Multi-Species Comparative Sequencing of Targeted Genomic

正在进行的人类基因组计划取得了令人印象深刻的成功，其中包括不断加快阐明各种生物体完整基因组序列的时间表。随着人类基因组序列的接近完成，其他脊椎动物基因组的测序正占据中心位置。最近启动的广泛研究的模式生物（如小鼠、大鼠和斑马鱼）的测序项目将为未来的实验提供宝贵的资源，并为脊椎动物生物学提供重要的见解。不太清楚的是其他候选基因组的相对价值，特别是关于它们对人类序列的注释和解释的潜在贡献。为了开始研究这些问题，我们正在从多个脊椎动物中生成大块的同源序列，以进行详细的比较分析。具体来说，从多个脊椎动物物种中分离出相同的目标基因组区域，然后对其进行测序。开发并实现了设计同源杂交探针和分离不同物种BAC克隆的有效方法。通过几种映射方法进行表征，然后选择bac的平铺路径并进行系统测序。总的来说，每年产生的比较测序数据为150 Mb。这一比较序列资源的建立将有助于开发用于多物种序列比较的新计算工具，为其他脊椎动物物种的测序提供合适的测序精加工程度，并揭示从不同进化距离对物种进行测序的好处。

The impressive successes of the ongoing Human Genome Project have included ever-accelerating timetables for elucidating the complete genomic sequence of various organisms. As the human genome sequence nears completion, the sequencing of other vertebrate genomes is taking center stage. The recent initiation of sequencing projects for widely studied model organisms (e.g., mouse, rat, and zebrafish) will provide a valuable resource for future experimentation and important insights into vertebrate biology. Less clear is the relative value of other candidate genomes being considered for systematic sequencing, especially with regard to their potential contribution to the annotation and interpretation of the human sequence. To begin investigating such issues, we are generating large blocks of orthologous sequence from multiple vertebrates for detailed comparative analyses. Specifically, the same targeted genomic regions from multiple vertebrate specie are being isolated in large-insert clones and then sequenced. Efficient methods for designing orthologous hybridization probes and isolating BAC clones from the different species have been developed and implemented. Following characterization by several mapping methods, tiling paths of BACs are then selected and systematically sequenced. In total, >150 Mb of comparative sequencing data is being generated each year. The establishment of this comparative sequence resource should facilitate the development of new computational tools for multi-species sequence comparisons, provide insight about the appropriate degrees of sequencing finishing that should be pursued in the sequencing of other vertebrate species, and reveal the benefits of sequencing species from a range of evolutionary distances.