2/3 Genomics of Schizophrenia in the South African Xhosa

2/3 南非科萨人精神分裂症的基因组学

• 批准号: 9075382
• 负责人: MARY-CLAIRE KING
• 金额: $ 20.86万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-10 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9075382
• 关键词: Affect; Africa; African; Age; Alleles; Candidate Disease Gene; Code; Communities; Copy Number Polymorphism; Data; Databases; Development; Disease; Enrollment; Fostering; Frequencies; Future; Gender; Genes; Genetic; Genetic Variation; Genomic approach; Genomics; Goals; Health; Individual; International; Left; Mutation; National Institute of Mental Health; New York; Nucleic Acid Regulatory Sequences; Pathway interactions; Point Mutation; Population; Population Control; Prevention strategy; Research; Resources; Schizophrenia; Site; South Africa; Stratification; Universities; Untranslated RNA; Variant; Washington; Weight; base; case control; cohort; disease-causing mutation; effective therapy; exome; exome sequencing; gene discovery; genetic variant; genome-wide; insertion/deletion mutation; neuropsychiatry; rare variant; structural genomics; treatment strategy

DESCRIPTION (provided by applicant): The goal of this international collaborative project is to identify genes responsible for schizophrenia in the Xhosa population of South Africa. The three participating sites are Columbia University, New York (Ezra Susser, PI), University of Washington, Seattle (Mary- Claire King, Jack McClellan, Tom Walsh, MPIs), and University of Cape Town, South Africa (Dan Stein, PI). The vast majority of the genetic basis for schizophrenia has yet to be explained. We hypothesize that genes and pathways important to schizophrenia will harbor different, severe disease-causing mutations in different affected individuals. Given the genetic diversity of African populations, we expect to find genes for schizophrenia that have not yet emerged from studies of other populations. This project will also foster the development of gene discovery research for neuropsychiatric disorders in Africa. In 1100 Xhosa individuals with schizophrenia and 1100 age and gender-matched Xhosa controls, we will compare profiles of exomes, flanking regulatory sites, and noncoding RNAs (obtained by exome sequencing) and profiles of structural genomic variants (obtained by arrayCGH). Both rare/private variants and ancient African alleles will be identified and evaluated. Genes enriched for deleterious mutations in individuals with schizophrenia compared to controls will be defined as candidates. Variant profiles of candidate genes will be assessed in NIMH sequence databases derived from schizophrenia studies of other populations. This project will be the first to use modern genomic sequencing approaches to study schizophrenia in a population of sub-Saharan African lineage. If successful, our approach will identify genes important for the disorder in populations worldwide. These genes will stimulate future efforts to develop more effective treatment and prevention strategies.

描述（由申请人提供）：该国际协作项目的目标是确定南非Xhosa人口中负责精神分裂症的基因。这三个参与地点是纽约哥伦比亚大学（埃兹拉·苏瑟（Ezra Susser），PI），华盛顿大学，西雅图（Mary-Claire King，Jack McClellan，Tom Walsh，MPIS）和南非开普敦大学（Dan Stein，PI）。精神分裂症的绝大多数遗传基础尚未解释。我们假设对精神分裂症重要的基因和途径将在不同受影响的个体中具有不同的，严重的致病突变。鉴于非洲人群的遗传多样性，我们希望找到尚未从其他人群研究中出现的精神分裂症基因。该项目还将促进非洲神经精神疾病基因发现研究的发展。在1100个具有精神分裂症和1100年龄和性别匹配的Xhosa对照的XHOSA个体中，我们将比较外部，侧翼调节位点和非编码RNA的曲线（通过外显子组测序获得）和结构基因组变体的曲线（通过ArrayCGH获得）。稀有/私人变体和古代非洲等位基因都将得到识别和评估。与对照组相比，精神分裂症个体中富含有害突变的基因将定义为候选者。候选基因的变异谱将在来自其他人群的精神分裂症研究中得出的NIMH序列数据库中进行评估。该项目将是第一个使用现代基因组测序方法来研究撒哈拉以南非洲血统人群的精神分裂症。如果成功，我们的方法将确定对全球人群中疾病重要的基因。这些基因将刺激未来的努力，以制定更有效的治疗和预防策略。