The Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
Database (Oxford). 2013 May 31;2013:bat032. doi: 10.1093/database/bat032. Print 2013.
Model organisms are becoming increasingly important for the study of complex diseases such as type 1 diabetes (T1D). The non-obese diabetic (NOD) mouse is an experimental model for T1D having been bred to develop the disease spontaneously in a process that is similar to humans. Genetic analysis of the NOD mouse has identified around 50 disease loci, which have the nomenclature Idd for insulin-dependent diabetes, distributed across at least 11 different chromosomes. In total, 21 Idd regions across 6 chromosomes, that are major contributors to T1D susceptibility or resistance, were selected for finished sequencing and annotation at the Wellcome Trust Sanger Institute. Here we describe the generation of 40.4 mega base-pairs of finished sequence from 289 bacterial artificial chromosomes for the NOD mouse. Manual annotation has identified 738 genes in the diabetes sensitive NOD mouse and 765 genes in homologous regions of the diabetes resistant C57BL/6J reference mouse across 19 candidate Idd regions. This has allowed us to call variation consequences between homologous exonic sequences for all annotated regions in the two mouse strains. We demonstrate the importance of this resource further by illustrating the technical difficulties that regions of inter-strain structural variation between the NOD mouse and the C57BL/6J reference mouse can cause for current next generation sequencing and assembly techniques. Furthermore, we have established that the variation rate in the Idd regions is 2.3 times higher than the mean found for the whole genome assembly for the NOD/ShiLtJ genome, which we suggest reflects the fact that positive selection for functional variation in immune genes is beneficial in regard to host defence. In summary, we provide an important resource, which aids the analysis of potential causative genes involved in T1D susceptibility. Database URLs: http://www.sanger.ac.uk/resources/mouse/nod/; http://vega-previous.sanger.ac.uk/info/data/mouse_regions.html#Idd
模式生物在研究复杂疾病（如 1 型糖尿病（T1D））方面变得越来越重要。非肥胖型糖尿病（NOD）小鼠是 T1D 的实验模型，它是在类似于人类的过程中自发产生疾病的。对 NOD 小鼠的基因分析已经确定了大约 50 个疾病位点，这些位点以胰岛素依赖型糖尿病（Idd）命名，分布在至少 11 条不同的染色体上。总共，在 6 条染色体上的 21 个 Idd 区域，是 T1D 易感性或抗性的主要贡献者，被选中进行全序列测序和 Wellcome Trust Sanger 研究所注释。在这里，我们描述了从 289 个细菌人工染色体中生成 40.4 兆碱基对 NOD 小鼠的完成序列。手动注释确定了糖尿病敏感的 NOD 小鼠中的 738 个基因和糖尿病抗性 C57BL/6J 参考小鼠同源区域中的 765 个基因，跨越 19 个候选 Idd 区域。这使得我们能够在两个小鼠品系的所有注释区域中调用同源外显子序列之间的变异后果。我们通过说明 NOD 小鼠和 C57BL/6J 参考小鼠之间的品系间结构变异区域对当前下一代测序和组装技术造成的技术困难，进一步证明了这一资源的重要性。此外，我们已经确定，Idd 区域的变异率比 NOD/ShiLtJ 基因组的全基因组组装的平均变异率高 2.3 倍，这表明了对免疫基因功能变异的正向选择有利于宿主防御的事实。总之，我们提供了一个重要的资源，有助于分析与 T1D 易感性相关的潜在致病基因。数据库网址：http://www.sanger.ac.uk/resources/mouse/nod/; http://vega-previous.sanger.ac.uk/info/data/mouse_regions.html#Idd
