GENETIC ANALYSIS AND CHARACTERIZATION OF IDDM GENES

这是大鼠基因组EST计划（RGP/EST）的更新申请。大鼠模型和该项目的继续是重要的，原因有几个。首先，RHP/EST的直接结果是鉴定出大量新基因（U of爱荷华州）。第二，大量的数量性状已经并正在绘制在各种大鼠模型。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，具有可识别的人类和/或物种的大鼠EST，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述，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，使已经绘制了数量性状基因座（QTL）的研究人员能够直接或通过比较作图与人类序列的额外链接来确定间隔内的位置候选基因。我们已经与爱荷华州的加州大学合作，使用我们现有的基础设施来绘制27，000个额外的大鼠EST（15，000个MCW +12，000个爱荷华州的U）。劳动分工的目的是保持两个RH测绘团队的完整性，而不会显着增加设备或人员数量。虽然这种关系在这些续约申请中得到了正式确认，但我们从一开始就协调努力并共同努力。我们已开始开发“主干”地图，以提供整合地图的手段，促进比较绘图，并为实物地图的框架提出倡议。这一主干，建立在遗传标记和基因/EST，需要三个组成部分：定位大量的遗传标记（大部分已完成）和基因/EST，需要三个组成部分：定位大量的遗传标记（大部分已完成）和基因/EST，构建比较图，最后虚拟定位。我们将绘制另外15，000个与已绘制的人类和小鼠基因/EST具有序列同源性的EST。联合努力（MCW和U of爱荷华州）将导致所有大鼠基因的1/3以上被定位并放置在RH“骨干”图谱上，从而促进具有序列“钩”的比较基因组学。

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".