Clinical and genetic studies of hereditary neurological disorders in Mali

马里遗传性神经系统疾病的临床和遗传学研究

• 批准号: 10208922
• 负责人: GUIDA LANDOURE
• 金额: $ 24.99万
• 依托单位: UNIV OF SCIENCES, TECH & TECH OF BAMAKO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-27 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10208922
• 关键词: Affect; Africa; Africa South of the Sahara; African; Award; Awareness; Biology; Birth; Cell Culture Techniques; Cessation of life; Clinical; Clinical Research; Communicable Diseases; Communities; Country; Defect; Developed Countries; Disease; Ensure; Environment; Family; Family history of; Fertility Rates; Funding; Future Generations; Gene Mutation; General Population; Genes; Genetic; Genetic Counseling; Genetic Diseases; Genetic Services; Genetic study; Genomics; Goals; Government; Health; Health Care Costs; Human Inbreeding; Individual; Infrastructure; Inherited; Knowledge; Lead; Lifting; Local Government; Mali; Medical Genetics; Modeling; Molecular; Molecular Biology; Mutation; Neurodegenerative Disorders; Neurologic; Patients; Phenotype; Physicians; Politics; Population; Population Genetics; Prevalence; Productivity; Public Health; Reporting; Research; Research Training; Resources; Scientist; Ships; Specialist; Students; Therapeutic; Training; Ursidae Family; Variant; Vulnerable Populations; Woman; Work; base; care seeking; community engagement; disability; disability-adjusted life years; disease-causing mutation; exome sequencing; genetic testing; genetic variant; interest; literacy; neglect; nervous system disorder; next generation; novel; premature; prevent; productivity loss; psychosocial; rare genetic disorder; social factors; social stigma

Summary Despite the vast diversity of its populations, genetic studies in Africa have been limited. African populations, Malians in particular, have a high rate of intra-ethnic and consanguineous marriage, resulting in increased prevalence of autosomal recessive diseases. Family-based genetic studies can be limited in developed countries due to small sib ships. The average fertility rate in Mali is over 6 births per woman, offering a unique opportunity to find new disease genes or mutations that can then be studied in other populations. Neurological disorders present public health challenges globally with total disability- adjusted life years (DALYs) greater than some infectious diseases. These challenges are even greater when considering hereditary neurological diseases that cause premature death, severe disability and loss of productivity, resulting in high health care costs. Although most are currently untreatable, increasing awareness and community engagement about hereditary neurological disorders can reduce this burden. Our previous studies have established the molecular defects in a good number of families and identified variants in novel genes. Through genetic counseling and community engagement session, patients and families as well as their communities have gained knowledge regarding the cause of these diseases; lifting in part the psychosocial burden, and orienting their partner choice. However, more work is needed for a full understanding of the mechanism of these diseases. Despite the increased number of trained physicians and students in the characterization of these diseases and the basics in genetics, many other families haven’t gotten access to medical genetic services. Standard genetic testing in several other families has been inconclusive, confirming our premise that Malians have specific phenotypic variants of hereditary neurological disorders that may be due to novel mutations or to mutations in as yet undiscovered genes. The infrastructures built with the previous award have created a suitable environment to perform state-of-art research and train the next generation African scientists. To ensure sustainability, African government should be fully engaged to empower genetic training and research funding. With this support, African scientists and clinicians would be ready to meet emerging medical genetics and genomic challenges. With the commitment of some African leaders and philanthropists, there is a hope that Africans will soon fund a big part of the research in Africa.

摘要 尽管非洲人口的多样性很大，但非洲的基因研究一直是 有限的。非洲人口，特别是马里人，有很高的种族内和 近亲婚姻，导致常染色体隐性遗传患病率增加 疾病。基于家庭的基因研究在发达国家可能受到限制，因为 小型兄弟船。马里的平均生育率超过每名妇女6个孩子，提供了 发现新的疾病基因或突变的独特机会 在其他种群中进行了研究。 神经性疾病给全球公共卫生带来了完全残疾的挑战- 调整寿命年(DALY)大于某些传染病。这些 当考虑到遗传性神经疾病时，挑战甚至更大 导致过早死亡、严重残疾和生产力丧失，导致 医疗保健费用。尽管大多数目前无法治愈，但人们越来越意识到 而社区对遗传性神经疾病的参与可以减少这一点 负担。 我们之前的研究已经确定了大量的分子缺陷 新基因中的家族和已识别的变异。通过遗传咨询和 社区参与会议、患者和家属以及他们的社区 获得了关于这些疾病的原因的知识；解除了部分 心理社会负担，以及指导他们的伴侣选择。然而，更多的工作是 需要对这些疾病的机制有充分的了解。尽管 更多训练有素的医生和学生了解这些疾病的特征 疾病和遗传学的基本知识，许多其他家庭没有机会获得 医学基因服务。在其他几个家庭中进行的标准基因检测已经 不确定，证实了我们的假设，即马里人有特定的表型变异 遗传性神经疾病，可能是由于新的突变或 尚未发现的基因突变。 上一次获奖建造的基础设施创造了一个合适的 进行最先进的研究和培训下一代非洲人的环境 科学家们。为了确保可持续性，非洲政府应该充分参与 为遗传培训和研究提供资金。在这种支持下，非洲科学家 临床医生将准备好迎接新兴的医学遗传学和基因组学 挑战。在一些非洲领导人和慈善家的承诺下， 是希望非洲人很快就能为非洲的大部分研究提供资金。