Sait S N, Nowak N J, Singh-Kahlon P, Weksberg R, Squire J, Shows T B, Higgins M J
Department of Human Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263.
Genes Chromosomes Cancer. 1994 Oct;11(2):97-105. doi: 10.1002/gcc.2870110206.
Chromosome rearrangements have provided useful landmarks to identify disease loci and have served as starting points for positional cloning strategies for candidate genes. We have used fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to map three Beckwith-Wiedemann syndrome (BWS) breakpoints and a rhabdoid tumor breakpoint more precisely. These breakpoints mapped to the interval between D11S679 and the insulin-like growth factor 2 (IGF2) gene on 11p15.5. A cosmid (c15-2) was identified that mapped centromeric to the BWS t(11;16) and the rhabdoid tumor-associated t(11;22), telomeric to the BWS t(11;22), and was found to span the BWS-associated inv(11) breakpoint. Pulsed-field gel analysis placed all four breakpoints into a 250-675 kb interval distal to D11S679 and at least 270 kb centromeric to the IGF2 and H19 loci. These data locate all three BWS rearrangements and the rhabdoid tumor t(11;22) breakpoint in the same region of 11p15.5, suggesting that they may be affecting the same locus or closely linked loci. Cosmid c15-2 provides a well-defined starting point in the search for candidate disease genes.
染色体重排为识别疾病基因座提供了有用的标记，并作为候选基因定位克隆策略的起点。我们使用荧光原位杂交（FISH）和脉冲场凝胶电泳（PFGE）更精确地定位了三个贝克威思-维德曼综合征（BWS）断点和一个横纹肌肉瘤断点。这些断点定位于11p15.5上D11S679和胰岛素样生长因子2（IGF2）基因之间的区间。鉴定出一个粘粒（c15-2），它定位于BWS t(11;16)和与横纹肌肉瘤相关的t(11;22)的着丝粒侧、BWS t(11;22)的端粒侧，并发现它跨越了与BWS相关的inv(11)断点。脉冲场凝胶分析将所有四个断点置于D11S679远端250-675 kb的区间内，且在IGF2和H19基因座的着丝粒侧至少270 kb处。这些数据将所有三个BWS重排和横纹肌肉瘤t(11;22)断点定位在11p15.5的同一区域，表明它们可能影响同一个基因座或紧密连锁的基因座。粘粒c15-2为寻找候选疾病基因提供了一个明确的起点。
