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

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

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 melanom...

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Published in:Comparative biochemistry and physiology. Toxicology & pharmacology Vol. 138; no. 3; pp. 291 - 299
Main Authors: Kazianis, Steven, Khanolkar, Vandeeta A., Nairn, Rodney S., Rains, J. Douglas, Trono, David, Garcia, Rachel, Williams, Earlanda L., Walter, Ronald B.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-07-2004
Subjects:
Amino Acid Sequence
Animals
Cell cycle
Cloning, Molecular
Cyclin-Dependent Kinase Inhibitor p16 - chemistry
Cyclin-Dependent Kinase Inhibitor p16 - genetics
Cyprinodontiformes - genetics
Evolution, Molecular
Freshwater
Gene Expression Profiling
Humans
INK4
Introns - genetics
Melanoma
Molecular Sequence Data
Phylogeny
Physical Chromosome Mapping
Pisces
Platyfish
RNA, Messenger - analysis
RNA, Messenger - genetics
Sequence Alignment
Sequence Homology
Swordtail
Teleost
Xiphophorus
Teleost
Swordtail
Platyfish
INK4
Melanoma
Cell cycle
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Summary: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.
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ISSN:1532-0456
1878-1659
DOI:10.1016/j.cca.2004.08.003