Molecular characterization of the 1p22 breakpoint region spanning the constitutional translocation breakpoint in a neuroblastoma patient with a t(1;10)(p22;q21)
Molecular characterization of the 1p22 breakpoint region spanning the constitutional translocation breakpoint in a neuroblastoma patient with a t(1;10)(p22;q21)
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DOI：
10.1016/s0165-4608(97)00013-7
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发表时间：
1998-01-01
影响因子：
--
通讯作者：
Cowell, JK
中科院分区：
文献类型：
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作者：
Roberts, T;Chernova, O;Cowell, JK
为了描述神经母细胞瘤患者的结构重排断点，我们在染色体1p22区域构建了一个酵母人工染色体（YAC），该染色体延伸约6 Mbp，横跨D1S435和D1S236位点。在不同重叠的YACs中，许多标记的重合证实了这一组合。在对产生STS标记的末端克隆进行分离和测序后，发现其中一些YACs存在重叠。通过体细胞杂交分析或荧光原位杂交，大多数YACs都显示不嵌合。在建立该序列之后，我们已经能够构建包含6个STS和3个新分配的eSTS标记的区域物理图谱。这个物理图谱的产生使得1p基因连锁图谱中的标记重新排序成为可能。物理秩序是；tel-D1S435-D1S188-D1S424-D1S236-D1D415-D1S420。通过对D1S435的重新排序，我们已经能够将该序列与之前报道的另一个序列连接起来，从而在1p22-31区域产生了一个表征良好的15 Mbp的YAC序列。这里描述的6mbp序列跨越了1号染色体的构象易位断点，见于患有t(1;10)（p22;q21）的4S期神经母细胞瘤患者。YAC碎片被用来定义包含1p22断点的200 Kb区域。限制性内切酶分析表明，该区域存在3个NotI位点，其中一个位于易位断点位点附近。(C) Elsevier Science Inc., 1998。
To characterize the breakpoint in a neuroblastoma patient with a constitutional rearrangement we have constructed a yeast artificial chromosome (YAC) contig extending approximately 6 Mbp in the chromosome 1p22 region that spans the D1S435 and D1S236 loci. This contig has been confirmed by the coincidence of a number of markers in different overlapping YACs. For several of these YACs the overlap was demonstrated following the isolation and sequencing of end clones from which STS markers were generated. The majority of the YACs have been shown not to be chimeric ic either through the analysis of somatic cell hybrids or fluorescence in situ hybridization, Following the establishment of the contig we have been able to construct a physical map of the region that incorporates six STS and three newly assigned eSTS markers. The generation of this physical map has allowed the reordering of markers in the genetic linkage map for 1p. The physical order is; tel-D1S435-D1S188-D1S424-D1S236-D1D415-D1S420. With the reordering of D1S435 we have been able to join this contig with another reported previously, thereby generating a well characterized 15 Mbp YAC contig in the 1p22-31 region. The 6 Mbp contig described here spans the chromosome 1 constitutional translocation breakpoint seen in a patient with a t(1;10)(p22;q21) and who had a stage 4S neuroblastoma. YAC fragmentation has been used to define a 200 Kb region within this contig containing the 1p22 breakpoint. Restriction enzyme analysis demonstrates that there are three NotI sites in this region, one of which lies close to the translocation breakpoint site. (C) Elsevier Science Inc., 1998.