Susceptibility genes for schizophrenia genome-wide search for copy-number variations (CNVs) in schizophrenic psychoses with phenotype correlation.

精神分裂症被认为是一种复杂的特征，是由遗传和共同的环境病因影响造成的。在寻找精神分裂症遗传风险因素方面的一个重要进展是发现了DNA的结构变异，称为拷贝数变异（CNVs），具有遗传或由假设的高外显率的新生突变引起的特定DNA片段的丢失或获得。我们申请资助一项研究奖学金，在Illumina平台上对200名被归类为ICD 10型精神分裂症的患者进行全基因组CNV筛选，这些患者的表型根据Leonhards分类为摆线性精神病或系统性精神分裂症。所有200名受试者的父母的DNA都是可用的，这将使我们能够检查任何有希望的新生CNV。实验室工作和统计分析将在英国加的夫威尔士大学医学研究委员会神经精神遗传学和基因组学中心进行。摆线型精神病和系统性精神分裂症的阳性家族史发生率极低。家族史阳性率低，使系统性精神分裂症和摆线型精神病组非常适合检测新生CNVs，因为前代没有疾病传播。在表现型方面，摆线型精神病和系统性精神分裂症表现为不同的极端，病程有阶段性或慢性进行性。到目前为止，已确定的致病性CNVs与特定表型无关，也增加了自闭症和智力迟钝的风险。对影响基因、相关通路、症状维度和临床表型的相关性分析，可能为精神分裂症生物学基础中的基因网络、细胞和调控通路提供新的认识。

The group of schizophrenic psychoses are thought to be complex traits that result from both genetic and shared environmental aetiological influences. An important progress in search for genetic risk factors in schizophrenia has been the discovery of structural variations of DNA, called copy number variants (CNVs), with loss or gain of specific DNA segments either inherited or caused by de novo mutation with assumed high penetrance. We apply for funding a research fellowship to perform a genome-wide CNV screen on an Illumina platform in 200 individuals who are classified as suffering from ICD 10 schizophrenia and who are phenotyped according to Leonhards classification as cycloid psychoses or systematic schizophrenias. DNA from the parents of all 200 subjects is available and will allow us to examine any promising CNV for de novo occurrence. The laboratory work and statistical analysis will be performed at the Medical Research Council¿s Centre for Neuropsychiatric Genetics and Genomics at the University of Wales, Cardiff, UK. Patients with cycloid pychoses and systematic schizophrenias have extremely low rates of positive family history. The low rate of positive family history makes the groups of systematic schizophrenias and cycloid psychoses very suitable for detection of de novo CNVs, as there is no transmission of illness in previous generations. Regarding phenotype cycloid psychoses and systematic schizophrenias represent different extremes with phasic or chronic progressive course of disease. The pathogenic CNVs that have been identified so far have not been associated with specific phenotypes, increasing risk also for autism and mental retardation. Correlation analysis of the affected genes, related pathways, symptom dimensions and clinical phenotypes might give new insight in gene networks, cellular and regulatory pathways in the biological foundation of the schizophrenic psychoses.