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。

• 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
• 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

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.

项目总结/摘要 据估计，帕金森病（PD）影响全球超过700万人。没有治愈的方法， 治疗只能减轻症状而不能阻止神经元的损失。由于电机的阵列和严重性， 和非运动症状，这对他们的生活质量也有显着影响 和他们的看护者一样迫切需要进一步研究使某些人 患帕金森病的风险更高研究表明，PD具有显著的遗传成分， 已经发现了许多基因，但是这些研究主要是在高加索人和 亚洲人口。到目前为止，只有不到10篇关于黑人PD的遗传学研究发表。 人口。这些患者在新的PD致病基因中携带致病性突变是合理的。的 parkin和PINK 1等基因的发现，揭示了帕金森病潜在的疾病机制 包括线粒体功能障碍，线粒体自噬和氧化应激，因此确定其他新的PD 基因的研究有可能揭示这种疾病的病理生物学的重要见解。因此 我们必须对黑人PD患者进行更多的研究。在拟议的研究中，我们将审查 假设黑人PD患者由于其独特的祖先而在新的PD致病基因中携带突变。 这个R21项目旨在建立尼日利亚、南非和 美国研究这三个国家黑人患者PD的遗传原因。我们的目标是招募一名 在尼日利亚和南非至少有100名黑人PD患者进行遗传学研究，筛查致病性 已知的PD致病基因以及一组751个神经相关基因的突变。 此外，我们将建立一个试点研究，以筛选线粒体DNA的突变。最后，我们将比较 并将这三个人群的临床和遗传发现与其他已发表的 问题研究在该项目的两年时间里，将通过以下方式发展尼日利亚的帕金森病研究能力： 为患者招募、随访和临床评估建立基础设施。南非的能力将是 通过集中招募黑人PD患者，并建立高通量 有针对性的重新测序方法。美国的能力将通过获得大量 黑人患者数量和线粒体DNA测序方法的建立。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- R 01级补助金申请。这项研究的总体影响是，通过鉴定新的PD基因， 了解神经退行性变的疾病机制，最终这将为更多的设计提供信息。 不仅对PD而且对其他形式的神经退行性疾病都是有效的治疗方法。