Functional analysis of human ornithine decarboxylase alleles

Y. Guo, Robin B Harris, D. Rosson, D. Boorman, T. G. O'Brien

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

It has been known for >10 years that there are two alleles of the human ornithine decarboxylase (ODC) gene, defined by a polymorphic PstI RFLP in intron 1. We have sequenced a large portion of each of the two alleles, including some of the 5' promoter region, exon 1, intron 1, and exon 2, and determined that a single nucleotide polymorphism at base +317 (relative to transcription start site) is responsible for the presence or absence of the PstI restriction site. We have developed two genotyping assays, a PCR-RFLP assay and a high-throughput TaqMan-based method, and determined the ODC genotype distribution in >900 North American DNA samples. On the basis of its location between two closely spaced Myc/Max binding sites (E-boxes), we speculated that the single nucleotide polymorphism at base +317 could have functional significance. Results of transfection assays with allele-specific reporter constructs support this hypothesis. The promoter/regulatory region derived from the minor ODC allele (A allele) was more effective in driving luciferase expression in these assays than the identical region from the major allele (G allele). Our results suggest that individuals homozygous for the A allele may be capable of greater ODC expression after environmental exposures, especially those that up-regulate c-MYC expression.

Original languageEnglish (US)
Pages (from-to)6314-6317
Number of pages4
JournalCancer Research
Volume60
Issue number22
StatePublished - 2000

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Ornithine Decarboxylase
Alleles
Genetic Promoter Regions
Restriction Fragment Length Polymorphisms
Introns
Single Nucleotide Polymorphism
Exons
Nucleic Acid Regulatory Sequences
Transcription Initiation Site
Environmental Exposure
Luciferases
Transfection
Up-Regulation
Binding Sites
Genotype
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Guo, Y., Harris, R. B., Rosson, D., Boorman, D., & O'Brien, T. G. (2000). Functional analysis of human ornithine decarboxylase alleles. Cancer Research, 60(22), 6314-6317.

Functional analysis of human ornithine decarboxylase alleles. / Guo, Y.; Harris, Robin B; Rosson, D.; Boorman, D.; O'Brien, T. G.

In: Cancer Research, Vol. 60, No. 22, 2000, p. 6314-6317.

Research output: Contribution to journalArticle

Guo, Y, Harris, RB, Rosson, D, Boorman, D & O'Brien, TG 2000, 'Functional analysis of human ornithine decarboxylase alleles', Cancer Research, vol. 60, no. 22, pp. 6314-6317.
Guo Y, Harris RB, Rosson D, Boorman D, O'Brien TG. Functional analysis of human ornithine decarboxylase alleles. Cancer Research. 2000;60(22):6314-6317.
Guo, Y. ; Harris, Robin B ; Rosson, D. ; Boorman, D. ; O'Brien, T. G. / Functional analysis of human ornithine decarboxylase alleles. In: Cancer Research. 2000 ; Vol. 60, No. 22. pp. 6314-6317.
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