Mapping the genetic architecture of global gene and exon expression in the human brain to understand common diseases

绘制人脑全局基因和外显子表达的遗传结构，以了解常见疾病

• 批准号: G0901254/1
• 负责人: John Hardy
• 金额: $ 127.48万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901254%2F1
• 关键词: Mapping; genetic; architecture; global; gene

Diseases affecting the brain are common and often devastating. Unfortunately, we know relatively little about why certain people suffer from psychiatric conditions like schizophrenia, or neurological conditions like Alzheimer?s and Parkinson?s disease. However, in the past 3 years scientists have been able to show that some individuals inherit risk factors in their DNA, which make them more likely to develop these conditions. Although this has been an amazing step forward, because most of the inherited risk factors are not within the part of the DNA that codes for proteins we still do not understand how these risk factors change the way cells in the brain behave to cause disease. Without this type of information we cannot begin to develop new and more effective treatments. The aim of our work is to fill this gap in knowledge by investigating how inherited risk factors influence gene expression in the human brain so that we can better understand the causes of neurological and psychiatric disease. We hope to identify genetic variants in the DNA which not only increase the risk of having a disease of the brain, but also affect gene expression in brain regions already known to be important in disease. In this way we can start to pinpoint the systems or pathways in brain cells, which are causing the problem and hopefully provide the basic information that will lead to new treatments.In this study we will use human brain tissue that has been donated for research by the deceased?s family to study the effect of inherited risk factors on the quantity and type of gene expression in different areas of the brain. We will use microarray technology to obtain detailed genetic and gene expression information about human brain tissue. The huge amount of information generated will be carefully analysed. The information this study will produce is likely to be of use to many researchers investigating a wide range of different diseases of the brain. Therefore, we will make sure that the results are made publicly available as soon as possible, while at the same time ensuring that information that could be used to identify individuals is protected.Thus, we hope to be able to improve the understanding of the molecules and pathways that cause diseases of the brain and provide the basis for new treatments for diseases like Parkinson?s or schizophrenia.

影响大脑的疾病很常见，而且往往具有毁灭性。不幸的是，我们对为什么某些人患有精神分裂症等精神疾病或阿尔茨海默病和帕金森病等神经系统疾病知之甚少。然而，在过去的三年里，科学家们已经能够证明，一些人的 DNA 中遗传了危险因素，这使得他们更有可能患上这些疾病。尽管这是一个惊人的进步，但由于大多数遗传性风险因素并不在编码蛋白质的 DNA 部分内，我们仍然不明白这些风险因素如何改变大脑细胞导致疾病的行为方式。如果没有此类信息，我们就无法开始开发新的、更有效的治疗方法。我们工作的目的是通过研究遗传风险因素如何影响人脑基因表达来填补这一知识空白，以便我们更好地了解神经和精神疾病的原因。我们希望识别 DNA 中的遗传变异，这些变异不仅会增加患大脑疾病的风险，还会影响已知在疾病中起重要作用的大脑区域的基因表达。通过这种方式，我们可以开始查明导致问题的脑细胞系统或通路，并有望提供导致新治疗方法的基本信息。在这项研究中，我们将使用死者家属捐赠用于研究的人类脑组织来研究遗传风险因素对大脑不同区域基因表达数量和类型的影响。我们将利用微阵列技术来获得有关人类脑组织的详细遗传和基因表达信息。所产生的大量信息将被仔细分析。这项研究将产生的信息可能对许多研究各种不同大脑疾病的研究人员有用。因此，我们将确保结果尽快公开，同时确保可用于识别个体的信息受到保护。因此，我们希望能够提高对引起大脑疾病的分子和通路的理解，并为帕金森症或精神分裂症等疾病的新治疗方法提供基础。