Structural organization, mapping, characterization and evolutionary relationships of CDKN2 gene family members in Xiphophorus fishes

Steven Kazianis, Vandeeta A. Khanolkar, Rodney S. Nairn, J. Douglas Rains, David Trono, Rachel Garcia, Earlanda L. Williams, Ronald B. Walter

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Xiphophorus fishes and their hybrids are used as models for the study of melanoma and other diseases. The cyclin-dependent kinase inhibitor gene family in humans is comprised of four members, including CDKN2A (P16), and dysregulation of this gene is implicated in numerous neoplasms including melanomas. We have investigated the status of the gene family in the southern platyfish X. maculatus. Xiphophorus harbors at least two such loci, which we now term CDKN2A/B and CDKN2D. Both loci map to Xiphophorus linkage group 5, a genomic area that has long been known to harbor the DIFF tumor suppressor locus. Within this report, we report on the complete cloning, genomic exon/intron boundary delineation, linkage mapping and expressional characteristics of Xiphophorus CDKN2D. We also compare and contrast this expression to that of the previously isolated CDKN2AB locus in normal and neoplastic tissues derived from non-hybrid and hybrid fishes. The hypothetical evolutionary relationships of gene family members and their involvement in melanoma is evaluated. In comparison to CDKN2A/B, the RNA expression of Xiphophorus CDKN2D differs in normal tissues and is not associated with melanotic/pathologic tissues, confirming functional divergence between obvious homologues.

Original languageEnglish (US)
Pages (from-to)291-299
Number of pages9
JournalComparative Biochemistry and Physiology - C Toxicology and Pharmacology
Volume138
Issue number3
DOIs
StatePublished - Jul 2004

Keywords

  • Cell cycle
  • INK4
  • Melanoma
  • Platyfish
  • Swordtail
  • Teleost

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

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