Lai F, Godley L A, Joslin J, Fernald A A, Liu J, Espinosa R, Zhao N, Pamintuan L, Till B G, Larson R A, Qian Z, Le Beau M M
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Genomics. 2001 Jan 15;71(2):235-45. doi: 10.1006/geno.2000.6414.
Loss of a whole chromosome 5, or a del(5q), are recurring abnormalities in malignant myeloid diseases. In previous studies, we defined a commonly deleted segment (CDS) of 1.5 Mb between D5S479 and D5S500 in patients with a del(5q), and we established a P1 artificial chromosome-based contig encompassing this interval. To identify candidate tumor suppressor genes (TSGs), we developed a transcript map of the CDS. The map contains 18 genes and 12 expressed sequence tags/UniGenes. Among the 18 genes are 10 genes that were previously cloned and 8 novel genes. The newly identified genes include CDC23, which encodes a component of the anaphase-promoting complex; RAB6KIFL, which encodes a kinesin-like protein involved in organelle transport; and KLHL3, which encodes a human homologue of the Drosophila ring canal protein, kelch. We determined the intron/exon organization of 14 genes and eliminated each gene as a classical TSG by mutation analysis. In addition, we established a single-nucleotide polymorphism map as well as a map of the mouse genome that is syntenic to the CDS of human 5q31. The development of a transcription map will facilitate the molecular cloning of a myeloid leukemia suppressor gene on 5q.
整条5号染色体缺失或5号染色体长臂缺失（del(5q)）是恶性髓系疾病中反复出现的异常情况。在之前的研究中，我们确定了dell(5q)患者中位于D5S479和D5S500之间1.5Mb的常见缺失片段（CDS），并构建了一个包含该区间的基于P1人工染色体的重叠群。为了鉴定候选肿瘤抑制基因（TSG），我们绘制了CDS的转录图谱。该图谱包含18个基因和12个表达序列标签/单基因簇。在这18个基因中，有10个是先前克隆的基因，8个是新基因。新鉴定的基因包括编码后期促进复合体一个组分的CDC23；编码参与细胞器运输的驱动蛋白样蛋白的RAB6KIFL；以及编码果蝇环管蛋白kelch的人类同源物的KLHL3。我们确定了14个基因的内含子/外显子结构，并通过突变分析排除了每个基因作为经典肿瘤抑制基因的可能性。此外，我们建立了一个单核苷酸多态性图谱以及与人类5q31的CDS同线的小鼠基因组图谱。转录图谱的绘制将有助于5号染色体上髓系白血病抑制基因的分子克隆。
