A CDKN2-like polymorphism in Xiphophorus LG V is associated with UV-B-swordtail hybrids.
The genetic basis of spontaneous melanoma formation in spotted dorsal (Sd) Xiphophorus platyfish-swordtail hybrids has been explained by a 2-gene inheritance model involving a sex-linked oncogene, Xmrk, and an autosomal tumour suppressor, DIFF. The Xmrk oncogene encodes a receptor tyrosine kinase related to EGFR; the nature of the DIFF tumour suppressor gene is unknown. In this study, the genetic basis of UV-B-induced melanoma formation was examined in closely related, spotted side platyfish-swordtail hybrids, which carry a different sex-linked pigment pattern locus, Sp. Spotted side Xiphophorus platyfish-swordtail backcross hybrids were UV-irradiated in order to induce melanomas at frequencies 6-fold higher than occur spontaneously in non-irradiated control animals. To identify genetic determinants of melanoma susceptibility in this UV-inducible Xiphophorus model, individual animals were genotyped from control and UV-irradiated experimental regimes using allozyme and DNA restriction fragment length polymorphisms and tested for joint segregation of genetic markers with pigmentation phenotype and UV-induced melanoma formation. Joint segregation results showed linkage of a CDKN2-like DNA polymorphism with UV-B-induced melanoma formation in these hybrids. The CDKN2-like polymorphism mapped to Xiphophorus linkage group V and exhibited recombination fractions with ES1 and MDH2 allozyme markers consistent with previous localization of the DIFF tumour suppressor locus. The results indicate that the CDKN2-like sequence cloned and mapped in this study is a candidate for the DIFF tumour suppressor gene. The nucleotide sequence data reported in this study were submitted to GenBank/EMBL under accession number U69273.