Allellic loss of the chromosome 12p is a frequent event in childhood acute lymphoblastic leukemia. This region was also found deleted in several other hematological malignancies as well as a variety of solid tumors suggesting the presence of a tumor suppressor gene. The chromosomal region containing this suppressor locus was narrowed down to a an interval of approximately 750 kb delimited by D12S98 and D12S358. As we could not identify a known candidate gene, we initiated the construction of a detailed transcription map focusing on a contig of 4 overlapping BACs. Towards this goal we applied a strategy integrating several complementary approaches: (1) Computer-based data mining tools applied to the existing genomic sequence (750 kb) derived form the BAC contig; (2) Exon amplification and EST resources to identify putative cDNAs; (3) Determination of general expression pattern by RT-PCR and Northern blotting; (4) Comparative genomic analysis with distant vertebrate species such as Fugu rubripes and Tetraodon nigroviridis. This transcript mapping strategy has identified 32 potential transcription units, including 2 known genes, 5 new genes, 9 Unigene entries and 16 other EST clusters. The region contains also 5 pseudogenes. This map should facilitate subsequent effort to characterize the candidate genes. This study is a good illustration of how the integration of genome-based approaches facilitates the identification of genes in large interval.
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Montpetit, A., Trudel, N. & Sinnett, D. A detailed transcript map of the human chromosome 12p12.3 tumor suppressor locus: the usefulness of an integrative approach. Nat Genet 27 (Suppl 4), 74 (2001). https://doi.org/10.1038/87218
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DOI: https://doi.org/10.1038/87218