HIGH RESOLUTION GENETIC ANALYSIS OF COMPLEX GENOMES

这项提议的目的既是生物的，也是技术的。这个 生物学目标与20-30岁的详细基因组分析有关 人和小鼠同源框复合体基因座周围的CM区域 染色体7/17和6/11。我们认为HOX-L和HOX-2基因座在 人类7号和17号染色体是部分同源的，代表着一种 大范围的复制发生在 人类和老鼠的血统是60-70年前的。我们进一步假设，许多 同源异型盒基因座附近的基因可能在功能上 并且这些领域可能协调发展 以及其他生物过程。 该项目的技术目标集中在开发 这些方法将共同加快基因组分析速度一个因素 五到十倍。这些将包括：(1)设计新的 可克隆细菌160bp插入片段的克隆载体 宿主和酵母宿主中的兆库范围内，(2)设计和 将允许现场特定的化学试剂的合成 双链DNA的断裂；(3)双链DNA的发育 高分辨率物理和孟德尔基因的综合方法 测绘方法。 总而言之，我们相信这一综合项目将 为当前的生物医学问题提供新的见解 意义，并贡献新的方法，将 大大增强了我们分析复杂基因组的能力，两者 在速度和分辨率的萌芽中。

The aims of this proposal are both biological and technical. The biological goals relate to detailed genomic analysis of the 20-30 cM regions surrounding the homeobox complex loci on human and mouse chromosomes 7/17 and 6/11. We believe the Hox-l and Hox-2 loci on human chromosomes 7 and 17 are parologous and represent an extensive duplication which occurred before the divergence of the human and mouse lineages 60-70 My ago. We further posit that many genes in the vicinity of the homeobox loci maybe functionally interrelated and that these domains may coordinate developmental and other biological processes. The technical aims of this project focus on the development of methods that will together speed up genomic analysis by a factor of five to ten fold. These will include (1) the design of new cloning vectors capable of cloning inserts of 160 bp in bacterial hosts and in the megabase range in yeast hosts, (2) the design and synthesis of chemical reagents which will permit the site specific scission of double stranded DNA, and (3) the development of integrated methods of high resolution physical and Mendelian gene mapping methods. In sum, we believe this integrated ensemble of projects will provide new insights into current biomedical problems of significance, and to contribute new methodologies which will substantially enhance our ability to analyze complex genomes, both in germs of speed and resolution.