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

点击翻译按钮获取中文摘要

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.