突变为 包含在此间隔内。我们将使用位置克隆策略来 检验该假设，确定负责DFNB17的突变并确定 其推定的功能和表达C特征。该项目提出了建议 至：1）在7q31染色体上改进并缩小DFNB17间隔。 2）识别 候选人耳蜗在DFNB17间隔中表达基因。 3）确定 DFNB17基因通过确定疾病引起的疾病，在映射家庭中突变 原始基因座和新的家族映射到此间隔。 4）确定 这种新型人工耳蜗表达基因的表达模式和推定功能。 其次，该项目将成为校长的机会 研究人员获得技能和知识基础，成为独立的 临床医生科学家。候选人的直接目标是建立一个 主动研究实验室并研究DFNB17基因。长期职业目标 是一名独立的临床医生，专注于研究 遗传性耳聋的分子遗传学。具体来说，要识别新颖 与听力损失相关的基因，推进分子诊断测试的科学 适用于患者，并深入了解潜在治疗的途径 听力障碍患者。所有这些知识然后可以直接应用于 大型小儿三级护理中基于耳科学的临床实践 推荐中心为听力障碍提供最高质量的护理 患者和家庭。实现这些目标的整体发展计划将 包括专门的实验室时间的结合，与和 通过教育获得人类遗传学的直接支持 计划包括与导师科学家密切相关，专门的 阅读课程，教学互动和范围的互动会议和 课程和规定的讲座。