Deep Sequencing in Schizophrenia

精神分裂症的深度测序

• 批准号: 8812721
• 负责人: Debby Wen Tsuang
• 金额: --
• 依托单位: VA PUGET SOUND HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8812721
• 关键词: Accounting; Adoption; Adult; Affect; Behavior; Bioinformatics; Biological; Cataloging; Catalogs; Cell model; Code; Complex; Computer Simulation; Copy Number Polymorphism; Data; Delusions; Development; Disease; Disease susceptibility; Emotions; Environment; Etiology; Exons; Experimental Models; Family; Functional disorder; Funding; Funding Mechanisms; Genes; Genetic; Genetic Predisposition to Disease; Genetic study; Genome; Genome Scan; Genotype; Hallucinations; Hereditary Disease; Human; Human Genome; Individual; Influentials; Inherited; Knowledge; Lead; Life; Mental disorders; Methods; Molecular; Molecular Genetics; Morbidity - disease rate; National Institute of Mental Health; Nucleotides; Open Reading Frames; Outcome; Pathogenesis; Pathway interactions; Penetrance; Phenotype; Predisposition; Prevention therapy; Research; Research Personnel; Sampling; Schizophrenia; Sequence Alignment; Speech; Staging; Susceptibility Gene; Symptoms; System; Technology; Twin Multiple Birth; Validation; Variant; Veterans; animal model development; base; computerized data processing; cooperative study; deep sequencing; design; disorder prevention; disorder risk; exome; exome sequencing; experience; follow-up; genetic association; genetic linkage; genetic linkage analysis; genetic pedigree; genetic variant; genome sequencing; genome wide association study; high risk; identity by descent; improved; interest; mortality; new therapeutic target; next generation sequencing; novel; novel strategies; prevent; programs; public health relevance; rare variant; research study; risk variant; symptom management; targeted sequencing; transmission process

DESCRIPTION (provided by applicant): Schizophrenia is a lifelong illness that is characterized by hallucinations, delusions, disorganized speech, grossly disorganized behavior, and negative symptoms. Although family, twin, and adoption studies have consistently demonstrated a genetic etiology for schizophrenia, no causative genes have yet been identified. Therefore, it is crucial that we pursue an increased understanding of the underlying etiology of schizophrenia. The identification of genetic susceptibility factors in schizophrenia represents a critical step toward detecting presymptomatic individuals who are at high risk for developing the disease, designing novel therapeutic targets to decrease associated morbidity and mortality, and ultimately, preventing the disorder. With new advances in technology, more powerful approaches have emerged. One of these new approaches, called "next-generation sequencing," is a method that can detect all of the genetic sequence variants in a genome. Although sequencing every one of the three billion nucleotides that is present in the human genome is possible, it is not financially feasible to sequence the genomes of a large number of individuals, particularly because the necessary computational and bioinformatics data processing methods for whole-genome sequencing are still under development. Alternatively, the human exome contains all of the exons or coding regions in a genome (~5 Mb), and it is believed that the exome harbors much of the functional variation in humans. These recent advances set the stage for the kinds of comprehensive analysis that are necessary to identify underlying rare genetic variants, particularly in regard to family-based samples, which are the focus of this proposal. Whole exome and targeted sequence data, including data related to noncoding regions, now provide the opportunity to perform comprehensive analyses that will identify schizophrenia susceptibility genes in family-based samples. We hypothesize that the identification and analysis of rare inherited variants in families with schizophrenia will contribute to our understanding of the biological pathways that underlie schizophrenia. Specifically, we hypothesize that rare variants with relatively high penetrance will be important in familial schizophrenia pedigrees selected from the Veterans Affairs Cooperative Study Program #366 and National Institute of Mental Health Genetic Initiative on Schizophrenia. Our interdisciplinary group of investigators anticipates that we can identify these rare variants using novel analytic approaches, next- generation sequencing, and publicly available bioinformatics information. Although individually rare, these higher-penetrance forms of schizophrenia will lead to an improved understanding of the genetic and molecular basis of schizophrenia. Knowledge of these risk genes will facilitate exploration of the pathogenesis of schizophrenia at a molecular level and the development of animal and cellular models for the disease. Such research endeavors will significantly advance the search for treatments for schizophrenia.

描述（由申请人提供）：