1/3 - Genomics of Schizophrenia in the South Africa Xhosa

描述(申请人提供)：这一国际合作项目的目标是在南非科萨族人口中识别导致精神分裂症的基因。三个参与网站分别是纽约哥伦比亚大学(Ezra Susser，PI)，西雅图华盛顿大学(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得到解释。我们假设，对精神分裂症重要的基因和途径将在不同的受影响个体中包含不同的、严重的致病突变。考虑到非洲人群的遗传多样性，我们希望找到其他人群研究中尚未出现的精神分裂症基因。该项目还将促进非洲神经精神障碍基因发现研究的发展。在1100名患有精神分裂症的科萨族人和1100名年龄和性别匹配的科萨族对照组中，我们将比较外显体、侧翼调控位点和非编码RNA(通过外显子组测序获得)和结构基因组变异(通过arrayCGH获得)的图谱。稀有/私有变异和古老的非洲等位基因都将被识别和评估。与对照组相比，精神分裂症患者体内有害突变丰富的基因将被定义为候选基因。候选基因的变异图谱将在来自其他人群精神分裂症研究的NIMH序列数据库中进行评估。该项目将首次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中的精神分裂症。如果成功，我们的方法将在世界各地的人群中识别导致这种疾病的重要基因。这些基因将刺激未来开发更有效的治疗和预防策略的努力。

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.