GEN BD

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。自1988年以来，NIMH遗传学倡议一直支持一个研究双相情感障碍(BP)的国家资源。到1997年，对153个多基因家系进行了评估，提供了细胞系、DNA和匿名的临床数据。这现在是一个公开可用的资源，分析结果已经公布。1998年开始了第二项工作，以确定500个新的BP同胞对；这一目标已经超过了这一目标，确定了另外523个BPI同胞对，进行了访谈，并收集了DNA样本。遗传病研究中心(CIDR)已经完成了对237个同胞对家庭的全基因组扫描；其余309个家庭将在2003年期间通过CIDR进行基因分型。这是同类资源中最大的，揭示了6q和17q染色体上连锁区域的证据。它还证实了染色体22q上的一个基因座，并支持1p、10p、16p、13q和21q上的区域。随着连锁数据的积累，还发现了其他的染色体区域。我们建议扩大国家遗传资源的范围，包括5000名无血缘关系的BP先证者和2000名父母的样本，用于病例对照和基于家庭的关联资源。先证者和父母将在11个地点进行确定和评估(之前参与的10个地点加上霍华德大学，该大学将提供更多的非裔美国人先证者)。该样本将成为在连锁区域内进行精细连锁不平衡作图以及条件性基因关联研究的全国性资源。子样本中的父母DNA将允许对种族分层进行额外的控制。生物信息学技术将被开发和支持用于条件区域的基因组分析，以帮助选择SNPs和其他多态标记和引物设计。将以知情的循序渐进的方法协调8个实验室的基因分型工作，首先对当前的699个家系进行标准微卫星图谱绘制，然后在一个工业实验室对SNPs进行合同基因分型，然后在各个地点的实验室对区域进行后续基因分型和相关基因测序。较大的病例对照样本的SNP分型将主要在合作研究的最后一年进行。对现有同胞配对家庭的分析，加上这一大组病例和对照，应该能够在这一赠款期间确认几个易受感染的基因。

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.