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，其中包括不断加快的阐明各种生物体完整基因组序列的时间表。随着人类基因组测序接近完成，其他脊椎动物基因组的测序正占据中心舞台。最近启动了广泛研究的模式生物测序项目（例如，小鼠、大鼠和斑马鱼）将为未来的实验和对脊椎动物生物学的重要见解提供有价值的资源。不太清楚的是其他候选基因组被考虑用于系统测序的相对价值，特别是关于它们对人类序列的注释和解释的潜在贡献。为了开始调查这些问题，我们正在从多种脊椎动物中产生大量的正向同源序列，以进行详细的比较分析。具体而言，来自多个脊椎动物物种的相同靶向基因组区域在大插入克隆中分离，然后测序。已经开发并实施了用于设计正交杂交探针和从不同物种分离BAC克隆的有效方法。通过几种映射方法进行表征后，选择BAC的平铺路径并进行系统测序。总的来说，每年产生>150 Mb的比较测序数据。这种比较序列资源的建立应促进新的计算工具的开发，用于多物种序列比较，提供有关在其他脊椎动物物种的测序中应追求的适当程度的测序整理的见解，并揭示从一系列进化距离的物种测序的好处。

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.