Niederführ A, Hummerich H, Gawin B, Boyle S, Little P F, Gessler M
Physiologische Chemie I, Theodor-Boveri-Institut für Biowissenschaften der Universität Würzburg, Am Hubland, Würzburg, D-97074, Germany.
Genomics. 1998 Oct 15;53(2):155-63. doi: 10.1006/geno.1998.5486.
A large body of evidence that links alterations of chromosome 11p13 to tumor formation and various developmental disorders has been accumulated. To address the underlying genetic events it would be helpful to have a comprehensive gene map of the region, and this is most readily achieved by generating the complete genomic sequence. Building upon previous mapping and YAC contig analysis we have established a 3-Mb sequence-ready PAC contig. It was constructed by chromosome walking and independently verified by fingerprint analysis of individual clones. The contig starts from the catalase gene on the centromeric side and reaches beyond the PAX6 gene at the 11p13/p14.1 boundary. Additional smaller contigs on either side were identified, but still have to be linked up. The 3-Mb contig spans the central region of deletions encompassing 16 chromosomal breakpoints in patients with WAGR syndrome (Wilms tumor, aniridia, genitourinary malformation, mental retardation), and its construction is an important step in facilitating functional analysis of these genes.
大量证据表明，11p13染色体的改变与肿瘤形成和各种发育障碍有关。为了探究潜在的遗传事件，绘制该区域完整的基因图谱将有所帮助，而生成完整的基因组序列最容易实现这一点。基于先前的图谱绘制和酵母人工染色体（YAC）重叠群分析，我们构建了一个3兆碱基（Mb）的可用于测序的细菌人工染色体（PAC）重叠群。它通过染色体步移构建而成，并通过对单个克隆的指纹分析进行独立验证。该重叠群从着丝粒一侧的过氧化氢酶基因开始，延伸至11p13/p14.1边界处的PAX6基因之外。在两侧还鉴定出了其他较小的重叠群，但仍需连接起来。这个3-Mb的重叠群跨越了缺失的中心区域，该区域包含WAGR综合征（威尔姆斯瘤、无虹膜、泌尿生殖系统畸形、智力迟钝）患者的16个染色体断点，其构建是促进这些基因功能分析的重要一步。
