Molecular Genetics of Schizophrenia

精神分裂症的分子遗传学

• 批准号: G0800509-E01/1
• 负责人: Michael Owen
• 金额: $ 298.4万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0800509-E01%2F1
• 关键词: Molecular; Genetics; Schizophrenia

Schizophrenia is a severe disorder affecting approximately 1% of the population. Sufferers experience ?psychotic? symptoms, in particular delusions (false beliefs) and hallucinations (false perceptions) usually in the form of hearing voices. They also tend to show disturbed emotions, impairments of thinking and reasoning and bizarre behaviour. Signs can be present from childhood, but usually the disorder is diagnosed in the late teens and early 20?s. This age of onset, combined with the facts that many patients respond poorly or not at all to current treatments, and for those that do respond, relapse is usually frequent, means that the illness typically impacts on the vast majority of an individual?s adult life. This makes schizophrenia a major burden on the patient, their family and wider society. It has been clear for a century that schizophrenia runs in families, and this is now known to be largely due to genes rather than the family environment. Schizophrenia is clearly a brain disease but, despite much research, specific abnormalities that cause the disorder have not been identified. Such knowledge is likely to be required for the development of truly effective treatments. It is our belief that the best hope of identifying the molecular and cellular abnormalities that underlie schizophrenia is to identify specific genes that are involved. This has proven difficult because schizophrenia does not occur as a result of a single genetic mutation, but reflects a large number of different ?risk genes?. It is really the combination of genes inherited at birth, along with as yet unknown environmental factors, that determine someone?s risk. Modern genetic methods are, for the first time, allowing the great majority of variation in a person?s DNA to be identified in a single experiment and will soon allow the whole DNA sequence to be obtained from individuals at realistic costs. Since people with schizophrenia are relatively unlikely to have children, it is likely that one class of genetic risk factor that will be important are new mutations that arise relatively frequently in the population. We have recently obtained evidence that this is the case, and are now proposing to use new technology to find many more of these by obtaining the sequence of all the genes in 700 patients and their parents. Identifying these mutations and studying the function of the genes they affect will help us understand how schizophrenia arises and to identify molecular targets for new treatments.

精神分裂症是一种严重的疾病，影响约1%的人口。患者的经验？精神病？症状，特别是妄想（错误信念）和幻觉（错误感知），通常以听到声音的形式出现。他们还往往表现出情绪不安、思维和推理能力受损以及行为怪异。症状可以从儿童时期就出现，但通常这种疾病是在青少年后期和20岁出头被诊断出来的。S.这种发病年龄，加上许多患者对目前的治疗反应不佳或根本没有反应，而对于那些有反应的患者，复发通常很频繁，这意味着这种疾病通常会影响绝大多数人？的成年生活。这使得精神分裂症成为患者，他们的家庭和更广泛的社会的主要负担。世纪以来，精神分裂症在家族中的遗传已经很清楚，现在人们知道这主要是由于基因而不是家庭环境。精神分裂症显然是一种脑部疾病，但尽管进行了大量研究，导致这种疾病的具体异常尚未确定。这些知识可能是开发真正有效的治疗方法所必需的。我们相信，确定精神分裂症的分子和细胞异常的最大希望是确定涉及的特定基因。这已被证明是困难的，因为精神分裂症的发生不是由于单一的基因突变，而是反映了大量不同的？风险基因？真的是出生时遗传的基因，沿着至今未知的环境因素，决定了一个人吗？的风险。现代遗传学方法第一次允许一个人的绝大多数变异。在一个单一的实验中鉴定的DNA，并将很快允许整个DNA序列，以现实的成本从个人获得。由于精神分裂症患者相对不太可能有孩子，因此有一类重要的遗传风险因素可能是人群中相对频繁出现的新突变。我们最近获得的证据表明情况确实如此，现在我们正计划使用新技术，通过获得700名患者及其父母的所有基因序列来发现更多的此类基因。识别这些突变并研究它们影响的基因功能将有助于我们了解精神分裂症是如何发生的，并确定新治疗的分子靶点。