Molecular Genetics of Schizophrenia

精神分裂症是一种严重的疾病，影响大约1%的人口。患者的经历？精神错乱？症状，特别是妄想(错误的信念)和幻觉(错误的感知)，通常以听觉声音的形式出现。他们还倾向于表现出不安的情绪、思维和推理的障碍以及奇怪的行为。这种疾病可以从童年起就有症状，但通常在十几岁后期和20岁出头被诊断出来--S。这个发病年龄，再加上许多患者对目前的治疗反应很差或根本没有反应，而对那些有反应的人来说，复发通常是频繁的，这意味着这种疾病通常会影响绝大多数人的成年生活？S。这使得精神分裂症成为患者、他们的家人和更广泛的社会的主要负担。一个世纪以来，人们已经清楚地知道，精神分裂症是由家族遗传的，现在人们知道这在很大程度上是由基因而不是家庭环境造成的。精神分裂症显然是一种脑部疾病，但尽管有很多研究，导致这种疾病的具体异常还没有被识别出来。这些知识可能是开发真正有效的治疗方法所必需的。我们认为，识别精神分裂症背后的分子和细胞异常的最大希望是识别相关的特定基因。这已经被证明是困难的，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。确实是出生时遗传的基因组合，加上未知的环境因素，决定了一个人？S的风险。现代遗传学方法首次允许在一次实验中识别出一个人的绝大多数变异--S的dna，并将很快以现实的成本从个人身上获得整个dna序列。由于精神分裂症患者相对不太可能生育孩子，很可能有一类重要的遗传风险因素是在人群中相对频繁出现的新突变。我们最近获得了这种情况的证据，现在正在提议使用新技术通过获取700名患者及其父母的所有基因序列来发现更多这样的基因。识别这些突变并研究它们影响的基因的功能将有助于我们了解精神分裂症是如何发生的，并为新的治疗方法确定分子靶点。

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.