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 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.
Lai
F
F
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Godley
L A
LA
Joslin
J
J
Fernald
A A
AA
Liu
J
J
Espinosa
R
R
Zhao
N
N
Pamintuan
L
L
Till
B G
BG
Larson
R A
RA
Qian
Z
Z
Le Beau
M M
MM
D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002872:Chromosome Deletion; D022222:Chromosomes, Artificial, Human; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004252:DNA Mutational Analysis; D015723:Gene Library; D016147:Genes, Tumor Suppressor; D006801:Humans; D016547:Kinesins / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020161:Physical Chromosome Mapping
D048868:Adaptor Proteins, Signal Transducing; D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; C577440:CDC23 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C410089:KIF20A protein, human; C489837:KLHL3 protein, human; D008840:Microfilament Proteins; D016547:Kinesins