GENETICS OF PARKINSON DISEASE IN THE AMISH

阿米什人帕金森病的遗传学

基本信息

批准号：
7100949
负责人：
Brad A Racette
金额：
$ 16.22万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-15 至 2008-04-30
项目状态：
已结题

项目摘要

The applicant is a neurologist and movement disorders specialist with three years of post-fellowship, faculty experience involving clinical care, clinical trials, and clinical research into etiologic risk factors for PD including genetic factors. The goal of this career development award is to provide the applicant with comprehensive training in genetic epidemiology through course work, individual tutorials, and practical application of gene mapping techniques to a multi-incident Amish family with Parkinson Disease (PD). PD is a neurodegenerative disorder that produces substantial disability for nearly 1 million people in North America. There is no known cause of the disease in the majority of patients; however, a genetic etiology has been found in a few rare multi-incidence families. Identification of such genes and subsequent determination of the cell biological effects of these mutations will provide important clues to the pathophysiology. Each new mutation discovered adds critical converging evidence about pathophysiological mechanisms common to all to those affected with PD. We have identified 27 members of a large Amish family with clinically typical PD and have excluded known PD genetic mutations. However, we still need to prove that PD is inherited in this pedigree. We will use two different methods to prove that PD in this kindred has a genetic basis. The first approach will assume an autosomal recessive model of inheritance and use genetic marker data provided by CIDR on our subjects to perform homozygosity mapping. A second approach will be to calculate a kinship coefficient to determine if the affected members of the pedigree are "more related" than randomly selected age-matched individuals from the same population. Finally, we will test whether [18]FDOPA PET permits the conversion of some people identified clinically as possible or probable PD in to PET-confirmed PD and thereby functioning as an endophenotype for disease state. This family provides a unique opportunity for the candidate to become a productive independent investigator in genetics of Parkinson Disease and other movements disorders and to develop skills needed for interpretation of [18]FDOPA PET.

申请人是一名神经科医生和运动障碍专家，具有三年的临时职业，涉及临床护理，临床试验的教师经验以及对PD（包括遗传因素）的病因学风险因素的临床研究。该职业发展奖的目的是通过课程工作，个别教程以及将基因映射技术的实际应用在帕克森氏病（PD）的多个敌对的阿米什人家庭中，为申请人提供遗传流行病学的全面培训。 PD是一种神经退行性疾病，可为北美近100万人产生实质性残疾。大多数患者没有已知的原因。然而，在一些罕见的多重生命科中发现了遗传病因。这些基因的鉴定以及随后确定这些突变的细胞生物学作用将为病理生理提供重要的线索。发现的每个新突变都为所有受PD影响的人所共有的病理生理机制增加了关键的融合证据。我们已经确定了一个临床上典型PD的大型阿米什人家族的27名成员，并排除了已知的PD基因突变。但是，我们仍然需要证明PD是在此血统中遗传的。我们将使用两种不同的方法来证明此类pd具有遗传基础。第一种方法将采用遗传的常染色体隐性模型，并使用CIDR对我们受试者提供的遗传标记数据进行纯合性映射。第二种方法是计算亲属系数，以确定血统的受影响成员是否比来自同一人群的随机年龄匹配的个体“相关”。最后，我们将测试[18] FDOPA PET是否允许某些人在临床上或可能的PD识别为PET确认的PD，从而作为疾病状态的内型型。这个家庭为候选人提供了一个独特的机会，成为帕金森氏病和其他运动疾病遗传学生产性的独立研究者，并发展[18] FDOPA PET所需的技能。