Transcript map and comparative analysis of the 1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid diseases with a del(5q)

Loss of a whole chromosome 5, or a del(5q), are recurring abnormalities in malignant myeloid diseases. In previous studies, we defined a commonly dele ted segment (CDS) of 1.5 Mb between D5S479 and D5S500 in patients with a de l(5q), and we established a P1 artificial chromosome-based contig encompass ing this interval. To identify candidate tumor suppressor genes (TSGs), we developed a transcript map of the CDS. The map contains 18 genes and 12 exp ressed sequence tags/UniGenes. Among the 18 genes are 10 genes that were pr eviously cloned and 8 novel genes. The newly identified genes include CDC23 , which encodes a component of the anaphase-promoting complex; RAB6KIFL, wh ich encodes a kinesin-like protein involved in organelle transport; and KLH L3, which encodes a human homologue of the Drosophila ring canal protein, k elch, We determined the intron/exon organization of 14 genes and eliminated each gene as a classical TSG by mutation analysis. In addition, we establi shed a single-nucleotide polymorphism map as well as a map of the mouse gen ome that is syntenic to the CDS of human 5q31. The development of a transcr iption map will facilitate the molecular cloning of a myeloid leukemia supp ressor gene on 5q. (C) 2001 academic Press.