Transcript map and comparative analysis of the 1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid diseases with a del(5q)
Transcript map and comparative analysis of the 1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid diseases with a del(5q)
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DOI：
10.1006/geno.2000.6414
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发表时间：
2001-01-15
期刊：
影响因子：
4.4
通讯作者：
Le Beau, MM
中科院分区：
文献类型：
--
作者：
Lai, F;Godley, LA;Le Beau, MM
在恶性髓系疾病中，丢失整个5号染色体或del(5q)是反复出现的异常。在以前的研究中，我们在D5S479和D5S500之间定义了一个1.5Mb的共同缺失片段(CDS)，并建立了围绕这一区间的基于P1人工染色体的重叠群。为了寻找候选抑癌基因(TSG)，我们开发了CDS的转录图谱。该图谱包含18个基因和12个表达序列标签/UniGenes。在这18个基因中，有10个是已克隆的基因，8个是新基因。这些新发现的基因包括CDC23，它编码后期促进复合体的一个组成部分；RAB6KIFL，它编码参与细胞器运输的激动素样蛋白；以及KLHL3，它编码果蝇环管蛋白Kelch的人类同源物。我们确定了14个基因的内含子/外显子组织，并通过突变分析排除了每个基因作为经典的TSG。此外，我们还建立了单核苷酸多态图谱以及与人类5q31的CDS同源的小鼠基因组图谱。转录图谱的建立为5q上髓系白血病抑制基因的分子克隆奠定了基础。(C)2001年学术出版社。
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. (C) 2001 academic Press.