GENETIC ANALYSIS AND CHARACTERIZATION OF IDDM GENES

这是大鼠基因组EST计划(RGP/EST)的续签申请。大鼠模型和该项目的继续具有重要意义，原因有几个。首先，RHP/EST的直接结果是鉴定了大量新基因(爱荷华州大学)。第二，在不同的大鼠模型中已经并正在定位大量数量性状。第三，大鼠仍然是学术界和工业界生物医学研究的主要模型，具有悠久的生理学、药理学和生物化学研究历史。第四，大鼠EST具有可识别的人类和/或物种，并将大鼠的生理学与小鼠的遗传学和人类的临床相关性联系起来。正如我们的进度报告所概述的那样，我们在RGP/EST方面取得了巨大进展。第五，RGP/EST将有助于加速发现与常见疾病有关的基因和途径，使已绘制数量性状基因座(QTL)图的研究人员能够直接或通过比较图谱与人类序列的额外链接来识别区间内的位置候选基因。我们已与爱荷华州大学集团联手，利用我们合并的现有基础设施绘制了27,000个额外的RAT EST(15,000个MCW+12,000 U的爱荷华州)。分工的目的是在不明显增加设备或人员数量的情况下，保持两个RH测绘团队的完整。虽然这种关系在这些续签申请中得到了正式确立，但我们从一开始就协调努力，共同努力。我们已开始开发“主干”地图，以提供综合地图的手段，促进比较地图绘制，并倡议实物地图的框架。这一主干建立在遗传标记和基因/EST的基础上，需要三个组成部分：绘制大量遗传标记(基本完成)和基因/EST，需要三个组成部分：绘制大量遗传标记(基本完成)和基因/EST，构建比较图谱，最后进行虚拟作图。我们将另外15,000个具有序列同源性的EST映射到已经映射的人类和小鼠基因/EST。联合的努力(爱荷华州的MCW和U)将导致所有大鼠基因的三分之一以上被定位并放置在RH“主干”图谱上，以便于使用序列“挂钩”进行比较基因组学。

This is an application for the renewal for the Rat Genome EST Project (RGP/EST). The rat model and the continuation of this project is important for several reasons. First, a direct result of RHP/EST is a the identification of large numbers of novel genes (U of Iowa). Second, large numbers of quantitative traits have been and are being mapped in various rat models. Third, the rat remains a major model for biomedical research within both academia and industry, with a long history of physiological, pharmacological, and biochemical studies. Fourth, rat ESTs with identifiable human and/or species and link the physiology of the rat with the genetics of the mouse and the clinical relevance in the human. As outlined in our progress report, we have made tremendous strides in the RGP/EST. Fifth, RGP/EST will help to accelerate the discovery of genes and pathways involved in common disease by enabling investigators who have mapped quantitative trait loci (QTLs) to identify positional candidate genes within the intervals directly or through additional links to the human sequence via comparative mapping. We have joined forces with the UC of Iowa group to use our combined existing infrastructure to map 27,000 additional rat ESTs (15,000 MCW + 12,000 U of Iowa). The division of labor is designed to keep both RH mapping teams intact without markedly expanding equipment or numbers of personnel. While this relationship is formalized in these renewal applications, we have coordinated efforts and worked together from the start. We have initiated the development of a "Backbone" map to provide the means to integrate maps, to facilitate comparative mapping, and to initiative the framework for the physical map. This backbone, build on both genetic markers and genes/ESTs, requires three components: mapping large numbers of genetic markers (largely completed) and genes/ESTs, requires three components: mapping large numbers of genetic markers (largely completed) and genes/ESTs, constructing the comparative maps and finally virtual mapping. We will map an additional 15,000 ESTs with sequence homology to human and mouse genes/ESTs that have been mapped. The combined efforts (MCW and U of Iowa) will result in more 1/3 of all rat genes mapped and placed on the RH "Backbone" map facilitating comparative genomics with sequence "hooks".