Mapping and Gene Content of the Mouse t-complex

小鼠 t 复合物的定位和基因内容

• 批准号: 6097860
• 负责人: Ramaiah Nagaraja
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6097860
• 关键词: CpG islands; computer assisted sequence analysis; developmental genetics; gene expression; genetic mapping; genomic imprinting; lethal genes; molecular cloning; nucleic acid repetitive sequence; nucleic acid sequence

The mouse t-complex on chromosome 17 has long been a focus of interest for developmental biologists. Because many embryonic lethal mutations are localized in the region, and corresponding genes of importance in development are therefore inferred to reside there, it is a prime target for high priority sequence analysis. The findings of our collaborators that the region contains a large number of otherwise unknown genes, including many expressed selectively in the ectoplacental cone, both underlines the importance of the region and provides probes to screen for substrates for long-range sequence analysis. We have thus started to analyze a multimegabase portion of the t- complex. From the initially targeted 1 Mb of overlapping bacterial artificial chromosomes, the sequencing of one 175 kb clone has been completed with greater than 99.9% accuracy. Because very little mouse genomic sequence is available, the analysis must bootstrap from several starting sources. The analysis is therefore incomplete, but the results are encouraging. Our main tools for the analysis are the GENBANK EST database, the exon- predicting program GRAIL, the repetitive sequence finding program CENSOR, and the use of CpG content as an assay for CpG islands and genes. Thus far, four genes have been identified and verified, including the nown gene for ALS 9 which binds and stabilizes the IGF/IGFBP3 complex in serum), the round sperm gene (RSP29), and two newly discovered genes, one of which shows significant sequence to a human nucleotide-binding protein. CpG islands and other EST hits extend the likely catalogue to up to 11 genes in the DNA. This would yield an average of 1 gene/ 15 kb, making this zone of the t-complex part of the highest gene density fraction (2 to 5%) of the genome.

17号染色体上的小鼠t复合体 一直是发育生物学家关注的焦点。因为很多 胚胎致命突变位于该区域， 因此，在发育中重要的相应基因是 据推测，它居住在那里，这是一个高优先级的主要目标， 序列分析我们的合作者发现， 含有大量其他未知基因，包括 许多选择性表达于胎盘外锥， 强调了该地区的重要性，并提供了探测器， 筛选用于长距离序列分析的底物。我们有 从而开始分析T-复合体的数百万个部分。 从最初靶向的1 Mb重叠细菌人工 染色体，一个175 kb克隆的测序已经完成。 准确率超过99.9%。因为几乎没有 小鼠基因组序列可用，分析必须自举 从几个源头开始。因此，分析是不完整的， 但结果令人鼓舞。我们的主要分析工具是 GENBANK EST数据库，外显子预测程序 GRAIL，重复序列发现程序CENSOR，以及 使用CpG含量作为CpG岛和基因的测定。因此 迄今为止，已经鉴定和验证了四个基因，包括已知的 结合并稳定IGF/IGFBP 3的ALS 9基因 复杂的血清），圆形精子基因（RSP 29），和两个新的 发现的基因，其中一个显示出显着的序列， 人核苷酸结合蛋白。CpG岛和其他EST命中 将可能的目录扩展到DNA中的11个基因。这 将产生平均1个基因/ 15 kb，使该区域的 最高基因密度分数（2至5%）的t-复合体部分 基因组