Structural organization of the human dihydropyrimidine dehydrogenase gene

Martin R. Johnson, Kangshang Wang, Silke Tillmanns, Nicolas Albin, Robert B Diasio

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Deficiency of the pyrimidine catabolic enzyme, dihydropyrimidine dehydrogenase (DPD), has been shown to be responsible for a pharmacogenetic syndrome in which administration of 5-fluorouracil is associated with severe and potentially life-threatening toxicity. Following the recent availability of the cDNA for DPD, there were initial reports of several molecular defects (point mutations, deletions due to exon skipping) that were suggested as a potential molecular basis for DPD deficiency, even before the complete physical structure of the DPD gene was known. To understand the mechanism responsible for DPD deficiency, we have determined the genomic structure and organization of the human DPD gene. The gene is approximately 150 kb in length, and it consists of 23 exons, ranging in size from 69 to 1404 bp. The sequences of intronic regions flanking the exon boundaries have been determined. The physical map of the DPD gene should permit development of rapid assays in detect point mutations or small deletions in the DPD gene associated with 5-fluorouracil toxicity.

Original languageEnglish (US)
Pages (from-to)1660-1663
Number of pages4
JournalCancer Research
Volume57
Issue number9
StatePublished - May 1 1997
Externally publishedYes

Fingerprint

Dihydrouracil Dehydrogenase (NADP)
Dihydropyrimidine Dehydrogenase Deficiency
Genes
Exons
Point Mutation
Fluorouracil
Pharmacogenetics
Complementary DNA
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Johnson, M. R., Wang, K., Tillmanns, S., Albin, N., & Diasio, R. B. (1997). Structural organization of the human dihydropyrimidine dehydrogenase gene. Cancer Research, 57(9), 1660-1663.

Structural organization of the human dihydropyrimidine dehydrogenase gene. / Johnson, Martin R.; Wang, Kangshang; Tillmanns, Silke; Albin, Nicolas; Diasio, Robert B.

In: Cancer Research, Vol. 57, No. 9, 01.05.1997, p. 1660-1663.

Research output: Contribution to journalArticle

Johnson, MR, Wang, K, Tillmanns, S, Albin, N & Diasio, RB 1997, 'Structural organization of the human dihydropyrimidine dehydrogenase gene', Cancer Research, vol. 57, no. 9, pp. 1660-1663.
Johnson MR, Wang K, Tillmanns S, Albin N, Diasio RB. Structural organization of the human dihydropyrimidine dehydrogenase gene. Cancer Research. 1997 May 1;57(9):1660-1663.
Johnson, Martin R. ; Wang, Kangshang ; Tillmanns, Silke ; Albin, Nicolas ; Diasio, Robert B. / Structural organization of the human dihydropyrimidine dehydrogenase gene. In: Cancer Research. 1997 ; Vol. 57, No. 9. pp. 1660-1663.
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