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

这组精神分裂症精神病患者被认为是遗传和共同环境病因学影响的复杂特征。在寻找精神分裂症遗传危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(CNV)，特定DNA片段的丢失或获得可能是遗传的或由假设的高外显性的从头突变引起的。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精神分裂症的人进行全基因组CNV筛查，并根据Leonhard分类将他们分型为摆动式精神病或系统性精神分裂症。所有200名受试者父母的DNA都是可用的，这将使我们能够检查任何有希望的CNV从头开始发生。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S神经精神病学遗传学和基因组学中心进行。患有摆状精神分裂症和系统性精神分裂症的患者有极低的阳性家族史。家族史阳性率低，这使得系统性精神分裂症和摆线精神病非常适合检测新生CNV，因为在前几代中没有疾病的传播。就表型而言，摆线精神病和系统性精神分裂症表现为阶段性或慢性进行性病程的不同极端。到目前为止，已发现的致病CNV还没有与特定的表型相关，这也增加了患自闭症和智力低下的风险。对受累基因、相关通路、症状维度和临床表型的相关性分析，可能会对精神分裂症的生物学基础中的基因网络、细胞和调节途径提供新的见解。

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.