Transcript Map and Comparative Analysis of the 1.5-Mb Commonly Deleted Segment of Human 5q31 in Malignant Myeloid Diseases with a del(5q)

• Published in: Genomics (San Diego, Calif.) Vol. 71; no. 2; pp. 235 - 245
• Main Authors: Lai, Fang, Godley, Lucy A., Joslin, John, Fernald, Anthony A., Liu, Jin, Espinosa, Rafael, Zhao, Nanding, Pamintuan, Leslie, Till, Brian G., Larson, Richard A., Qian, Zhijian, Le Beau, Michelle M.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.01.2001; Elsevier
• Subjects: Acute Disease; Animals; Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; Biological and medical sciences; Carrier Proteins - genetics; CDC23 gene; Cell Cycle Proteins - genetics; chromosome 5; Chromosome Deletion; Chromosomes, Artificial, Human; Chromosomes, Human, Pair 5 - genetics; DNA Mutational Analysis; Gene Library; Genes, Tumor Suppressor; Hematologic and hematopoietic diseases; Humans; kelch protein; Kinesin - genetics; KLH3 gene; Leukemia, Myeloid - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mice; Molecular Sequence Data; Myelodysplastic Syndromes - genetics; Physical Chromosome Mapping; RAB6KIFL gene; Genetic mapping; Human; Nucleotide sequence; Homology; Malignant hemopathy; Chromosome B5; Myelodysplastic syndrome; Myeloproliferative syndrome; Contig; Gene; Chronic myelocytic leukemia; Mutation; Tumor suppressor gene
• ISSN: 0888-7543; 1089-8646
• 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.