GEN BD

基因BD

• 批准号: 7607818
• 负责人: WILLIAM Bradford LAWSON
• 金额: $ 15.46万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7607818
• 关键词: 10p; 13q; 16p; 17q; 21q; 22q; African American; Area; Bioinformatics; Bipolar Disorder; Cell Line; Chromosomes; Clinical Data; Computer Retrieval of Information on Scientific Projects Database; Contracts; DNA; Data Linkages; Disease; Family; Funding; Genes; Genetic; Genomics; Genotype; Goals; Grant; Individual; Inherited; Institution; Interview; Laboratories; Linkage Disequilibrium; Maps; National Institute of Mental Health; Parents; Polymorphic Microsatellite Marker; Publishing; Research; Research Personnel; Resources; SNP genotyping; Sampling; Site; Source; Standards of Weights and Measures; Stratification; Techniques; United States National Institutes of Health; Universities; base; case control; design; follow-up; genetic pedigree; genetic resource; genome wide association study; proband

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Since 1988 the NIMH Genetics Initiative has supported a national resource for the study of bipolar disorder (BP). By 1997 153 multiplex families were assessed, providing cell lines, DNA, and anonymized clinical data. This is now a publicly available resource and analytic results have been published. A second effort commenced in 1998 to ascertain 500 new BP sib pairs; this goal has been exceeded with 523 additional BPI sib pairs ascertained, interviewed, and a DNA sample collected. A genome wide scan has been completed at the Center for Inherited Disease Research (CIDR) on 237 sib pair families; the remaining 309 families will be genotyped by CIDR during 2003. This resource, the largest of its kind, has revealed evidence for area of linkage on chromosomes 6q and 17q. It has also provided confirmation of a locus on chromosome 22q and support for areas on 1p, 10p, 16p, 13q, and 21q. Accumulating linkage data has implicated other chormosomal regions. We propose an extension of the national genetic resource to include a sample of 5000 unrelated BP probands and 2000 parents for case-control and family-based association resource. Probands and parents will be ascertained and assessed at eleven sites (the ten sites previously participating plus Howard University, which will provide additional African-American probands). This sample will be a national resource for fine scale linkage disequilibrium mappping within regions of linkage, as well as condidate gene association studies. Parental DNAs in a subsample will allow additional control for ethnic stratification. Bioinformatics techniques will be developed and supported for genomic analysis of condidate regions, to assist selection of SNPs and other polymorphic markers and primer design. The genotyping will be coordinated across 8 labs with an informed step-wise approach, beginning with standard micro-satellite mapping of the current set of 699 pedigrees, followed by contract genotyping of SNPs in an industrial laboratory, and continuing with follow-up genotyping of regions and sequencing of associated genes in laboratories at the individual sites. SNP typing of the larger case-control sample will occur primarily in the final year of the collaborative study. Analysis of the existing sib pair families plus this large set of cases and controls should permit the confirmation of several vulnerability genes during this grant period.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 自 1988 年以来，NIMH 遗传学计划一直支持双相情感障碍 (BP) 研究的国家资源。 到 1997 年，我们对 153 个多重家族进行了评估，提供了细胞系、DNA 和匿名临床数据。 该资源现已成为公开资源，分析结果也已发布。 第二次工作于 1998 年开始，以确定 500 个新的 BP 同胞对；通过对另外 523 个 BPI 同胞对进行查明、访谈并收集 DNA 样本，已经超出了这一目标。 遗传病研究中心 (CIDR) 已完成对 237 个同胞对家族的全基因组扫描； CIDR 将在 2003 年对其余 309 个家族进行基因分型。这一资源是同类资源中规模最大的，已揭示了染色体 6q 和 17q 上连锁区域的证据。 它还确认了染色体 22q 上的基因座，并支持 1p、10p、16p、13q 和 21q 上的区域。 积累的连锁数据暗示了其他染色体区域。 我们建议扩大国家遗传资源，纳入 5000 名无关 BP 先证者和 2000 名父母的样本，用于病例对照和家庭协会资源。 先证者和父母将在十一个地点进行确定和评估（之前参与的十个地点加上霍华德大学，霍华德大学将提供更多的非裔美国先证者）。 该样本将成为连锁区域内精细连锁不平衡图谱以及候选基因关联研究的国家资源。 子样本中的亲本 DNA 将允许对种族分层进行额外控制。 将开发并支持生物信息学技术，用于候选区域的基因组分析，以协助选择 SNP 和其他多态性标记以及引物设计。 基因分型将在 8 个实验室之间采用明智的逐步方法进行协调，首先对当前 699 个谱系进行标准微卫星测绘，然后在工业实验室中对 SNP 进行合同基因分型，并继续进行后续基因分型在各个地点的实验室中对相关基因进行区域和测序。 较大病例对照样本的 SNP 分型将主要在合作研究的最后一年进行。 对现有同胞对家庭的分析加上这一大组病例和对照应该可以在本资助期间确认几个易受攻击的基因。