Still I H, Roberts T, Cowell J K
Department of Neurosciences NC30, Cleveland Clinic Foundation, Ohio 44195, USA.
Ann Hum Genet. 1997 Jan;61(Pt 1):15-24. doi: 10.1046/j.1469-1809.1997.6110015.x.
Through linkage analysis and the identification of structural chromosome rearrangements, a number of disease genes have been mapped to the pericentromeric region of the long arm of chromosome 13. Structural rearrangements, or deletions, of the 13q12 region have been implicated in a range of myeloproliferative neoplasms, and other haematopoietic malignancies. In particular, seven cases of a t(8;13)(p11;q12.1) rearrangement have been noted in patients with an atypical myeloproliferative disorder associated with T-cell leukemia and eosinophilia. We have previously identified a CEPH mega YAC, 943E4, which crosses the translocation breakpoint in archival tumour samples from two patients with this t(8;13) translocation. As an initial step in the characterisation of this translocation breakpoint, we have generated a fine structure physical map of this 1.9 Mb YAC. We have used the method of YAC fragmentation to generate a series of deletion constructs of known size, which provide discreet physical landmarks convenient for mapping genetic markers along the 943E4 YAC. Analysis of these deletion constructs defined the order of ESTs and microsatellite markers in 943E4 as: cen-NIB1257-(ATP1AL1/D13S283)-D13S179E-(D13S5 04E/D13S505E)-D13S824E-D13S182E -D13S221-tel. These markers have also been assigned to physically defined regions relative to the fragmented YAC endpoints and a derived NotI restriction map.
通过连锁分析和结构染色体重排的鉴定，许多疾病基因已被定位到13号染色体长臂的着丝粒周围区域。13q12区域的结构重排或缺失与一系列骨髓增殖性肿瘤及其他造血系统恶性肿瘤有关。特别是，在患有与T细胞白血病和嗜酸性粒细胞增多相关的非典型骨髓增殖性疾病的患者中，已发现7例t(8;13)(p11;q12.1)重排。我们之前鉴定出一个CEPH大型酵母人工染色体（YAC）943E4，它跨越了两名患有这种t(8;13)易位的患者存档肿瘤样本中的易位断点。作为表征此易位断点的第一步，我们构建了这个1.9 Mb YAC的精细结构物理图谱。我们使用YAC片段化方法生成了一系列已知大小的缺失构建体，这些构建体提供了离散的物理标记，便于沿943E4 YAC定位遗传标记。对这些缺失构建体的分析确定了943E4中EST和微卫星标记的顺序为：着丝粒-NIB1257-(ATP1AL1/D13S283)-D13S179E-(D13S504E/D13S505E)-D13S824E-D13S182E -D13S221-端粒。相对于片段化YAC端点和衍生的NotI限制图谱，这些标记也已被定位到物理定义的区域。
