Gong W, Emanuel B S, Collins J, Kim D H, Wang Z, Chen F, Zhang G, Roe B, Budarf M L
The Division of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, PA, USA.
Hum Mol Genet. 1996 Jun;5(6):789-800. doi: 10.1093/hmg/5.6.789.
The majority of patients with DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS) have a microdeletion of 22q11. Using translocation breakpoints and fluorescence in situ hybridization analysis (FISH), the minimal DiGeorge critical region (MDGCR) has been narrowed to 250 kb in the vicinity of D22S75 (N25). The construction of a detailed transcription map covering the MDGCR is an essential first step toward the identification of genes important to the etiology of DGS/VCFS, two complex disorders. We have identified a minimum of 11 transcription units encoded in the MDGCR using a combination of methods including cDNA selection, RT-PCR, RACE and genomic sequencing. This approach is somewhat unique and may serve as a model for gene identification. Of the 11 transcripts, one is the previously reported DGCR2/IDD/LAN gene, and three revealed a high level of similarity to mammalian genes: a Mus musculus serine/threonine kinase, a rat tricarboxylate transport protein and a bovine clathrin heavy chain. The remaining transcripts do not demonstrate any significant homology to genes of known function. The identification of these transcription units in the MDGCR will facilitate their further characterization and help elucidate their role in the etiology of DGS/VCFS.
大多数患有迪格奥尔格综合征（DGS）和腭心面综合征（VCFS）的患者存在22q11微缺失。利用易位断点和荧光原位杂交分析（FISH），最小迪格奥尔格关键区域（MDGCR）已被缩小至D22S75（N25）附近的250 kb。构建覆盖MDGCR的详细转录图谱是鉴定对DGS/VCFS这两种复杂疾病病因至关重要的基因的关键第一步。我们使用包括cDNA筛选、逆转录聚合酶链反应（RT-PCR）、cDNA末端快速扩增（RACE）和基因组测序在内的多种方法，在MDGCR中鉴定出至少11个转录单元。这种方法具有一定独特性，可作为基因鉴定的一个模型。在这11个转录本中，一个是先前报道的DGCR2/IDD/LAN基因，另外三个与哺乳动物基因具有高度相似性：小家鼠丝氨酸/苏氨酸激酶、大鼠三羧酸转运蛋白和牛网格蛋白重链。其余转录本与已知功能的基因没有任何显著同源性。在MDGCR中鉴定这些转录单元将有助于对它们进行进一步表征，并有助于阐明它们在DGS/VCFS病因中的作用。
