title: Structural organization, mapping, characterization and evolutionary relationships of CDKN2 gene family members in Xiphophorus fishes.
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.
authors.affiliation: Molecular Biosciences Research Group, Texas State University, Dept of Chemistry and Biochemistry, San Marcos, TX, USA. skazianis@wistar.upenn.edu
authors.forename: Steven
authors.initials: S
authors.lastname: Kazianis
authors.forename: Vandeeta A
authors.initials: VA
authors.lastname: Khanolkar
authors.forename: Rodney S
authors.initials: RS
authors.lastname: Nairn
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Rains
authors.forename: David
authors.initials: D
authors.lastname: Trono
authors.forename: Rachel
authors.initials: R
authors.lastname: Garcia
authors.forename: Earlanda L
authors.initials: EL
authors.lastname: Williams
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Walter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry* / Q000235:genetics*; D003532:Cyprinodontiformes / Q000235:genetics*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment; D017385:Sequence Homology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger