Genetic Analysis of Parkinsonism in an Ohio Amish Family

俄亥俄州阿米什家庭帕金森病的遗传分析

• 批准号: 7116765
• 负责人: Stephen L. Lee
• 金额: $ 16.57万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116765
• 关键词: Mennonite; Parkinson' s disease; clinical research; environmental exposure; family genetics; gene mutation; genetic screening; human genetic material tag; human middle age (35-64); human old age (65+); human subject; linkage mapping; medical records; patient oriented research; phenotype; ubiquitin

DESCRIPTION (provided by applicant): Disease genes discovered through linkage analysis in familial Parkinson disease (PD) are yielding new insights into the pathogenesis of this neurodegenerative disorder. However, the known genes explain only a minor portion of all PD, and the chromosomal regions linked to other families are large and contain numerous genes. The discovery of additional hereditary causes of PD may help further elucidate the underlying etiopathogenesis and provide new pharmacological targets. It is therefore crucial that additional families are characterized. In an extended Amish family in northeastern Ohio, clinical information for familial Parkinsonism has been obtained. To test the hypothesis that genetic influences contribute to the expression of Parkinsonism in this Amish pedigree, the immediate aims of this project are three-fold: 1) to fully ascertain the disease phenotype of the affected individuals, through genealogical data, clinical history, medical records, and neurological exam, 2) to identify the genetic locus or loci associated with the disease phenotype, initially by evaluating previously identified genetic loci, and conducting a genome-wide scan using conventional linkage analysis, transcript mapping, and gene identification, and 3) to perform candidate gone analysis to test whether specific gene modifiers enhance or suppress the expression of the disease phenotype. The candidate's long-term goals are to apply well-established and emerging methods toward understanding the genetic basis of Parkinsonism. This grant will help the candidate establish an independent career in academic neurology with specialization in movement disorders and neurogenetics by allowing the candidate 1) to evaluate and treat patients in a movement disorders clinic under the guidance of Thomas L. Davis, M.D., and 2) to learn the laboratory, statistical, and computational methods of genetic epidemiology. This will be accomplished through conduct of the proposed research project and participation in formal courses under the guidance of the candidate's mentor, Jonathan L. Haines, Ph.D.

描述（由申请人提供）：通过家族性帕金森氏病（PD）发现的疾病基因正在对这种神经退行性疾病的发病机理产生新的见解。但是，已知的基因仅解释了所有PD的一小部分，与其他家族相关的染色体区域很大，并且包含许多基因。发现其他PD的遗传原因可能有助于进一步阐明潜在的疗法生成并提供新的药理靶标。因此，至关重要的是要表征更多的家庭。在俄亥俄州东北部的一个扩展的阿米什（Amish）家庭中，已经获得了家族性帕金森氏症的临床信息。为了检验遗传影响的假说在这种阿米什人的血统中有助于帕金森氏症的表达，该项目的直接目的是三个方面：1）完全确定受影响个体的疾病表型，通过谱系数据，临床病史，医疗记录和神经学检查与遗传学或位置相关的遗传型，2）使用常规连锁分析，转录本映射和基因鉴定以及3）进行候选分析以测试特定基因修饰剂是否增强或抑制疾病表型的表达来进行候选分析，以进行全基因组扫描。候选人的长期目标是将良好的新兴方法应用于理解帕金森主义的遗传基础。这项赠款将通过允许候选人允许候选人和神经遗传学的专业化来帮助候选人在学术神经病学领域建立独立的职业。这将通过拟议的研究项目的进行和参加正式课程的指导来实现，并在候选人的导师Jonathan L. Haines博士的指导下完成。