Buiting K, Gross S, Ji Y, Senger G, Nicholls R D, Horsthemke B
Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany.
Cytogenet Cell Genet. 1998;81(3-4):247-53. doi: 10.1159/000015039.
Approximately 70% of patients with Prader-Willi syndrome or Angelman syndrome have a similar sized de novo deletion of 3-4 Mb in the proximal region of 15q. The distal breakpoints appear to cluster between the P gene (OCA2) and D15S24, whereas two deletion breakpoint clusters have been identified on the proximal side (one centromeric to D15S541 and one between D15S541 and D15S9). Based on the identification of a gene family in 15q11-->q13 (MN7, D15F37), we have previously proposed that the presence of multiple copies of this sequence may be related to the instability of this region. Using fluorescence in situ hybridization and YAC mapping, we have found that at least one D15F37 locus is centromeric to D15S9 and at least two are between OCA2 and D15S24. As determined by cDNA cloning and sequence analysis, each of the individual loci is expressed. The close proximity of the D15F37 loci and the deletion breakpoints suggests that the common deletions arise by unequal crossover events at or near these loci.
大约70%的普拉德-威利综合征或安吉尔曼综合征患者在15号染色体长臂近端区域有一个大小相似的3-4 Mb的新生缺失。远端断点似乎聚集在P基因（OCA2）和D15S24之间，而在近端一侧已鉴定出两个缺失断点簇（一个在D15S541着丝粒侧，另一个在D15S541和D15S9之间）。基于在15q11→q13中鉴定出一个基因家族（MN7，D15F37），我们之前曾提出该序列多拷贝的存在可能与该区域的不稳定性有关。使用荧光原位杂交和酵母人工染色体作图，我们发现至少一个D15F37位点在D15S9着丝粒侧，至少两个在OCA2和D15S24之间。通过cDNA克隆和序列分析确定，每个单独的位点都有表达。D15F37位点与缺失断点的紧密接近表明，常见的缺失是由这些位点或其附近的不等交换事件引起的。
