Cichutek A, Brueckmann T, Seipel B, Hauser H, Schlaubitz S, Prawitt D, Hankeln T, Schmidt E R, Winterpacht A, Zabel B U
Department of Pediatrics, University of Mainz, Mainz, Germany.
Cytogenet Cell Genet. 2001;93(3-4):277-83. doi: 10.1159/000056998.
Human chromosome 11p15.3 is associated with chromosome aberrations in the Beckwith Wiedemann Syndrome and implicated in the pathogenesis of different tumor types including lung cancer and leukemias. To date, only single tumor-relevant genes with linkage to this region (e.g. LMO1) have been found suggesting that this region may harbor additional potential disease associated genes. Although this genomic area has been studied for years, the exact order of genes/chromosome markers between D11S572 and the WEE1 gene locus remained unclear. Using the FISH technique and PAC clones of the flanking markers we determined the order of the genomic markers. Based on these clones we established a PAC contig of the respective region. To analyse the chromosome area in detail the synteny of the orthologous region on distal mouse chromosome 7 was determined and a corresponding mouse clone contig established, proving the conserved order of the genes and markers in both species: "cen-WEE1-D11S2043-ZNF143-RANBP7-CEGF1- ST5-D11S932-LMO1-D11S572-TUB-tel", with inverted order of the murine genes with respect to the telomere/centromere orientation. The region covered by these contigs comprises roughly 1.6 MB in human as well as in mouse. The genomic sequence of the two subregions (around WEE1 and LMO1) in both species was determined using a shotgun sequencing strategy. Comparative sequence analysis techniques demonstrate that the content of repetitive elements seems to decline from centromere to telomere (52.6% to 34.5%) in human and in the corresponding murine region from telomere to centromere (41.87% to 27.82%). Genomic organisation of the regions around WEE1 and LMO1 was conserved, although the length of gene regions varied between the species in an unpredictable ratio. CpG islands were found conserved in putative promoter regions of the known genes but also in regions which so far have not been described as harboring expressed sequences.
人类染色体11p15.3与贝克威思-维德曼综合征中的染色体畸变相关，并与包括肺癌和白血病在内的不同肿瘤类型的发病机制有关。迄今为止，仅发现了与该区域连锁的单个肿瘤相关基因（例如LMO1），这表明该区域可能含有其他潜在的疾病相关基因。尽管该基因组区域已经研究多年，但D11S572和WEE1基因座之间基因/染色体标记的确切顺序仍不清楚。我们使用FISH技术和侧翼标记的PAC克隆确定了基因组标记的顺序。基于这些克隆，我们建立了相应区域的PAC重叠群。为了详细分析染色体区域，我们确定了小鼠远端染色体7上同源区域的同线性，并建立了相应的小鼠克隆重叠群，证明了两个物种中基因和标记的保守顺序：“着丝粒-WEE1-D11S2043-ZNF143-RANBP7-CEGF1-ST5-D11S932-LMO1-D11S572-微管-端粒”，其中小鼠基因相对于端粒/着丝粒方向的顺序是颠倒的。这些重叠群覆盖的区域在人类和小鼠中大致都为1.6兆字节。使用鸟枪法测序策略确定了两个物种中两个子区域（WEE1和LMO1周围）的基因组序列。比较序列分析技术表明，人类中重复元件的含量似乎从着丝粒到端粒逐渐下降（52.6%至34.5%），而在相应的小鼠区域中则从端粒到着丝粒逐渐下降（41.87%至27.82%）。WEE1和LMO1周围区域的基因组组织是保守的，尽管基因区域的长度在不同物种之间以不可预测的比例变化。在已知基因的推定启动子区域以及迄今为止尚未被描述为含有表达序列的区域中都发现了保守的CpG岛。
