A 1-Mb physical map and PAC contig of the imprinted domain in 11p15.5 that contains TAPA1 and the BWSCR1/WT2 region.
A 1-Mb physical map and PAC contig of the imprinted domain in 11p15.5 that contains TAPA1 and the BWSCR1/WT2 region.
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DOI：
10.1006/geno.1997.4826
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发表时间：
1997-08
期刊：
影响因子：
4.4
通讯作者：
L. Reid;C. Davies;P. R. Cooper;S. J. Crider-Miller;S. Sait;N. Nowak;G. Evans;E. Stanbridge;P. Dejong;T. Shows;B. Weissman;M. Higgins
中科院分区：
文献类型：
--
作者：
L. Reid;C. Davies;P. R. Cooper;S. J. Crider-Miller;S. Sait;N. Nowak;G. Evans;E. Stanbridge;P. Dejong;T. Shows;B. Weissman;M. Higgins
我们已经在人类染色体11p15.5带上构建了一个1-Mb重叠群，该区域与包括Wilms瘤和Beckwith-Wiedemann综合征在内的几种胚胎肿瘤的病因学有关。用Noti/Sali双酶切鉴定COSMID、P1、PAC和BAC克隆，并与多种探针杂交，生成从D11S517到L23MRP的详细物理图谱。该图谱包括CARS、NAP2、p57/KIP2、KVLQT1、ASCL2、TH、INS、IGF2、H19和L23MRP基因，以及从PAC中分离的末端探针。TAPA1基因也定位在重叠群中，其蛋白产物可以传递抗增殖信号。然而，Northern印迹分析表明，TAPA1的表达与G401 Wilms肿瘤杂交瘤细胞的致瘤性无关，表明TAPA1不参与11p15.5相关的肿瘤抑制。以基因组克隆为探针进行FISH分析，定位3例Beckwith-Wiedemann综合征患者和1例横纹肌样瘤的断裂点。有趣的是，每个断裂点都破坏了KVLQT1基因，该基因分布在重叠群的400kb区域。由于11p15.5包含几个印记表达的基因和一个或多个肿瘤抑制基因，我们的重叠群和图谱为描述这种有趣的遗传环境提供了一个框架。
We have constructed a 1-Mb contig in human chromosomal band 11p15.5, a region implicated in the etiology of several embryonal tumors, including Wilms tumor, and in Beckwith-Wiedemann syndrome. Cosmid, P1, PAC, and BAC clones were characterized by NotI/SalI digestion and hybridized to a variety of probes to generate a detailed physical map that extends from D11S517 to L23MRP. Included in the map are the CARS, NAP2, p57/KIP2, KVLQT1, ASCL2, TH, INS, IGF2, H19, and L23MRP genes as well as end probes isolated from PACs. The TAPA1 gene, whose protein product can transmit an antiproliferative signal, was also localized in the contig. However, Northern blot analysis demonstrated that its expression did not correlate with tumorigenicity in G401 Wilms tumor hybrids, suggesting that TAPA1 is not responsible for the tumor suppression associated with 11p15.5. Genomic clones were used as probes in FISH analysis to map the breakpoints from three Beckwith-Wiedemann syndrome patients and a rhabdoid tumor. Interestingly, each of the breakpoints disrupts the KVLQT1 gene, which is spread over a 400-kb region of the contig. Since 11p15.5 contains several genes with imprinted expression and one or more tumor suppressor genes, our contig and map provide a framework for characterizing this intriguing genetic environment.