Capacity building in sub-Saharan Africa to conduct cutting-edge genetics research in Parkinson's disease.

撒哈拉以南非洲地区开展帕金森病前沿遗传学研究的能力建设。

基本信息

批准号：
9199863
负责人：
Soraya Bardien
金额：
$ 13.43万
依托单位：
STELLENBOSCH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9199863
关键词：
Accounting Affect Africa South of the Sahara African African American Applications Grants Arabs Ashkenazim Asians Biological Blood specimen Brain Caregivers Caucasians Characteristics Clinic Clinical Clinical Research Clinical assessments Collaborations Complex Copy Number Polymorphism Country DNA DNA Sequence Data Demographic Transitions Development Dideoxy Chain Termination DNA Sequencing Disease Drug Design Educational workshop Epidemic Foundations Founder Effect Frequencies Funding Opportunities Future Genes Genetic Genetic Predisposition to Disease Genetic Research Genetic study Goals Individual Knowledge LRRK2 gene Laboratories Life Ligation Light Longevity Medical Genetics Mission Mitochondrial DNA Monitor Mutation National Institute of Neurological Disorders and Stroke National Institute on Aging Nerve Degeneration Neurologic Nigeria Nigerian Oxidative Stress PINK1 gene Parkinson Disease Participant Pathway interactions Patient Recruitments Patients Pilot Projects Population Prevalence Public Health Publishing Quality of life Recruitment Activity Reporting Research Research Infrastructure Research Personnel Research Project Grants Risk Factors Saliva Sample Size Sampling Severities Site Solid South Africa South African Targeted Resequencing Teaching Hospitals Techniques United States National Institutes of Health Universities Variant Visit World Health Organization age related base burden of illness cost effective design disability-adjusted life years disease-causing mutation disorder risk effective therapy experience follow-up follower of religion Jewish gene discovery genetic risk factor high risk insight international center meetings member mitochondrial dysfunction motor symptom mutation screening nervous system disorder neuron loss non-motor symptom novel parkin gene/protein programs reduce symptoms response

项目摘要

PROJECT SUMMARY/ ABSTRACT Parkinson’s disease (PD) is estimated to affect over 7 million people worldwide. There is no cure and current treatment only alleviates the symptoms and do not stop neuronal loss. Due to the array and severity of motor and non-motor symptoms experienced by PD patients this has a significant effect on their quality of life as well as that of their caregivers. Further studies are urgently needed on the risk factors that place certain individuals at higher risk for PD development. It has been shown that PD has a significant genetic component and a number of genes have been discovered however these studies were predominantly done on Caucasian and Asian populations. To date, there have been fewer than 10 published genetic studies on PD in Black populations. It is plausible that these patients harbor pathogenic mutations in novel PD-causing genes. The discovery of genes such as parkin and PINK1 have shed light on possible disease mechanisms underlying PD including mitochondrial dysfunction, mitophagy and oxidative stress, and hence identification of other novel PD genes has the potential to reveal important insight into the pathobiology of the disorder. It is therefore imperative that more studies are done on Black PD patients. In the proposed study we shall examine the hypothesis that Black PD patients harbor mutations in novel PD-causing genes due to their unique ancestry. This R21 project aims to build collaborative research projects between researchers in Nigeria, South Africa and the USA to study the genetic causes of PD of Black patients from these three countries. We aim to recruit a minimum of 100 Black PD patients in Nigeria and South Africa for genetic studies, screen for pathogenic mutations in the known PD-causing genes as well as a panel of 751 neurologically-associated genes. Moreover, we will set up a pilot study to screen for mutations in mitochondrial DNA. Finally, we will compare and contrast the clinical and genetic findings across the three populations and to that of other published studies. Over the two years of the project, research capacity on PD in Nigeria will be developed through setting up the infrastructure for patient recruitment, follow-up and clinical assessments. Capacity in South Africa will be developed through the focussed recruitment of Black PD patients, and the setting up of high-throughput targeted re-sequencing approaches. Capacity in the USA will be developed through access to large numbers of Black patient numbers and the setting up of the mitochondrial DNA sequencing approach. It is anticipated that the preliminary data produced through this research collaboration will form the basis for a future larger- scale R01 grant application. The overall impact of this study is that by identifying novel PD genes this will shed light on disease mechanisms underlying neurodegeneration and ultimately this will inform the design of more effective therapies for not only PD but also other forms of neurodegeneration.

项目摘要/摘要据估计，帕金森氏病（PD）将影响全球超过700万人。没有治愈和最新治疗只会减轻症状，不会停止神经元丧失。由于电动机的数组和严重程度 PD患者经历的非运动症状也会对其生活质量产生重大影响就像他们的照顾者一样。迫切需要对将某些人放置的风险因素进行进一步的研究 PD开发的风险更高。已经表明，PD具有重要的遗传成分和A 已经发现了基因数量，但是这些研究主要是在高加索人和高加索人和亚洲人口。迄今为止，关于黑色的PD的遗传研究少于10个人群。这些患者在新型PD引起的基因中具有致病性突变是合理的。这发现Parkin和Pink1之类的基因已经揭示了PD潜在的疾病机制包括线粒体功能障碍，线粒体和氧化应激，因此鉴定了其他新型PD 基因有可能揭示对该疾病病原体学的重要见解。因此是必须对黑色PD患者进行更多研究。在拟议的研究中，我们将检查假设黑人PD患者由于其独特的祖先而在新型PD引起基因中具有突变。这个R21项目旨在在尼日利亚，南非和美国研究这三个国家的黑人患者PD的遗传原因。我们的目标是招募尼日利亚和南非至少100名黑人PD患者进行遗传研究，致病性筛查已知引起PD的基因以及751个神经相关基因的突变。此外，我们将建立一项试验研究，以筛选线粒体DNA中的突变。最后，我们将比较并将三个人群的临床和遗传发现与其他已发表的人群进行对比研究。在该项目的两年中，将通过设置开发尼日利亚PD的研究能力提高患者招募，随访和临床评估的基础设施。南非的能力将是通过重点招募黑色PD患者和高通量的建立来开发有针对性的重新测序方法。美国的能力将通过访问大量来开发黑色患者数量和线粒体DNA测序方法的设置。预计通过这项研究合作产生的初步数据将成为未来更大的基础比例R01赠款应用程序。这项研究的总体影响是，通过识别新型PD基因，这将脱落关于神经退行性基础的疾病机制的光明，最终将为您的设计提供更多信息不仅对PD，而且对其他形式的神经变性的有效疗法。