GEN BD

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。自1988年以来，NIMH遗传学倡议一直支持双相情感障碍（BP）研究的国家资源。到1997年，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。现在这是一个公开的资源，分析结果已经发表。1998年开始了第二次努力，以确定500对新的BP兄弟姐妹；这一目标已经超过了523对额外的BPI兄弟姐妹确定，采访，并收集了DNA样本。遗传疾病研究中心（CIDR）对237对兄弟姐妹家庭完成了全基因组扫描；其余309个家族将在2003年通过CIDR进行基因分型。该资源是同类资源中最大的，已经揭示了染色体6q和17q上连锁区域的证据。它还证实了染色体22q上的一个位点，并支持了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。我们建议扩展国家遗传资源，包括5000个不相关的BP先证者和2000个父母样本，作为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（先前参与的10个地点加上霍华德大学，该大学将提供额外的非裔美国人先证者）确定和评估。该样本将成为连锁区域内精细尺度连锁不平衡定位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的控制。生物信息学技术将发展并支持候选区域的基因组分析，以帮助选择snp和其他多态性标记和引物设计。基因分型将在8个实验室间协调，采用知情的分步方法，首先对目前699个家系进行标准微卫星定位，然后在一个工业实验室进行单核苷酸多态性的合同基因分型，接着在各个地点的实验室进行后续区域基因分型和相关基因测序。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。对现有的兄弟姐妹家庭进行分析，加上这一大批病例和对照，应该可以确认在这一资助期间的几个易感基因。

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.