Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2)

Zejuan Sheng, Junqi He, Joseph A. Tuppen, Wenping Sun, Zia Fazili, Elizabeth R. Smith, Feng B. Dong, Xiangxi Xu

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Disabled-2 (DAB2 for human and Dab2 for other species) is one of two mammalian orthologues of Drosophila Disabled. DAB2 exhibits properties of a tumor suppressor gene: the expression of DAB2 is eliminated in 85-95% of breast and ovarian tumors; homozygous deletions of the gene have been found in some of these tumors; and reintroduction of DAB2 expression suppresses tumorigenicity of carcinoma cells. To study the mechanisms of loss of expression and to detect possible mutations in tumors, we have investigated the genomic structure of the DAB2 gene. The complete DAB2 gene was identified and sequenced from four overlapping BAC clones found to contain the gene. Complement factor 9 (C9) gene was localized next to the DAB2 gene at the 3′-end of the BAC DNA fragments. The human DAB2 gene is about 35 kb in size and consists of 15 exons and 14 introns, producing an approximately 4-kb message. A spliced variant corresponding to mouse Dab2 p93 and a 3′-end spliced variant were also identified. The translation initiation site resides in the second exon, and the noncoding first exon is separated from the second exon by a 14-kb intron. The 420-bp sequence 5′ of exon 1 contains a CpG island (39 CpG sites). This 420-bp putative promoter was found to contain the site for transcription initiation, identified by RNase protection assay, and is sufficient for active transcription in epithelial cells. The information about the gene structure of DAB2 will enable us to analyze possible mutations and the mechanisms of loss of DAB2 expression in tumors.

Original languageEnglish
Pages (from-to)381-386
Number of pages6
JournalGenomics
Volume70
Issue number3
DOIs
StatePublished - Dec 15 2000
Externally publishedYes

Fingerprint

Sequence Analysis
Genes
Exons
Gene Expression
Introns
Complement C9
Neoplasms
Mutation
CpG Islands
Transcription Initiation Site
Gene Deletion
Ribonucleases
Tumor Suppressor Genes
Drosophila
Clone Cells
Epithelial Cells
Breast Neoplasms
Carcinoma

ASJC Scopus subject areas

  • Genetics

Cite this

Sheng, Z., He, J., Tuppen, J. A., Sun, W., Fazili, Z., Smith, E. R., ... Xu, X. (2000). Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2). Genomics, 70(3), 381-386. https://doi.org/10.1006/geno.2000.6383

Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2). / Sheng, Zejuan; He, Junqi; Tuppen, Joseph A.; Sun, Wenping; Fazili, Zia; Smith, Elizabeth R.; Dong, Feng B.; Xu, Xiangxi.

In: Genomics, Vol. 70, No. 3, 15.12.2000, p. 381-386.

Research output: Contribution to journalArticle

Sheng, Z, He, J, Tuppen, JA, Sun, W, Fazili, Z, Smith, ER, Dong, FB & Xu, X 2000, 'Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2)', Genomics, vol. 70, no. 3, pp. 381-386. https://doi.org/10.1006/geno.2000.6383
Sheng Z, He J, Tuppen JA, Sun W, Fazili Z, Smith ER et al. Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2). Genomics. 2000 Dec 15;70(3):381-386. https://doi.org/10.1006/geno.2000.6383
Sheng, Zejuan ; He, Junqi ; Tuppen, Joseph A. ; Sun, Wenping ; Fazili, Zia ; Smith, Elizabeth R. ; Dong, Feng B. ; Xu, Xiangxi. / Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2). In: Genomics. 2000 ; Vol. 70, No. 3. pp. 381-386.
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